clinical and functional outcomes for patients following rotator cuff … · cuff pathology among...
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Clinical and functional outcomes for patients following rotator cuff
repair surgery, with or without adjuvant platelet rich plasma
injections.
Jessica Anne Colliver
This thesis is presented for the degree of Master of Science of
The University of Western Australia
School of Sport Science, Exercise and Health
2015
Supervisors:
Winthrop Professor Timothy Ackland
Clinical Associate Professor Allan Wang
Doctor Brendan Joss
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ABSTRACT
Background: Tendon-bone healing following rotator cuff repair correlates with a
successful outcome. With the relatively high re-tear rates reported in the literature despite
multiple surgical and suture anchor techniques, there has been an increase in research into
biological adjuvant therapies that elevate local growth factor concentrations, to assist
structural tendon healing following rotator cuff surgery.
Purpose: To determine if postoperative and repeated application of platelet-rich plasma
(PRP) to the tendon repair site improves early tendon healing and enhances functional
recovery following double row arthroscopic supraspinatus repair. A secondary objective
was to determine if partial re-tears early post-surgery reveal differences in subjective
function, or objective isokinetic strength, compared to completely intact tendon repairs;
and if early tendon healing can be predicted using these measures, independent of medical
imaging.
Study Design: Randomised controlled trial; Level of evidence = 2.
Methods: 60 patients underwent arthroscopic, double row supraspinatus tendon repair.
Following post-surgery randomisation, 30 patients received two ultrasound-guided
injections of PRP to the repair site at 7 and 14 days post-surgery. Functional scores were
recorded pre-surgery and post-surgery, at 6, 12 and 16 weeks; and included the Oxford
Shoulder Score (OSS), the Quick Disability of the Arm, Shoulder and Hand
(QuickDASH), Visual Analogue Scale (VAS) for pain and the Short Form-12 (SF-12)
quality of life score. Isokinetic strength and active range of motion were also recorded at
16 weeks post-surgery. Early post surgery structural healing of the tendon was assessed
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with Magnetic Resonance Imaging (MRI) at 16 weeks, with cuff appearance graded
according to the Sugaya classification.
Results: PRP treatment did not improve early functional recovery, strength or range of
motion, nor influence pain scores at any time point following arthroscopic supraspinatus
repair. No difference was seen in MRI structural integrity between treatment and control
groups (p=0.35). At 16 weeks post-surgery, the PRP group had 0% full thickness tear;
23% partial tear and 77% intact, compared to the control group with 7% full-thickness
tear; 23% partial tear and 70% intact.
In the secondary study, full-thickness tears were excluded and the treatment and control
groups pooled to determine if functional and strength differences were observed between
Sugaya classified MRI groups (36% of the cohort had grade one classification; 40% grade
two; and 24% grade three). No significant differences were observed between MRI
groups for functional scores (VAS, OSS and QuickDASH) or isokinetic strength at 4
months post-surgery. Only 64% of the partial tear group, and 13% of the intact repair
group were correctly classified with five variables entered into a discriminant analysis
prediction equation.
Conclusion: Ultrasound-guided PRP injections on two occasions post-surgery does not
improve early tendon-bone healing, or functional recovery. Correct tendon healing
classification early post rotator cuff surgery must include medical imaging, and reliance
on functional scores and isokinetic strength alone to assess early tendon healing is not
supported.
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ACKNOWLEDGEMENTS
I would like to take the time to thank all of the people that have contributed to getting me
to this point. This thesis has taken me a lot longer than it should have, and I appreciate
the interest my family, friends and colleagues have taken in my progress.
Firstly to patients, who endured endless phone calls, appointments and paperwork, all in
the name of science and to help improve the post-surgery recovery for future patients.
This project would not have been possible without your invaluable contribution and
dedication, so thank you.
To each of my supervisors: Prof Tim Ackland, for your encouragement and patience,
especially towards the end of this project, provided me with the direction I needed. I am
grateful to have access to such a wealth of knowledge and experience. To Prof Allan
Wang, for the hours of time you dedicated to getting this project up and running, and
interest in the entire process. It is a privilege to have worked with such a well-respected
and talented surgeon. And to Dr Brendan Joss, for the years of support and
encouragement to continue to achieve in my professional and academic career. Thank
you for the hours of time you dedicated to answering endless questions.
I feel extremely grateful to have had the encouragement and support of my family and
friends, as well as my colleagues at Hollywood Functional Rehabilitation Clinic, thank
you to each and every one of you. Finally, to my wonderful fiancée Michael, I cannot
begin to thank you for your love and support over this past four years, especially in the
last six months while we have been in England. Thank you from the bottom of my heart.
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TABLE OF CONTENTS
CHAPTER 1: THE PROBLEM 1
Introduction 1
Statement of the Problem 2
Research Hypothesis 4
Patient Inclusion and Exclusion criteria 5
Inclusion Criteria 5
Exclusion Criteria 5
References 6
CHAPTER 2: LITERATURE REVIEW 11
Rotator Cuff Tendon Tears 11
Incidence of Rotator Cuff Tendon Tears 11
Aetiology of Rotator Cuff Tendon Tears 12
Diagnosis of Rotator Cuff Tendon Tears 14
Treatment of Rotator Cuff Tendon Tears 18
Non-surgical Treatment of Rotator Cuff Tendon Tears 18
Surgical Treatment of Rotator Cuff Tendon Tears 22
Attempts to Reduce High Rotator Cuff Tendon Re-tear Rates 30
Growth Factors Important in Tendon Healing/Regeneration 34
Platelet-rich Plasma 36
Platelet-rich Plasma and Tendon Injury 38
Platelet-rich Plasma Preparations and Rotator Cuff Tendon Repair 39
Summary 41
References 42
CHAPTER 3: PAPER 1. Do postoperative platelet-rich plasma injections
accelerate early tendon healing and functional recovery after arthroscopic
supraspinatus repair?: A randomised controlled trial. 58
Abstract 58
Introduction 60
Methods 62
Patient Selection 62
Surgical Technique 65
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Post-operative Protocol 66
Randomisation Protocol 66
Preparation of Platelet-rich Plasma 67
Outcome Assessments 68
Statistical Analysis 70
Results 70
Structural Evaluation 71
Functional Scores 72
Strength 73
Range of Motion 74
Discussion 75
Conclusions 79
References 79
CHAPTER FOUR: PAPER 2. Early postoperative repair status after
rotator cuff repair cannot be accurately classified using questionnaires of
patient function and isokinetic strength evaluation. 85
Preamble 85
References 86
Abstract 88
Introduction 90
Methods 91
Patients 91
Surgical Technique 93
Postoperative Management 94
Patient-reported Outcome (PRO) Measures 94
Isokinetic Strength Evaluation 95
Radiological Evaluation 97
Statistical Analysis 97
Results 98
Discussion 102
Conclusion 105
References 106
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APPENDICES
APPENDIX 1 University of Western Australia notification of research proposal
approval.
APPENDIX 2 University of Western Australia notification of ethics approval.
APPENDIX 3 South Metropolitan Area Health Service notification of ethics
approval.
APPENDIX 4 Study information sheet.
APPENDIX 5 Patient consent form.
APPENDIX 6 Visual Analogue Scale (VAS) for pain.
APPENDIX 7 Oxford shoulder score (OSS).
APPENDIX 8 Quick Deformities of the Arm, Shoulder and Hand (QuickDASH)
outcome measure.
APPENDIX 9 Short form-12 (SF-12) health survey.
APPENDIX 10 Manuscript accepted for publication in the American Journal of
Sports Medicine: Do postoperative platelet-rich plasma injections
accelerate healing and early functional recovery after arthroscopic
supraspinatus repair?: A randomized controlled trial.
APPENDIX 11 Manuscript accepted for publication in the Journal of Shoulder and
Elbow Surgery: Early postoperative repair status after rotator cuff
repair cannot be accurately classified using questionnaires of patient
function and isokinetic strength evaluation.
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LIST OF TABLES
CHAPTER 3.
Table 1. Group demographics with concomitant complications 66
Table 2. Sugaya classification of MRI scans of treatment groups 72
Table 3. Functional scores 73
Table 4. Group mean scores (as percentage of the contralateral, un-operated
arm) and t-test results for strength measures at 6 weeks post-
surgery. 74
Table 5. Group mean scores and t-test results for range of motion for the
operated limb at 16 weeks post-surgery. 75
CHAPTER 4.
Table 1. Group demographics with detail of concomitant procedures and
complications 93
Table 2. Mean (SD) scores for the patient-reported outcome (PRO) and
isokinetic maximal strength measure (at an angular speed of 60°/)
employed, for patients with intact (grade 1) and partial (Grade 2
and 3) supraspinatus tendon re-tears. Independent sample t-test
comparisons are provided between groups (p values). 99
Table 3. Descriptive statistics (mean ± SD) for patients with intact repairs
(grade 1) and partial (grade 2 and 3 pooled) supraspinatus tendon
re-tears. 100
Table 4 Discriminant analysis for variables predicting an intact repair
(n=21, grade 1 Sugaya classification) or partial re-tears (n=37,
grade 2 and 3 Sugaya classification). 101
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LIST OF FIGURES
CHAPTER 2.
Figure 1. Open rotator cuff repair, landmarks and incision marked
(Ghodadra, et al., 2009).
24
Figure 2. Mini-open rotator cuff repair (Ghodadra, et al., 2009). 25
Figure 3. Arthroscopic rotator cuff repair (Ghodadra, et al., 2009). 26
CHAPTER 3.
Figure 1. CONSORT (Consolidated Standards of Reporting Trials)
flowchart.
64
Figure 2. Ultrasound image of needle placement directly at the tendon
repair site (arrow).
68
Figure 3. T1-weighted coronal magnetic resonance image displaying
Sugaya grade 1 appearance.
69
CHAPTER 4.
Figure 1. A patient performing humeral (A) internal and (B) external
rotation on the Biodex Isokinetic Dynomometer
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1
CHAPTER 1
THE PROBLEM
INTRODUCTION
Rotator cuff tendon tear is one of the most common injuries of the shoulder joint
(Mitchell, et al., 2005), with a reported incidence rate ranging from 5 to 40% (Baydar, et
al., 2009) and over 250,000 rotator cuff repairs performed annually in the United States
alone (Yamaguchi et al., 2006). The prevalence of rotator cuff pathology increases with
age (Bokor, et al., 1993; Kinsella & Velkoff, 2001; Murrell & Walton, 2001), with
Yamaguchi, et al. (2006) also reporting an increase in the likelihood of bilateral rotator
cuff pathology among patients over the age of 60 years. As the population continues to
age, degenerative rotator cuff tears are likely to become an increasing problem.
Failure to heal and tendon re-tearing following rotator cuff surgery is not uncommon.
Re-tear rates have been reported as high as 90% in the radiology literature, and as high
57% in orthopaedic literature, depending on patient age, the size of the tendon tear and
level of degeneration, fatty infiltration, type of suture anchors, surgical technique and
compliance with post-surgery rehabilitation guidelines (Boileau, et al., 2005; Galatz, et
al., 2004; Gulotta & Rodeo, 2009; Sugaya, et al., 2007). It has been widely reported that
those over the age of 60 years have significantly poorer rates of healing following rotator
cuff repair surgery (Boileau, et al., 2005; DeFranco, et al., 2007; Oh, et al., 2010;
Thomazeau, et al., 1997). The absence of tendon healing and recurrent tears following
rotator cuff surgery lead to poor functional strength (Boileau, et al., 2005; Cho & Rhee,
2009; Galatz, et al., 2001; Harryman, et al., 1991).
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The goal of rotator cuff surgery is to decrease pain and improve patient function. While
the majority of patients who undergo this type of surgery see this result, there are some
who continue to experience pain and loss of function and who are left unsatisfied due to
recurrent tendon tearing or failed healing. Younger, more active patients may need to
return to employment in physical roles or even to sport. Due to the lengthy nature of
post-surgical recovery, patients often require early confirmation of tendon healing so as
to tailor their rehabilitation programs accordingly.
STATEMENT OF THE PROBLEM
Despite the advances in surgical and suture anchoring techniques to improve rotator
cuff tendon-to-bone fixation, failure of the tendon repair occurs often (Boileau, et al.,
2005; Galatz, et al., 2004; Sugaya, et al., 2005; 2007). While tendon re-tears may be
due to a specific injury at the site, it may also be caused by incomplete or failed primary
healing following rotator cuff repair surgery (Boileau, et al., 2005; Carpenter, et al.,
1998).
In a bid to improve early primary tendon healing, there has been an increase in research
effort related to the use of biological adjuvant therapies that elevate local growth factor
concentrations. In particular, many studies have investigated platelet-rich plasma (PRP)
products, where a supra physiological concentration of platelets is delivered to the
tendon-bone repair site at the time of surgery. The term “PRP” remains controversial in
the literature, as this generic terminology does not differentiate between the various
commercial products available, or their respective protocols and differing platelet
concentrations (Lopez-Vidriero, et al., 2010; Sanchez, et al., 2010), with is no current
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consensus on the actual platelet concentration required to have a clinically significant
effect (Barber, et al., 2011).
While numerous studies have been published on the topic, the success of PRP use in
improving outcomes following rotator cuff repair remains unclear. Reviewing the
related literature is complicated by variations in the tendon pathologies treated, which
range from small single tendon tears to large multi-tendon tears, concomitant use of
acromioplasty (Castricini et al., 2011; Jo et al., 2011), and the formulations of PRP
used, ranging from intra-tendon injections (Kesikburun, et al., 2013; Randelli, et al.,
2008), spray application (Randelli, et al., 2011; Ruiz-Moneo, et al., 2013) or the
incorporation of a platelet-rich fibrin matrix (PRFM) (Barber, et al., 2011; Castricini, et
al., 2010; Gumina, et al., 2012) to the tendon repair site. Another factor affecting PRP
is the timing of delivery, with the majority of studies to date using time zero delivery at
the time of surgery, with Gulotta and Rodeo (2009) stating that biological augmentation
too early in the tendon healing cascade may be ineffective.
This thesis addresses two primary questions and these have been presented as journal
manuscripts in Chapters 3 and 4. The first paper (Wang, et al., 2015) sought to
determine if injections of PRP would enhance early tendon healing and functional
recovery following double row arthroscopic supraspinatus tendon repair surgery. The
primary outcome in this study was improved early tendon healing, assessed with MRI,
and the secondary outcomes related to patient-reported shoulder function and isokinetic
shoulder strength as a measure of functional recovery.
The second paper (Colliver, et al. 2015, under review) aimed to determine if patients
with an intact repair or partial re-tear in the early stages following rotator cuff repair
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surgery display differences in common shoulder patient reported outcome measures and
isokinetic strength tests; and if early post-surgical tendon healing could be predicted
using these common clinical shoulder evaluations.
RESEARCH HYPOTHESIS
The following hypotheses were developed and tested for study 1 (Wang, et al., 2015).
1. The use of delayed and repeated PRP ultrasound-guided injections following
supraspinatus tendon repair will improve early structural tendon healing, as
assessed by MRI, when compared to no PRP treatment.
2. The use of delayed and repeated PRP ultrasound-guided injections following
supraspinatus tendon repair will improve early patient-reported shoulder
function and isokinetic shoulder strength, compared to no PRP treatment.
In study 2 (Colliver, et al., under review), the following hypotheses were developed and
tested.
1. Following supraspinatus repair, differences in patient shoulder function and
isokinetic shoulder strength will be detected in those patients with partial tendon
re-tears or high MRI signal intensity, compared to those with intact repairs at 4
months post-surgery, regardless of their initial PRP group allocation.
2. Following supraspinatus repair, patients with partial re-tears and incomplete
healing can be predicted on the basis of patient function and strength tests alone,
without the need for post-surgery imaging.
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PATIENT INCLUSION AND EXCLUSION CRITERIA
The methodology for each of the papers is contained in the relevant sections of the
journal manuscripts shown in Chapters 3 and 4. However, journal papers are limited by
strict word counts, which do not allow for a full description of patient selection criteria,
or data collection and analysis methods. Therefore, a complete list of patient selection
criteria is presented here.
Inclusion Criteria
1. Patients were male or female, aged between 25-80 years.
2. Full-thickness, symptomatic tear of supraspinatus tendon as identified by
preoperative imaging and confirmed by arthroscopic evaluation.
3. Patients agreed to wear a dedicated arm sling for 4-6 weeks, as directed by the
surgeon.
4. Patients needed to be in a non-dependent relationship.
Exclusion Criteria
1. Previous history of rotator cuff repair surgery.
2. Rotator cuff tears secondary to fracture.
3. Concomitant labral tear or significant degenerative glenohumeral osteoarthritis.
4. Contralateral shoulder symptoms.
5. Prior PRP injections.
6. Non-surgical rotator cuff associated treatment in the 1 month prior to surgery,
including corticosteroid injection and anti-inflammatory treatment.
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7. Presence of rheumatalogical, neuromuscular or autoimmune disease.
8. Pre-existing conditions associated with upper extremity pain, including arthritis,
ongoing infection, carpal tunnel syndrome, cervical disc herniation, cervical
neuropathy or other nerve pathology.
9. Metabolic bone or blood disorders that could impair bone or soft tissue function.
10. Ongoing workers’ compensation claims.
11. Contraindication to postoperative MRI evaluation.
12. Likely problems with follow-up (i.e. patients with no fixed address, reported
plan to move out of town, uncooperative or patients without adequate family
support).
13. Patients who were participating in an existing ongoing trial that would interfere
with assessment of the primary or secondary outcomes.
14. Patients who did not read or speak English.
REFERENCES
Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing
influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the
Journal of Arthroscopic and Related Surgery, 27(8), 1029-1035.
Baydar, M., Akalin, E., El, O., Gulbahar, S., Bircan, C., Akgul, O., et al. (2009). The
efficacy of conservative treatment in patients with full-thickness rotator cuff
tears. Rheumatol Int, 29(6), 623-628.
Boileau, P., Brassart, N., Watkinson, D. J., Carles, M., Hatzidakis, A. M., & Krishnan,
S. G. (2005). Arthroscopic repair of full-thickness tears of the supraspinatus:
does the tendon really heal? Journal of Bone and Joint Surgery (Am), 87(6),
1229-1240.
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Bokor, D. J., Hawkins, R. J., Huckell, G. H., Angelo, R. L., & Schickendantz, M. S.
(1993). Results of nonoperative management of full-thickness tears of the rotator
cuff. Clin Orthop Relat Res(294), 103-110.
Carpenter, J. E., Thomopoulos, S., Flanagan, C. L., De Bano, C. M., & Soslowsky, L. J.
(1998). Rotator cuff defect healing: a biomechanic and histologic analysis in an
animal model. Journal of Shoulder and Elbow Surgery, 7(6), 599-605.
Castricini, R., Longo, U. G., De Benedetto, M., Panfoli, N., Pirani, P., Zini, R., et al.
(2010). Platelet-rich augmentation for arthroscopic rotator cuff repair: a
randomised control trial. Am J Sports Med, 39(2), 258-265.
Castricini, R., Longo, U. G., De Benedetto, M., Panfoli, N., Pirani, P., Zini, R., et al.
(2011). Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a
randomized controlled trial. Am J Sports Med, 39(2), 258-265.
Cho, N. S., & Rhee, Y. G. (2009). The factors affecting the clinical outcome and
integrity of arthroscopically repaired rotator cuff tears of the shoulder. Clin
Orthop Surg, 1(2), 96-104.
Colliver, J., Wang, A., Koh, E., Joss, B., Ebert, J., Ackland, T., et al. (2015). Early
post-operative repair status after rotator cuff repair cannot be classified
using questionnaires of patient function and isokinetic strength evalualtion.
Journal of Shoulder and Elbow Surgery (under review).
DeFranco, M. J., Bershadsky, B., Ciccone, J., Yum, J. K., & Iannotti, J. P. (2007).
Functional outcome of arthroscopic rotator cuff repairs: a correlation of
anatomic and clinical results. Journal of Shoulder and Elbow Surgery, 16(6),
759-765.
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Galatz, L. M., Ball, C. M., Teefey, S. A., Middleton, W. D., & Yamaguchi, K. (2004).
The outcome and repair of completely arthroscopically repaired large and
massive rotator cuff tears. Journal of Bone and Joint Surgery (Am), 86(2), 219-
224.
Galatz, L. M., Griggs, S., Cameron, B. D., & Iannotti, J. P. (2001). Prospective
longitudinal analysis of postoperative shoulder function : a ten-year follow-up
study of full-thickness rotator cuff tears. J Bone Joint Surg Am, 83-A(7), 1052-
1056.
Gulotta, L. V., & Rodeo, S. A. (2009). Growth factors for rotator cuff repair. Clinical
Sports Medicine, 28, 13-23.
Gumina, S., Campagna, V., Ferrazza, G., Giannicola, G., Fratalocchi, F., Milani, A., et
al. (2012). Use of platelet-leukocyte membrane in arthroscopic repair of large
rotator cuff tears: a prospective randomized study. J Bone Joint Surg Am,
94(15), 1345-1352.
Harryman, D. T., 2nd, Mack, L. A., Wang, K. Y., Jackins, S. E., Richardson, M. L., &
Matsen, F. A., 3rd. (1991). Repairs of the rotator cuff. Correlation of functional
results with integrity of the cuff. J Bone Joint Surg Am, 73(7), 982-989.
Jo, C. H., Kim, J. E., Yoon, K. S., Lee, J. H., Kang, S. B., Han, H. S., et al. (2011).
Does platelet-rich plasma accelerate recovery after rotator cuff repair? A
prospective cohort study. Am J Sports Med, 39(10), 2082-2090.
Kesikburun, S., Tan, A. K., Yilmaz, B., Yasar, E., & Yazicioglu, K. (2013). Platelet-
rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a
randomized controlled trial with 1-year follow-up. Am J Sports Med, 41(11),
2609-2616.
Kinsella, K., & Velkoff, V. A. (2001). An ageing world: 2001.
9
Lopez-Vidriero, E., Goulding, K. A., Simon, D. A., Sanchez, M., & Johnson, D. H.
(2010). The use of platelet-rich plasma in arthroscopy and sports medicine:
optimizing the healing environment. Arthroscopy: The Journal of Arthroscopic
and Related Surgery, 26(2), 269-278.
Mitchell, C., Adebajo, A., Hay, E., & Carr, A. (2005). Shoulder pain: diagnosis and
management in primary care. BMJ, 331(7525), 1124-1128.
Murrell, G. A., & Walton, J. R. (2001). Diagnosis of rotator cuff tears. Lancet,
357(9258), 769-770.
Oh, J. H., Kim, S. H., Kang, J. Y., Oh, C. H., & Gong, H. S. (2010). Effect of age on
functional and structural outcome after rotator cuff repair. Am J Sports Med,
38(4), 672-678.
Randelli, P., Arrigoni, P., Ragone, V., Aliprandi, A., & Cabitza, P. (2011). Platelet rich
plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year
follow-up. J Shoulder Elbow Surg, 20(4), 518-528.
Randelli, P. S., Arrigoni, P., Cabitza, P., Volpi, P., & Maffulli, N. (2008). Atologous
platelet-rich plasmafor arthroscopic rotator cuff repair. A pilot study. Disability
and Rehabilitation, 30(20-22), 1584-1589.
Ruiz-Moneo, P., Molano-Munoz, J., Prieto, E., & Algorta, J. (2013). Plasma rich in
growth factors in arthroscopic rotator cuff repair: a randomized, double-blind,
controlled clinical trial. Arthroscopy, 29(1), 2-9.
Sanchez, M., Anitua, E., & Andia, I. (2010). Poor standardization in platelet-rich
therapies hampers advancement. Arthroscopy, 26, 725-726.
Sugaya, H., Maeda, K., Matsuki, K., & Moriishi, J. (2005). Functional and structural
outcome after arthroscopic full-thickness rotator cuff repair: single-row versus
dual-row fixation. Arthroscopy, 21(11), 1307-1316.
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Sugaya, H., Maeda, K., Matsuki, K., & Moriishi, J. (2007). Repair integrity and
functional outcome after arthroscopic double-row rotator cuff repair. A
prospective outcome study. J Bone Joint Surg Am, 89(5), 953-960.
Thomazeau, H., Boukobza, E., Morcet, N., Chaperon, J., & Langlais, F. (1997).
Prediction of rotator cuff repair results by magnetic resonance imaging. Clin
Orthop Relat Res(344), 275-283.
Wang, A., McCann, P., Colliver, J., Koh, E., Ackland, T., Joss, B., et al. (2015). Do
Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing
and Functional Recovery After Arthroscopic Supraspinatus Repair? A
Randomized Controlled Trial. Am J Sports Med (in press).
Yamaguchi, K., Ditsios, K., Middleton, W. D., Hildebolt, C. F., Galatz, L. M., &
Teefey, S. A. (2006). The demographic and morphological features of rotator
cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone
Joint Surg Am, 88(8), 1699-1704.
11
CHAPTER 2
REVIEW OF LITERATURE
ROTATOR CUFF TENDON TEARS
Full thickness rotator cuff tendon tear is one of the most common injuries affecting the
shoulder joint (Mitchell, et al., 2005; Seitz, et al., 2011), with the incidence rate ranging
from 5 to 40% of the general population (Baydar, et al., 2009; Gialanella & Prometti,
2011). Those with rotator cuff tears can experience pain and decreased functional ability
(Ainsworth & Lewis, 2007; MacDermid, et al., 2004), reduction of range of motion
(ROM) in the glenohumeral joint and muscular atrophy (Maniscalco, et al., 2008;
Mitchell, et al., 2005); having an impact on health-related quality of life (MacDermid, et
al., 2004). Reduced function may include difficulty or inability to dress independently,
attending to personal hygiene and using utensils to eat. The pain can be so severe that
the patient’s sleep is also affected (Ainsworth & Lewis, 2007).
Incidence of rotator cuff tendon tears
True prevalence of rotator cuff tears is difficult to determine in the general population, as
a tendon tear can cause significant pain, weakness and disability in some, whereas others
experience little to no pain or disability (Ainsworth & Lewis, 2007; Fehringer, et al.,
2008; Gialanella & Prometti, 2011). As a result, reported incidence of rotator cuff tendon
tears varies widely throughout the literature.
Cadaveric studies have demonstrated the incidence of rotator cuff tendon tears in subjects
aged over 60 years to be at least 30%, compared with 6% in those younger than 60 years
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(Kinsella & Velkoff, 2001; Lehman, et al., 1995). Tempelhof, et al. (1999) investigated
the prevalence of rotator cuff tears in asymptomatic shoulders, and found that of a total
411 subjects, 96 (23.4%) had a full-thickness rotator cuff tear. Sher, Uribe, Posada,
Murphy and Zlatkin (1995) conducted a prospective study investigating the prevalence
of rotator cuff tendon tears in asymptomatic individuals of varying ages, with varying
activities. More than half (54%) of the cohort over the age of 60 years had either a partial
or full thickness rotator cuff tear, confirming age-related changes of the rotator cuff
consistent with other studies, identified with MRI.
The incidence of degenerative rotator cuff tendon tears increases with age, even in the
asymptomatic population (Boileau, et al., 2005; Bokor, et al., 1993; Cheung, et al., 2010;
Oh, et al., 2010; Tempelhof, et al., 1999). A study conducted by Murrell and Walton
(2001) found that rotator cuff tear frequency increased linearly with age from 30 years
(increasing from 33% in the 40s to 55% the in 50s). As the ageing population continues
to increase worldwide, degenerative rotator cuff tendon tears will become more prevalent
in the future.
Aetiology of rotator cuff tendon tears
A tendon is a tough band of fibrous connective tissue, usually connecting muscle to bone,
and capable of withstanding tension loads (Del Buono, et al., 2011; Nontarnicola &
Moretti, 2012). Tendons are often subjected to tendinopathies, as a result of trauma and
overuse, which may lead to inflammation and degeneration of the tendon and, in turn, to
a tendon tear or rupture (Notarnicola & Moretti, 2012). While most tendons have the
ability to heal following injury, the repair tissue is functionally inferior to that of normal
healthy tendon, and carries with it an increased risk of further injury .
13
Factors causing rotator cuff tendinopathies and tendon tears have traditionally been
described as extrinsic, intrinsic or a combination of the two (Seitz, et al., 2011). Extrinsic
factors are those causing compression of the rotator cuff tendons due to narrowing of the
subacromial space (Carpenter, et al., 1998; Mishra, et al., 2009), and can be related to
anatomical and/or biomechanical factors (Seitz, et al., 2011). Anatomical factors that can
contribute to the narrowing of the subacromial space include variations in the acromion
shape, orientation of the slope or angle of the acromion, or ossification of the inferior
aspect of the acromioclavicular joint or coracoacromial ligament (Seitz, et al., 2011).
Biomechanical factors may also contribute to extrinsic compression and can include
abnormal scapular and humeral kinematics, abnormalities in posture, muscular deficits
and soft tissue tightness (Seitz, et al., 2011). Intrinsic factors that affect the rotator cuff
tendons result in degeneration of the tendons caused by the natural ageing process,
decreased vascularity and blood flow (Mishra, et al., 2009), altered biology and
fibrocartilagenous changes (Carpenter, et al., 1998) associated with previous tendon
damage, and tensile tissue overload (Seitz, et al., 2011).
Although rotator cuff tears can occur as a result of an acute injury, most tears result from
gradual degeneration of the tendon and tendon-to-bone interface (Bokor, et al., 1993;
Cheung, et al., 2010). Chronic tendon tears are known to induce structural changes within
the tendon (fibro-vascular scar tissue forms during the healing process) (Anitua, et al.,
2005), rendering the tendon prone to re-tearing, as well as muscular atrophy (Liem,
Lichtenberg, et al., 2007).
Rotator cuff tendon tears can be caused by degeneration and overuse with repetitive
extrinsic compression, eccentric overload of the tendon, or by differential strains being
14
placed on the tendon (Millett, et al., 2006). Reilly and colleagues (2003) found that in
cadaveric shoulders, maximal differential strain was reached at approximately 120
degrees of shoulder abduction. Partial tears can also create tension overload in the
remaining tendon, which may increase the force concentration in the remainder of the
tendon tissue and over time, can lead to complete full-thickness rotator cuff tendon tear
(Millett, et al., 2006). While the rotator cuff tendons are able to tolerate huge tensile
stresses, compressive and sheer forces are poorly tolerated (Millett, et al., 2006).
Diagnosis of rotator cuff tendon tears
Rotator cuff pathologies are a major cause of shoulder pain. Ostor, et al., 2005 reported
that rotator cuff tendinopathy was present in 85% of patients presenting with shoulder
pain to a general medical practice. Rotator cuff tendon tears may account for up to 50%
of major shoulder injuries and, while clinical testing is the recommended first line
investigation (Beaudreuil, et al., 2009), an accurate diagnosis can be difficult with clinical
tests alone (Ainsworth & Lewis, 2007; Hughes, et al., 2008; Murrell & Walton, et al.,
2001). Investigative techniques such as magnetic resonance imaging (MRI) or ultrasound
(US) are commonly used to confirm or dismiss the presence of a rotator cuff tear (Bennell,
et al., 2007; Codsi, et al., 2014; Kluger, et al., 2011; Liem, Lichtenberg, et al., 2007;
Teefey, et al., 2004).
The diagnostic accuracy of common clinical tests for rotator cuff pathology has been
questioned in a number of reviews (Hughes, et al., 2008; Mitchell, et al., 2005; Murrell
& Walton, 2001). A clinical review conducted by Mitchell and colleagues (2005) of the
diagnosis and management of shoulder pain suggested that clinical investigation and
diagnosis should take into account the patient’s history (e.g. onset of pain, age, pain
15
during active and/or passive movements or at rest, patient’s occupation) as well as a
physical examination (palpation of the shoulder joints, comparison of power, stability and
ROM in both shoulders – active, passive and resisted, look for painful abduction arc and
the “drop arm test” where the patient lowers an abducted arm to the waist slowly; a
positive test result is indicated by the inability to hold the arm at 90 degrees of abduction,
or a patient’s inability to smoothly control the lowering of their arm). Patients presenting
with rotator cuff pathologies may have muscle wastage, active and resisted arm
movements are usually painful and often partially restricted (Mitchell, et al., 2005). And
while passive ROM may be full, it is usually painful, and history is a strong indicator;
young people often present following a traumatic incident, with atraumatic presentation
common among the elderly (Mitchell, et al., 2005). Mitchell and colleagues (2005) also
suggested that partial tears can be difficult to differentiate from rotator tendinopathy upon
physical examination, as weakness during resisted movement can occur with either
condition. The authors stated that the “drop arm test”, can be used to detect a large or
complete tear.
In a bid to improve the clinical diagnosis of rotator cuff tears, Murrell and Walton (2001)
conducted a prospective study to determine if any of 23 clinical tests commonly used in
assessment of the shoulder were predictive of a rotator cuff tear. They found that most
clinical tests could not distinguish between the group that had rotator cuff tears (partial
or full thickness tears and no other major shoulder pathology) and those with a shoulder
pathology not involving a rotator cuff tear. However, the researchers did find that three
clinical features were more positive in patients with tears and were predictors for this
condition. These were supraspinatus weakness, weakness in external rotation and
impingement. It was suggested that the “drop arm” test was also a predictor of a rotator
cuff tear due to its high specificity, however, it had a low sensitivity within the tear group.
16
These results show that patients presenting with these three clinical features, or with a
positive test for two of the three and who are over 60 years of age, there is a 98% chance
of having a rotator cuff tear. If only one of those three tests is positive, the result is
inconclusive and further imaging is required to confirm the diagnosis.
A systematic review conducted by Hughes, et al. (2008) of the diagnostic accuracy of
clinical tests for rotator cuff pathology suggested that most tests cannot be recommended
for clinical use. At best, suspicion may be heightened by positive palpitation, combined
Hawkins/painful arc/infraspinatus, among others; and suspicion may be reduced upon
negative palpation, empty can or Hawkins-Kennedy test. It has also been suggested that
the poor accuracy of common clinical tests for diagnosis of rotator cuff pathology and
tears may be attributed to the lack of anatomical validity of the tests, or that the complex
relationships of the shoulder structures make it difficult to identify specific pathologies
(Ainsworth & Lewis, 2007; Hughes, et al., 2008), highlighting the importance of medical
imaging in conjunction with clinical investigations.
US and MRI are non-invasive techniques used widely to identify rotator cuff tears and
tear size (Codsi, et al., 2014; Ianotti, et al., 2005; Kluger, et al., 2011; Naqvi, et al., 2009;
Seibold, et al., 1999; Teefey, et al., 2004). Assessment of the rotator cuff using US was
first published in 1979 (Seltzer, et al.) , and 1986 for MRI (Kneeland et al.). Initially,
there was a great variety of results in the detection of rotator cuff tears with US (Brandt,
et al., 1989), which was thought to be due to the limited experience of examination
procedures and use of low frequency transducers (Naqvi, et al., 2009; Teefey, et al.,
2004). As a result, MRI became the “gold standard” technique for diagnosis of partial
and full thickness rotator cuff tears, due to its high sensitivity and accuracy, despite the
relatively high cost (Iannotti, et al., 1991; Naqvi, et al., 2009). More recently though,
17
technical improvements and increased experience have led to a significant improvement
in US reliability (Teefey, et al., 2004).
A number of studies have re-evaluated the accuracy of both US and MRI in the detection
of partial and full rotator cuff tendon tears with modern equipment, standardised
techniques and imaging diagnostic criteria. Teefey, et al. (2004) found the overall
accuracy of diagnosing full thickness, partial thickness and intact rotator cuff tendons was
87%. Naqvi, et al. (2009) evaluated the accuracy of US and MRI in detection of full
thickness rotator cuff tears, with the overall accuracy of US being repeated as 89%,
compared with 80% for MRI. Codsi, et al. (2014) suggested US was comparable to MRI
when evaluating rotator cuff integrity, and that post-surgical US results should be
compared with MRI results for a period of time before relying solely on US for diagnosis.
Ardic, et al. (2006) however, reported MRI to be superior to US, while reported that US
was not a reliable tool for diagnosing full-thickness rotator cuff tears. Sonnabend, et al.
(1997) reported on the accuracy of US in diagnosing full thickness rotator cuff tears and
as a “useful adjunct” to the diagnosis of partial tears; however they also noted it was
operator-dependent.
18
TREATMENT OF ROTATOR CUFF TENDON TEARS
The optimal treatment for rotator cuff tears, particularly large tears, varies for each
patient. Decisions on how to treat patients should take into account the severity of
symptoms, patient functional requirements, and the presence of any concomitant diseases
that could complicate treatment (Gialanella & Prometti, 2011). The treatment for rotator
cuff tendon degeneration and injury ranges from conservative to surgical treatment.
Non-surgical treatment of rotator cuff tendon tears
Conservative treatments include exercise, physiotherapy (electrotherapy, ultrasound,
acupuncture and taping) and injection therapy (steroidal and non-steroidal) (Ainsworth &
Lewis, 2007; Lewis, 2010; Ruotolo & Nottage, 2002). Exercise or other conservative
treatment is often offered as the initial management approach, as satisfactory results
cannot be guaranteed with surgical intervention (Ainsworth & Lewis, 2007; Gialanella &
Prometti, 2011). The goals of non-surgical management of a rotator cuff tendon tear are
to eliminate pain and restore function (Ainsworth & Lewis, 2007; Millett, et al., 2006),
however, recommendations vary on the length of time conservative care should be
undertaken before seeking a surgical opinion (Ainsworth & Lewis, 2007; Itoi & Tabata,
1992).
Reviews of interventions for rotator cuff pathologies suggest that exercise may be an
effective treatment (Ainsworth & Lewis, 2007; Kuhn, 2009). Both Brox et al. (1999) and
Haahr et al. (2005) reported active physiotherapy to be superior to a placebo or control.
Physiotherapy aims to decrease shoulder pain and disability by improving joint
biomechanics and movement patterns, rather than treating the pathology, using a range
19
of modalities (Bennell, et al., 2007). Both exercise and physiotherapy are often used in
combination to treat rotator cuff tendon tears.
There is currently no consensus view on the ideal exercise or physiotherapy program for
patients with rotator cuff tendon pathologies. Many rehabilitation protocols in the
literature are based on empirical clinical evidence, which indicate a specific exercise or
activity progression based on tendon healing timelines (Millett, et al., 2006). An
evaluation-based protocol not only takes into account healing timelines, but also the
attainment of specific clinical goals, before progressing exercises (Millett, et al., 2006).
This makes good sense, considering patients with rotator cuff tendon tears do not all
progress through their rehabilitation phases at the same rate. Guidance as to the most
appropriate exercise treatment (including intensity, duration and frequency) remains
speculative (Ainsworth & Lewis, 2007).
Lewis (2010) suggested exercises that reduce superior migration of the humeral head may
be beneficial, as well as a graduated program of tendon reloading, including concentric,
isometric and eccentric exercises, in a pain-free manner. Millett and colleagues (2006)
discuss exercise rehabilitation of both partial and full-thickness tears of the rotator cuff.
Rehabilitation goals of both are to re-establish full range of motion, synchronise the firing
of the rotator cuff and periscapular muscles, and re-establish normal glenohumeral and
scapulothoracic kinematics. A graduated strength program was suggested by Ruotolo
and Nottage (2002); once shoulder pain has been controlled, focusing of scapular
stabilisation and removing deltoid work until pain is completely diminished. Range of
motion was observed to increase following a carefully designed exercise program,
however strength using manual testing remained unchanged (Bokor, et al., 1993; Itoi &
Tabata, 1992; Ruotolo & Nottage, 2002).
20
While physiotherapy is one of the most commonly prescribed conservative treatments of
rotator cuff pathology, there appears to be little evidence to support its effectiveness, with
many trials treating a single modality rather than multiple modalities; despite being the
most common way to treat shoulder pathologies in clinical practice (Bennell, et al., 2007).
The lack of consensus of this treatment is most likely due to the lack of good quality,
randomised controlled trials available in the literature focusing on clinical outcomes.
Corticosteroids are often prescribed for rotator cuff tears (Gialanella & Prometti, 2011),
however, evidence of the effectiveness of steroid injections for rotator cuff pathologies
is unconvincing, despite extensive research in this area (Ekeberg, et al., 2009; Gialanella
& Prometti, 2011). Therapeutic mechanisms of corticosteroid injections may include
anti-inflammatory effects, relaxation of reflex muscle spasm, influence on local tissue
metabolism, pain relief, mechanical improvements and placebo effect (Neustadt, 1991).
Research conducted by Bokor, et al. (1993) and Koubaa, et al. (2006) in patients with
rotator cuff tears showed positive results when treated with a combination of
rehabilitation, anti-inflammatories and local corticosteroid injections. Similarly,
Yamada, et al. (2000) saw improvements in pain, muscular strength and ROM in those
treated with conservative measures, including corticosteroids. Shibata, et al. (2001) also
showed pain relief in patients with rotator cuff tears. A recent study conducted by
Gialanella and Prometti (2011) demonstrated that patients receiving local corticosteroid
injections and rehabilitation had pain relief when compared to those with rehabilitation
alone. However, Darlington and Coomes (1977) found that while patients with
supraspinatus tendon tears had some relief from pain with local corticosteroids, there was
21
no improvement in ROM or the painful arc; concluding there was no objective evidence
that corticosteroids improve the condition.
Some studies reported that there is no reliable proof to suggest that corticosteroids
injected at the peritendinous level had adverse effects (Nichols, 2005; Paavola et al.,
2002); with Bhatia, et al. (2009) concluding that the use of corticosteroids should not be
considered a cause of rotator cuff tendon tears. Despite the suggestion of positive results
of steroid injections in conjunction with other therapies, subacromial and intra-articular
injections of corticosteroids remains controversial, with respect to it deleterious effects.
Tillander, et al. (1999) showed that after five corticosteroid injections into the
subacromial space of rats there was focal inflammation, necrosis and fragmentation of
collagen bundles, but no change was seen after three injections. Studies have reported
that intraarticular steroid injections had adverse effects on cartilage and tendons, and
osteoarthritic changes and tendon tears have been observed (Stannard & Bucknell, 1993;
Tillander, et al., 1999).
Mitchell (2005) suggests subacromial corticosteroids should be considered for short term
pain relief and to facilitate rehabilitation. Smidt et al. (2002) showed that in patients with
lateral epicondylitis, corticosteroid injections are merely the best treatment option in the
short term, compared to a physiotherapy and “wait-and-see” policy, however poor results
were reported after the 12 week follow-up. Similar results were found by Verhaar, et al.
(1996) and Hay, et al. (1999). It is thought that this could be due to the intratendinous
injection causing permanent adverse changes within the structure of the tendon, and that
patients may tend to overuse the arm following injection because they have experienced
pain relief (Peerbooms, et al., 2010; Smidt, et al, 2002).
22
Patient satisfaction with non-operative treatment of rotator cuff tears has been reported
widely in the literature with varied results; Itoi and Tabata (1992) reported 82%, Bokor,
et al. (1993) 56% and Bartolozzi, et al. (1994) 25% satisfaction. While partial-thickness
tears of the rotator cuff can usually be treated successfully with non-surgical
interventions, full-thickness tears treated non-surgically provide inconsistent and often
unacceptable results, with Millet and colleagues (2006) suggesting there are no reliable
methods of predicting successful treatment of these full-thickness tears. Bartolozzi, et al.
(1994) suggest that of patients with full thickness rotator cuff tears with symptoms for
more than 1 year, only 13% reported a satisfactory end result with non-surgical treatment.
A review conducted by Downie and Miller (2012) comparing non-operative and operative
treatment of rotator cuff tears in older patients (mean age of 60 years) was unable to find
sufficient evidence to recommend treatment. And while the reviewed studies reported
favourable operative outcomes, there was a lack of good quality non-operative treatment
studies in this age group for comparison; highlighting a gap in the research for this age
group.
Surgical treatment of rotator cuff tendon tears
Rotator cuff repair surgery is one of the most common orthopaedic procedures, with over
250,000 performed annually in the United States (Castricini, et al., 2010; Gulotta &
Rodeo, 2009). The procedure is generally offered for the painful rotator cuff that has
failed non-surgical treatment (Castricini, et al., 2010; Millett, et al., 2006). Surgery can
include a rotator cuff tendon repair with or without subacromial decompression
(Ainsworth & Lewis, 2007); and in more severe cases where osteoarthritis is involved,
shoulder joint replacement may be the only solution (Ainsworth & Lewis, 2007). The
goal of this type of surgery is to eliminate pain and improve shoulder function with
23
increased strength and ROM of the shoulder (Boissonault, et al., 2007; Ghodadra, et al.,
2009).
Optimal repair of the rotator cuff requires high fixation strength, minimal gap formation,
maintenance of mechanical stability under cyclic loads, and proper healing of the tendon
to the bone (Ghodadra, et al., 2009). The majority of studies reported excellent outcomes
following rotator cuff tendon repair surgery, with the integrity of repair generally being
shown to have a negative correlation with age (Boileau, et al., 2005; DeFranco, et al.,
2007; Ghodadra, et al., 2009; Oh, et al., 2010; Thomazeau, et al., 1997). However,
healing of the repair is also dependent on the number of tendons involved and the pre-
surgery tear size (Barber, et al., 2011). Cofield (1985) reviewed published results of open
rotator cuff repair, noting an average pain relief of 87%; ranging between 71% to 100%,
and a patient satisfaction rate of 77%.
In the past 15 years, the surgical treatment for rotator cuff tears has evolved from the
traditional open procedure, to a mini-open (arthroscopic-assisted) technique, to an all-
arthroscopic technique (Nho, et al., 2007). The traditional open approach was associated
with severe early post-operative pain, deltoid detachment and/or weakness, and
arthrofibrosis (Bennett, 2003a; 2003b; Bigliani, et al., 1992; Nho, et al., 2007). The mini-
open repair technique was developed with the potential advantage of less deltoid
morbidity, while demonstrating outcomes that were similar to those with the open
procedure (Levy, et al., 1990; Liu & Baker, 1994; Nho, et al., 2007; Paulos & Kody,
1994). More recently, surgeons are performing complete arthroscopic rotator cuff
repairs, with potential advantages including less pain, more rapid rehabilitation, the
ability to treat intra-articular lesions, smaller skin incisions, less soft tissue dissection and
a very low risk of deltoid detachment (Nho, et al., 2007). This technique has shown
24
promising results in both the short and long term (Bennett, 2003a; Galatz, et al., 2004;
Galatz, et al., 2001; Gartsman, 2001). Despite these advantages, the procedure is
technically demanding and requires a large amount of practice for the surgeon to be
proficient in this procedure (Nho, et al., 2007; Norberg, et al., 2000). Due to the technical
demands of the arthroscopic approach, a large number of orthopaedic surgeons favour the
mini-open procedure (Yamaguchi, et al., 2003).
The first documented rotator cuff repair was performed by Dr Codman, in 1911, using an
open technique, and further modifications to this technique were proposed by Neer in
1972 (Yamaguchi, et al., 2003). With an open rotator cuff repair approach, the patient is
placed in the “beach-chair” position, and a 3-6 cm incision is made parallel to the lateral
border of the acromion, in line with Langer’s lines (Figure 1). The deltoid is taken off
the anterior aspect of the acromion, usually beginning at the acromioclavicular joint,
extending along the anterior border of the acromion, then splitting the deltoid laterally 3-
5 cm. Following rotator cuff repair, the deltoid is reattached to the acromion, and the
longitudinal split of the deltoid repaired. Deltoid dysfunction has been a reported
complication with this surgical approach.
Figure 1. Open rotator cuff repair, landmarks and incision marked (Ghodadra, et al.,
2009).
25
Levy and colleagues (1990) described an arthroscopically assisted repair, where
arthroscopy was used to form a subacromial decompression and avoid deltoid takedown.
To perform the mini-open repair the arthroscopic portal is extended by 1-2 cm and the
deltoid fibres are split in line to obtain access to the repair site (Figure 2).
Figure 2. Mini-open rotator cuff repair (Ghodadra, et al., 2009).
An all-arthroscopic procedure requires only a small incision for insertion of several
cannulas 7-8 mm in diameter, and the only disruption to the deltoid is from insertion of
the cannula, as no tissue retraction is required. Following identification of the appropriate
anatomical landmarks, all arthroscopic portals are marked (Figure 3). Various surgical
instruments can be introduced through these portals into the shoulder to immobilise the
cuff, implant suture anchors and tie arthroscopic knots to hold the tendon to the bone.
26
Figure 3. Arthroscopic rotator cuff repair (Ghodadra, et al., 2009).
In addition to the surgical approach, much research has centred around suture anchoring
technique to establish a normal rotator cuff footprint (anatomic contact area between the
tendon and the bone of the humeral greater tuberosity) in order to optimise healing
potential and increase the mechanical strength of the primary fixation of the tendon repair
(Lo & Burkhart, 2003; Milano, et al., 2008). While excellent clinical results of
arthroscopic rotator cuff repair have been documented (Bennett, 2003a, 2003b;
DeFranco, et al., 2007; Kasten, et al., 2011; Liem, Bartl, et al., 2007), there has been
criticism of suture anchor repair techniques and repair integrity (Kim et al., 2006; Lo &
Burkhart, 2003). In the past, most arthroscopic rotator cuff repairs were done with a
single row of suture anchors, to anchor the free edge of the tendon to the bone (Milano,
et al., 2008). Imaging studies of rotator cuff integrity have shown that single row
arthroscopic repairs had a greater rate of structural failure than open rotator cuff repairs
(Galatz, et al., 2004; Liu & Baker, 1994; Thomazeau, et al., 1997). Gerber, et al. (1994,
p. 378) stated “the ideal repair should have high initial fixation strength, allow minimal
gap formation, and maintain mechanical stability until solid healing; it is clear that weak
initial fixation leads to gap formation under load, poor healing and possible complete
failure”.
27
A study conducted by Apreleva and colleagues (2002) evaluated the three-dimensional
rotator cuff footprint in the normal rotator cuff and after several methods of arthroscopic
supraspinatus tendon repair. They determined that 67% of the original rotator cuff
footprint was restored using a single row of suture anchors, while the double-row suture
repairs restored up to 85% of the surface area. The results showed that the rotator cuff
footprint is a complex three-dimensional structure, covering a large surface of the
humerus, that cannot be restored with a simple single row of sutures (Apreleva, et al.,
2002). Similarly, Kim, et al. (2006) found that the use of a double-row suture technique
created a more superior suture construct, with greater strength and stiffness, resulting in
less gap formation and less strain over the rotator cuff footprint, compared with a single-
row repair. By providing a double row of fixation, the number of fixation points doubles
compared with a single-row repair, potentially improving mechanical strength and
function by providing more complete healing across the rotator cuff footprint (Lo &
Burkhart, 2003).
Despite the many surgical repair techniques, there remains concern regarding the ability
of the rotator cuff insertion to fully heal following the repair (Castricini, et al., 2010;
Gulotta & Rodeo, 2009; Kovacevic & Rodeo, 2008), with recurrent tearing occurring
frequently (Cheung, et al., 2010). Re-tears have been reported to occur in 11-94% of
rotator cuff repair surgeries – dependent upon the size of the tear, the level of tendon
degeneration, and fatty infiltration present at the time of surgery, type of suture anchors
and suture method used during surgery, compliance with post-operative rehabilitation
guidelines and patient age (Boileau, et al., 2005; Cheung, et al., 2010; Cho & Rhee, 2009;
Galatz, et al., 2004; Gulotta & Rodeo, 2009; Sugaya, et al., 2007). The authors that
published these re-tear rates reported the predictors of re-tear included: larger tear size,
28
greater levels of tendon degeneration and fatty infiltration, and increased age at the time
of surgery, as well as non-compliance with the post-operative rehabilitation guidelines.
The large range in re-tear rates is likely due to differences in research methodology and
study follow up timeframes.
There are a variety of re-tear rates reported in the literature, with comparisons between
the open, mini-open and arthroscopic surgical approaches. Re-tear rates have been
reported as high as 80-90% in the radiology literature, and as high as 57% in orthopaedic
literature (Barber, et al., 2011; Charousset, et al., 2010; Liem, Bartl, et al., 2007; Liem,
Lichtenberg, et al., 2007).
A study conducted by Kluger, et al. (2011) reported the overall failure rate of patients
having mini-open rotator cuff repair surgery was 33% (n=107, average age=59.5 ± 9.2
years). Furthermore, they reported that 74% of the failures occurred atraumatically in the
first 3 months, 11% occurred between 3-6 months following surgery, and the remaining
failures occurred 2 to 5 years post surgery, and were related to sporting activities or direct
trauma. Miller, et al. (2011) reported 41% of their arthroscopically repaired rotator cuffs
had re-torn (n=22); with seven of the nine (78%) re-tears occurring within the first 3
months after surgery. Another study found that 100% of re-tears occurred in the first 3
months post surgery (Nho, et al., 2009).
DeFranco, et al. (2007) reported a 40% re-tear rate (n=30, average age=56.3 ±12.3 years)
in patients who underwent isolated supraspinatus repair arthroscopically, using a single-
row suture technique. They noted that patients in the no-tear group were significantly
younger than those in the re-tear group (51 ± 12 vs 64 ± 9 years, p<0.01).
29
Oh, et al. (2010) reported similar results; patients with an intact repair were significantly
younger than the failed repair group (58.4 ± 8.7 years vs 63.7 ± 7.5 years). Similarly,
Boileau, et al. (2005) reported that only 43% of the patients over the age of 65 years had
completely healed tendons (p=0.001). In this study, the rotator cuff was completely
healed in 71% of the patients, 62 of the 65 patients reported they were satisfied with the
result, and those with intact repairs had significantly greater shoulder strength.
Charousset, et al. (2010) showed that patients older than 65 (mean age 70 years, range =
65-85 years) who underwent an arthroscopic rotator cuff surgery at 6 months post-surgery
had a re-tear rate of 42%. Furthermore, the isolated supraspinatus tears showed superior
healing (28.9% failure rate), however those that had a massive tear (supraspinatus
retracted to the glenoid) had 100% failure rate. This indicated that arthroscopic tendon
repair can be considered a successful procedure for the older patient with a small or
medium tear, particularly where the tear is isolated to the supraspinatus tendon
(Charousset, et al., 2010).
There has been much debate about whether the integrity of repair of the rotator cuff
tendon affects functional outcome, with the trend being towards a better outcome with an
intact repair (DeFranco, et al., 2007; Galatz, et al., 2004; Lafosse, et al., 2007; Liem,
Bartl, et al., 2007; Oh, et al., 2010). While the radiographs may show failures at the repair
site, often the patient may still have pain relief; however, studies have shown they have
inferior function results when compared to patients with healed repairs (Boileau, et al.,
2005; Galatz, et al., 2004; Gulotta & Rodeo, 2009; Lafosse, et al., 2007). Lam and Mok
(2004), and Verma, et al. (2010) reported in older patients treated for rotator cuff repair
(open and arthrosopic respectively), that over 90% had reduced pain post-surgery. They
did not, however, consider the structural integrity of the repair sites.
30
ATTEMPTS TO REDUCE HIGH ROTATOR CUFF TENDON RE-TEAR
RATES
Though surgery is successful for many patients, the quality and speed of post-operative
healing remains problematic, with a number of studies demonstrating that native tendon-
to-bone insertions were not restored after tendon repair surgery (Carpenter, et al., 1998;
Kovacevic & Rodeo, 2008; Rodeo, et al., 2007). Tendons comprise specialised cells
including tenocytes and water (Cheung, et al., 2010; Molloy, et al., 2003; Sampson, et al.,
2008), as well as type I collagen fibres which orient towards a continuous insertion point
on the humerus (Clark & Harryman, 1992; Sampson, et al., 2008). The vasculature is
organised and dispersed through the tendon, however, the vessels decrease in number and
size closer to the bone (Cheung, et al., 2010; Clark & Harryman, 1992). There are four
distinct zones of tissue running longitudinally; tendon, non-mineralised fibrocartilage,
mineralised fibrocartilage and bone (Carpenter, et al., 1998; Clark & Harryman, 1992).
Tendons are required to transfer great forces and, as a result, can be susceptible to injury
when overloaded (Sampson, et al., 2008). With continuous overuse, micro tears can form
in the collagen fibres, which may lead to tendinosis or tendinopathy (Millett, et al., 2006;
Mishra, et al., 2009; Sampson, et al., 2008). When this occurs, the injured tendon heals
by scarring, and with its inferior biomechanical properties, affects function and increases
the risk of re-injury (Carpenter, et al., 1998; Sampson, et al., 2008). Tendons tend to heal
at a slower rate compared with other connective tissues, due to poor vascularisation
(Castricini, et al., 2010; Jo, et al., 2011; Sampson, et al., 2008).
General healing follows a pathway, beginning with inflammation, continuing with
cellular and matrix proliferation, followed by tissue formation and maturation, and finally
31
tissue remodelling (Lopez-Vidriero, et al., 2010); this can also be applied to tendon
healing. Tendon-to-bone healing is divided into three stages: the inflammatory stage, the
repair stage and the remodelling stage (Carpenter, et al., 1998; Cheung, et al., 2010;
Gulotta & Rodeo, 2009; Mishra, et al., 2009; Molloy, et al., 2003). Following a tendon
injury or surgical repair, the final bone-to-tendon insertion point bears little resemblance
to the original insertion (Kovacevic & Rodeo, 2008). The overall structure, composition
and organisation of the normal insertion site does not regenerate (Kovacevic & Rodeo,
2008). Instead of the four distinct zones following the remodelling stage of healing, the
tendon and bone become joined by a layer of fibrovascular scar tissue dominated by
poorly organised type III collagen fibres (Carpenter, et al., 1998; Cheung, et al., 2010).
Mechanically, this fibrous scar tissue is weaker than the native insertion site, and may
contribute to the high number of repair failures (Carpenter, et al., 1998; Cheung, et al.,
2010).
In an attempt to reduce the number of rotator cuff repair failures, researchers have focused
their attention on ways to minimise the scar tissue formation and at the same time,
promote the regeneration of the fibrocartilagenous insertion zones (Gulotta & Rodeo,
2009; Maniscalco, et al., 2008). Initially, studies looked at improving the biomechanical
strength of the repair site by using stronger sutures and double row repairs (Apreleva, et
al., 2002; Gulotta & Rodeo, 2009; Kim, et al., 2006; Lo & Burkhart, 2003), however,
even with these techniques, failed healing and/or re-tears still occurred in up to 12% of
cases (Lafosse, et al., 2007). Although improved biomechanics may slightly improve
tendon healing, it has been suggested that biologic augmentation of the healing process
may be required to further reduce the scar tissue formation at the repair site, and help
regenerate a normal fibrocartilagenous transition zone (Gulotta & Rodeo, 2009;
Maniscalco, et al., 2008), which may improve the strength of the repair.
32
Because of the problems faced with tendon healing following injury or surgical repair,
much of the research has been directed towards understanding the mechanisms of tendon
healing at the molecular level (Anitua, et al., 2005; Anitua, et al., 2007; Lyras, et al.,
2010; Molloy, et al., 2003; Randelli, et al., 2009). This research has been undertaken in
an effort to develop complimentary therapies to facilitate tendon healing via individual
and groups of molecules that are known to have beneficial roles in the healing process.
The more recent knowledge gained about tissue biology and the complexity of the
regulation of growth factors in normal tissue structure, as well as in reaction to tissue
damage, shows the important and effective role of an application of growth factors in the
healing of damaged tissue (Filardo, et al., 2010).
Growth factors have an essential role in the body’s healing process and tissue formation
(Anitua, et al., 2006). All stages of the repair process are controlled by a variety of
cytokines and growth factors that act as regulators of the majority of basic cell functions
(Anitua, et al., 2006). Growth factors influence many of the processes common to tissue
repair and disease, including angiogenesis, chemotaxis and cell proliferation, as well as
controlling the synthesis and degradation of extracellular matrix proteins (Anitua, et al.,
2006).
As mentioned earlier, tendon healing follows a pattern (inflammatory phase, repair phase
and remodelling phase). When tissue is damaged, blood vessels rupture which signals
the release of molecules to trigger coagulation to coordinate the formulation of a clot
around the affected area (Molloy, et al., 2003). The clot contains cells and platelets that
immediately release a variety of molecules (including growth factors), causing acute and
local inflammation (Molloy, et al., 2003). It is during the inflammatory phase that
33
extrinsic cells (neutrophils and macrophages) which are responsible for phagocytosis, and
intrinsic cells (endotenon and epitenon cells) produce another battery of cytokines which
initiates the repair phase (Molloy, et al., 2003). At this stage that we see the collagen
deposition and granular tissue formation, as well as neovascularisation, extrinsic
fibroblast migration and intrinsic fibroblast proliferation (Anitua, et al., 2005; Molloy, et
al., 2003).
Platelets are responsible for haemostasis and coagulation (Anitual, et al., 2004; Lopez-
Vidriero, et al., 2010), and also contain alpha granules with various molecules (growth
factors, endostatins, antipoietins and thrombospondin) that are secreted upon activation
during the healing process (Anitua, et al., 2004; Lopez-Vidriero, et al., 2010), assisting in
the construction of new connective tissue and revascularisation, making up approximately
6% of a blood specimen (Sampson, et al., 2008).
34
Growth factors important in tendon healing/regeneration
Growth factors have a number of crucial roles in tendon healing. Numerous studies have
revealed the complexity of the regulation of growth factors in response to tissue damage
and the important role they play in tendon healing (Anitua, et al., 2005; Anitua, et al.,
2007; Lyras, et al., 2010; Molloy, et al., 2003; Randelli, et al., 2009; Rodeo, et al., 2007).
Factors secreted from platelets such as transforming growth factor-ß (TGF- ß), platelet-
derived growth factor (PDGF), vascular endothelial growth factors (VEGF), basic
fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) are markedly up-
regulated throughout the tendon repair process (Anitua, et al., 2005; Molloy, et al., 2003;
Randelli, et al., 2009). They can be potentially produced by both intrinsic and extrinsic
cells, often have dose-dependent effects, require specific receptors to be active, and
usually work in synergy with other signalling molecules (Molloy, et al., 2003). Growth
factors are one of the largest groups of molecules involved in the healing process of
tendons and ligaments (Molloy, et al., 2003), with an outline provided below of some of
their functions and behaviours.
TGF- ß is active in almost all stages of tendon healing, having varied effects such as
stimulating extrinsic cell migration, regulating proteinases, fibronectin binding
interactions, termination of cell proliferation via cyclin-dependent kinase inhibitors and
stimulation of collagen production (Anitua, et al., 2005; Molloy, et al., 2003; Randelli, et
al., 2009). TGIF-ß levels have been shown to dramatically increase following tendon
injury, and it is believed to play an important role in the initial inflammatory response to
tissue damage (Molloy, et al., 2003).
35
PDGF is secreted by platelets during the early phases of inflammation and has been
identified at fracture sites (Randelli, et al., 2009). It is thought that PGDF may play a
significant role in the early stages of healing by inducing the synthesis of other growth
factors, such as IGF-1 (Molloy, et al., 2003; Randelli, et al., 2009). The role of PDGF in
tendon repairs appears to be most relevant in the remodelling phase where it has been
observed to stimulate collagen and non-collagen protein production, and DNA synthesis,
in a dose-dependent manner.
VEGF has a small role in early cellular migration and proliferation, however, has been
found to be most active after the inflammation phase during the proliferation and
remodelling phases, where it is a powerful stimulator of angiogenesis (Anitua, et al.,
2005; Molloy, et al., 2003). Increased levels of VEGF at the site of injury correlate with
a well-defined pattern of vascular ingrowth from the epi- and intra-tendinous blood
supply towards the site of repair. This increased vascularisation proceeds along the
epitenon, through a normally avascular area, providing extrinsic cells, nutrients and
growth factors to the injured site.
The bFGF promotes growth and differentiation in a range of cells, including epithelial
cells, myocytes, osteoblasts and chondocytes (Molloy, et al., 2003; Randelli, et al., 2009).
In tendons it has been shown to be a potent stimulator of angiogenesis, cellular migration
and proliferation. Kobayashi and colleagues (1997) found that bDGF provided a boost
to the initial stages of healing, and that all the subsequent steps proceeded with
significantly greater speed and efficiency.
IGF-1 is an important mediator in all phases of wound healing, particularly in the
inflammatory and proliferative phases (Molloy, et al., 2003). It is a versatile signal
36
molecule, having numerous and varied activities during tendon healing, especially when
working in synchrony with other growth factors (Molloy, et al., 2003). Its primary role
is to stimulate the proliferation and migration of fibroblasts and other cells at the repair
site, and subsequently increase the production of collagens and other extracellular matrix
structures during the remodelling phase (Anitua, et al., 2005; Molloy, et al., 2003).
It has been suggested that the concentrated addition of the above mentioned growth
factors might improve tissue healing. Recently a technique has been developed to extract
useable growth factors from autologous blood, which can be injected around an injury or
repair site, called platelet rich plasma (PRP).
Platelet rich plasma
Platelets contribute to haemostasis by preventing blood loss at sites of vascular injury,
and contain large numbers of cytokines and growth factors that play a key role in bone
regeneration and soft tissue maturation (Anitua, et al., 2006). PRP has emerged as a new
technology believed to stimulate the revascularisation of soft tissue and increase the
concentration of growth factors to improve and accelerate wound, bone, muscle and
tendon healing (Barber, et al., 2011; Peerbooms, et al., 2010). It is an autologous
concentration of platelets in a small volume of plasma, which, once activated, undergoes
degranulation to release growth factors with healing properties (Kajikawa, et al., 2008;
Lopez-Vidriero, et al., 2010). Because the PRP preparation is obtained from the patient’s
own blood, concerns regarding immunogenic reactions and disease transmission are
eliminated (Anitua, et al., 2006). Important growth factors identified in PRP include
TGF- ß, PDGF, VEGF, bFGF and IGF-1 (Lyras et al., 2010). As well as containing
platelets and concentrated growth factors, PRP also consists of plasma with fibrin, which
37
acts as a scaffold for primary cell migration and differentiation, functioning as a
biological glue (Anitua, et al., 2006; Lopez-Vidriero, et al., 2010).
The concept of using growth factors to assist healing dates back to the early 1980’s, where
it was first used to assist in wound healing (Knighton, et al., 1982). Initially it was thought
that platelets acted exclusively during clotting; however it has since been discovered that
platelets also release many bioactive proteins responsible for attracting microphages,
mesenchymal stem cells and osteoblasts, which promote the removal of necrotic tissue,
as well as enhancing tissue regeneration and healing (Sampson, et al., 2008). The early
use of PRP in the 1990’s was as a biological glue (Gibble & Ness, 1990). Because of the
high proportions of fibrin, these “glues” were used primarily in maxillofacial surgery
(Lopez-Vidriero, et al., 2010). It was during this time that PRP preparations were
discovered to have bone-forming properties, as well as anti-inflammatory and
antibacterial qualities, attributed mainly to the high concentration of platelets (Lopez-
Vidriero, et al., 2010).
Since then, research has been conducted using PRP in a variety of tissues to accelerate
and assist the healing process. Such areas include cosmetic surgery and wound healing
(Eppely, et al., 2004), as well as most orthopaedic disciplines, such as chronic patella
tendon injuries (Filardo, et al., 2010) and defects (Lyras, et al., 2010), lateral epicondylitis
(Mishra & Pavelko, 2006; Peerbooms et al., 2010), Achilles tendon injuries (Aspenberg
& Virchenko, 2004; Sanchez, et al., 2007), bone allograft integration, rotator cuff tendon
tears (Maniscalco, et al., 2008) and rotator cuff tendon repair surgery (Barber, et al., 2011;
Castricini, et al., 2010; Kovacevic, et al., 2008; Randelli, et al., 2008; Randelli, et al.,
2011).
38
Lopez-Vidriero and colleagues (2010) described the characteristics of the main PRP
commercial products currently available on the market. The term “PRP” has been
controversial in the literature, because this generic terminology doesn’t differentiate
between the various commercial products available, and their respective protocols
(Lopez-Vidriero, et al., 2010; Sanchez, et al., 2010). Concerns have been raised because
different products show varying biologic effects (Anitua, et al., 2009). The main
differences between commercial PRP systems are: speed and number of centrifugations
that lead to different platelet concentrations, the use of anticoagulant, the presence of
leukocytes in the preparation and the use of an activator (Anitua, et al., 2009; Lopez-
Vidriero, et al., 2010). The actual platelet concentration required to have a clinically
significant effect has not yet been determined, and a higher concentration may not
necessarily be superior (Barber, et al., 2011). It is important that these factors be taken
into account when analysing published results, and when surgeons are deciding on which
system to use (Anitua, et al., 2006; Castillo, et al., 2011; Lopez-Vidriero, et al., 2010).
Platelet-rich plasma and tendon injury
Aspenberg and Virchenko (2004) investigated the use of PRP to augment rat Achilles
tendon tears, finding greater maturation in tendon callus, but also reported increased force
to failure and ultimate stress in PRP treated animals (Virchenko & Aspenberg, 2006).
PRP was found by Kajikawa, et al. (2008) to enhance mobilisation of circulation-derived
cells to the injection area, and that PRP induced type I collagen production and increased
the proliferation of microphages at three and seven days.
Mishra and Pavelko (2006) reported on the use of PRP in patients with chronic severe
elbow tendinitis, who had failed a standardised, non-operative treatment protocol. They
39
found a 60% improvement in pain scores for those patients treated with PRP, compared
with a 16% improvement in the control group at 8 weeks following treatment. At final
follow-up, the PRP recipients reported over 90% reduction in pain compared to their pre-
treatment scores, and 93% of PRP patients were fully satisfied with this treatment. It
should be noted however, that this was a small sample, non-randomised study.
Anitua and colleagues (2007) reported faster recovery in athletes who underwent PRP-
enhanced Achilles tendon repair, compared to a retrospective control group of athletes
who had surgery alone. Those treated with PRP recovered their range of motion earlier,
had no wound complications and returned to training activities earlier than the control
patients.
Platelet-rich plasma preparations and rotator cuff tendon repair
Review of the literature reveals substantial rates of failure in the surgical treatment of
smaller tears. A number of studies have looked into the use of PRP constructs to
potentially enhance rotator cuff healing (Barber, et al., 2011; Castricini, et al., 2010;
Gumina, et al., 2012; Randelli, et al., 2008; Randelli, et al., 2011), but currently there are
no clear guidelines or agreement on the safest or most effective augmentation. A pilot
study conducted by Randelli and colleagues (2008) demonstrated the application of PRP
during arthroscopic rotator cuff repair is safe and effective, and results remained stable
with time.
Castricini, et al. (2010) suggest that the use of autologous platelet-rich fibrin matrix
(PRFM) for augmentation of a repair of a small or medium rotator cuff tear does not
improve shoulder function or cuff integrity, when compared to a control group at 16
40
months post-surgery. They suggested that, given the variety of PRP products on the
market, there might be another preparation that could be more effective. Barber and
colleagues (2011) also used a PRP fibrin matrix (Cascade, by Musculoskeletal Transplant
Foundation, NJ), which did not have thrombin activation, nor contain leukocytes, opting
to suture two lots of the construct into the repair. While there was no statistical difference
between the PRP and control groups in terms of functional outcomes, the MRI results
indicated that the PRP group had significantly lower re-tear rates (P= 0.03), with MRI
follow-up at 4 months post surgery.
A study by Gumina, et al. (2012) compared clinical and MRI results of arthroscopic
rotator cuff repair with and without the use of platelet-leukocyte membrane (n=80),
stating that the use of the membrane was associated with significantly better repair
integrity (p=0.04). However, this improvement in integrity was not associated with
greater improvement in functional outcomes.
Randelli, et al. (2011) published long-term results from the use of an intra-operative
application of PRP in combination with a rotator cuff repair of small to massive tears
(n=53; treatment group n=26, control group n=27) completed by a single surgeon. Pain
scores in the treatment group were significantly lower than the control group at 3, 7, 14
and 30 days post surgery (p<0.05). Functional scores (Simple Shoulder Test (SST),
University of California (UCLA and Constant) and strength in external rotation were
significantly higher in the treatment group at 3 months post surgery; however, there was
no significant difference between the groups after 6, 12 and 24 months. The 12-month
MRI analysis showed no difference in the rotator cuff healing rate between the two
groups. They concluded that the PRP application reduced pain in the first post-operative
months, and that smaller tears with less retraction would benefit from PRP.
41
More recently, Werthel and colleagues (2014) reported long term results (mean 19 month
follow-up ± 4.2) on the use of an intra-operative injection of PRP during surgical rotator
cuff repair of full thickness symptomatic supraspinatus tendon tear (retraction less than 3
in the Patte classification). No significant differences were noted functionally or
structurally between the treatment and control groups, except for a lower VAS for pain
score at final follow-up (p < 0.001). There were some limitations of this study; subjects
were not randomised, and a different surgeon operated on the subjects in each group.
There was also a significant age difference between the treatment and control groups, and
the authors suggest this may have contributed to the difference in pain reported at final
follow-up.
SUMMARY
Significant re-tear rates reported in the literature despite advancements in surgical and
suture anchor technique, along with the lengthy tendon healing timeline, has established
the need to investigate biological therapies that may improve and/or accelerate tendon
healing. Biological augmentation in conjunction with rotator cuff repair has the potential
to improve tendon healing. While research in this area has shown it to be safe, results
remain inconclusive, and have not been demonstrated sufficiently to warrant regular
clinical use.
While it has been well established that the longer-term structural and functional results
(>12 months follow-up) have not differed significantly, little research has centred on the
early tendon healing. In a primate model, Sonnabend, et al. (2010) showed that a
significant proportion of Sharpey fibres begin to reconstitute at 3 months, with maturation
42
at 4 months following surgery. It has also been well documented that the majority of re-
tears occur within the first 3 months of surgery (Kluger, et al., 2011; Miller, et al. 2011;
Nho, et al., 2009), suggesting that the early tendon healing stage is critical for long term
success.
There are a number of variables that may affect the efficacy of PRP in combination with
rotator cuff repair, including tendon tear size, formulation of PRP used and timing of
delivery; with all previous studies to our knowledge using time zero delivery at the time
of surgery. We propose that the delayed and repeated injection of PRP (Arthrex) at 7 and
14 days post-surgery will give the best opportunity to enhance early tendon healing and
functional recovery following rotator cuff repair.
REFERENCES
Ainsworth, R., & Lewis, J. (2007). Exercise therapy for the conservative management of
full thickness tears of the rotator cuff: a systematic review. Br J Sports Med, 41,
200-210.
Anitua, E., Andia, I., Ardanza, B., Nurden, P., & Nurden, A. T. (2004). Autologous
platelets as a source of proteins for healing and tissue regeneration. Thromb
Haemost, 91(1), 4-15.
Anitua, E., Andia, I., Shanchez, M., Azofra, J., del Mar Zalduendo, M., de la Fuente, M.,
et al. (2005). Autologous preparation rich in growth factors promote proliferation
and induce VEGF and HGF production by human tendon cells in culture. Journal
of Orthopaedic Research, 23(2), 281-286.
43
Anitua, E., Sanchez, M., Nurden, A. T., Nurden, P., Orive, G., & Andia, I. (2006). New
insights into and novel applications for platelet-rich fibrin therapies. Trends
Biotechnol, 24(5), 227-234.
Anitua, E., Sanchez, M., Nurden, A. T., Zalduendo, M., de la Fuente, M., Azofra, J.,
(2007). Reciprocal actions of platelet-secreted TGF-beta1 on the production of
VEGF and HGF by human tendon cells. Plast Reconstr Surg, 119(3), 950-959.
Anitua, E., Sanchez, M., Orive, G., & Andia, I. (2009). Shedding light in the controversial
terminology for platelet rich products. J Biomed Mater Res A, 90(4), 1262-1263.
Apreleva, M., Ozbaydar, M., Fitzgibbons, P. G., & Warner, J. J. (2002). Rotator cuff
tears: the effect of the reconstruction method on three-dimensional repair site area.
Arthroscopy, 18(5), 519-526.
Ardic, F., Kahraman, Y., Kacar, M., Kahraman, M. C., Findikoglu, G., & Yorgancioglu,
Z. R. (2006). Shoulder impingement syndrome: relationships between clinical,
functional, and radiologic findings. Am J Phys Med Rehabil, 85(1), 53-60.
Aspenberg, P., & Virchenko, O. (2004). Platelet concentrate injection improves Achilles
tendon repair in rats. Acta Orthop Scand, 75(1), 93-99.
Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing
influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the
Journal of Arthroscopic and Related Surgery, 27(8), 1029-1035.
Bartolozzi, A., Andreychik, D., & Ahmad, S. (1994). Determinants of outcome in the
treatment of rotator cuff disease. Clin Orthop Relat Res, (308), 90-97.
Baydar, M., Akalin, E., El, O., Gulbahar, S., Bircan, C., Akgul, O., et al. (2009). The
efficacy of conservative treatment in patients with full-thickness rotator cuff tears.
Rheumatol Int, 29(6), 623-628.
44
Beaudreuil, J., Nizard, R., Thomas, T., Peyre, M., Liotard, J. P., Boileau, P., et al. (2009).
Contribution of clinical tests to the diagnosis of rotator cuff disease: a systematic
literature review. Joint Bone Spine, 76(1), 15-19.
Bennell, K., Coburn, S., Wee, E., Green, S., Harris, A., Forbes, A., et al. (2007). Efficacy
and cost-effectiveness of a physiotherapy program for chronic rotator cuff
pathology: a protocol for a randomised, double-blind, placebo-controlled trial.
BMC Musculoskelet Disord, 8, 86.
Bennett, W. F. (2003a). Arthroscopic repair of full-thickness supraspinatus tears (small-
to-medium): A prospective study with 2- to 4-year follow-up. Arthroscopy, 19(3),
249-256.
Bennett, W. F. (2003b). Arthroscopic repair of massive rotator cuff tears: a prospective
cohort with 2- to 4-year follow-up. Arthroscopy, 19(4), 380-390.
Bhatia, M., Singh, B., Nicolaou, N., & Ravikumar, K. J. (2009). Correlation between
rotator cuff tears and repeated subacromial steroid injections: a case-controlled
study. Ann R Coll Surg Engl, 91(5), 414-416.
Bigliani, L. U., Cordasco, F. A., McLlveen, S. J., & Musso, E. S. (1992). Operative repair
of massive rotator cuff tears: Long-term results. J Shoulder Elbow Surg, 1(3), 120-
130.
Boileau, P., Brassart, N., Watkinson, D. J., Carles, M., Hatzidakis, A. M., & Krishnan, S.
G. (2005). Arthroscopic repair of full-thickness tears of the supraspinatus: does
the tendon really heal? . Journal of Bone and Joint Surgery (Am), 87(6), 1229-
1240.
Boissonault, W. G., Badake, M. B., Wooden, M. J., Ekedahl, S., & Fly, K. (2007). Patient
outcome following rehabilitation for rotator cuff repair surgery: the impact of
selected medical comorbidities. Journal of orthopaedic and sports physical
therapy, 37(6), 312-319.
45
Bokor, D. J., Hawkins, R. J., Huckell, G. H., Angelo, R. L., & Schickendantz, M. S.
(1993). Results of nonoperative management of full-thickness tears of the rotator
cuff. Clin Orthop Relat Res, (294), 103-110.
Brandt, T. D., Cardone, B. W., Grant, T. H., Post, M., & Weiss, C. A. (1989). Rotator
cuff sonography: a reassessment. Radiology, 173(2), 323-327.
Brox, J. I., Gjengedal, E., Uppheim, G., Bohmer, A., Brevik, J. I., Ljunggren, A. E., et al.
(1999). Arthroscopic surgery versus supervised exercises in patients with rotator
cuff disease (stage II impingement syndrome): a prospective, randomised,
controlled study in 125 patients with 2 1/2-year follow-up. Journal of shoulder
and elbow surgery, 8(2), 102-111.
Carpenter, J. E., Thomopoulos, S., Flanagan, C. L., De Bano, C. M., & Soslowsky, L. J.
(1998). Rotator cuff defect healing: a biomechanic and histologic analysis in an
animal model. . Journal of Shoulder and Elbow Surgery, 7(6), 599-605.
Castillo, T. N., Pouliot, M. A., Kim, H. J., & Dragoo, J. L. (2011). Comparison of growth
factor and platelet concentration from commercial platelet-rich plasma separation
systems. Am J Sports Med, 39(2), 266-271.
Castricini, R., Longo, U. G., De Benedetto, M., Panfoli, N., Pirani, P., Zini, R., et al.
(2010). Platelet-rich augmentation for arthroscopic rotator cuff repair: a
randomised control trial. Am J Sports Med, 39(2), 258-265.
Charousset, C., Bellaiche, L., Kalra, K., & Petrover, D. (2010). Arthroscopic repair of
full-thickness rotator cuff tears: is there tendon healing in patients aged 65 years
or older? Arthroscopy, 26(3), 302-309.
Cheung, E. V., Silverio, L., & Sperling, J. W. (2010). strategies of biologic augmentation
of rotator cuff repair: a review. Clin orthop relat res, 468(6), 1476-1884.
46
Cho, N. S., & Rhee, Y. G. (2009). The factors affecting the clinical outcome and integrity
of arthroscopically repaired rotator cuff tears of the shoulder. Clin Orthop Surg,
1(2), 96-104.
Clark, J. M., & Harryman, D. T. (1992). Tendons, ligaments and capsule of the rotator
cuff. Gross and microscopic anatomy. Journal of Bone and Joint Surgery (Am),
74(5), 713-725.
Codsi, M. J., Rodeo, S. A., Scalise, J. J., Moorehead, T. M., & Ma, C. B. (2014).
Assessment of rotator cuff repair integrity using ultrasound and magnetic
resonance imaging in a multicenter study. J Shoulder Elbow Surg, 23(10), 1468-
1472.
Cofield, R. H. (1985). Rotator cuff disease of the shoulder. J Bone Joint Surg Am, 67(6),
974-979.
Darlington, L. G., & Coomes, E. N. (1977). The effects of local steroid injection for
supraspinatus tears. Rheumatol Rehabil, 16(3), 172-179.
DeFranco, M. J., Bershadsky, B., Ciccone, J., Yum, J. K., & Iannotti, J. P. (2007).
Functional outcome of arthroscopic rotator cuff repairs: a correlation of anatomic
and clinical results. Journal of shoulder and elbow surgery, 16(6), 759-765.
Del Buono, A., Battery, L., Denaro, V., Maccauro, G., & Maffulli, N. (2011).
Tendinopathy and inflammation: some truths. Int J Immunopathol Pharmacol,
24(1 Suppl 2), 45-50.
Downie, B. K., & Miller, B. S. (2012). Treatment of rotator cuff tears in older individuals:
a systematic review. J Shoulder Elbow Surg, 21(9), 1255-1261.
Ekeberg, O. M., Bautz-Holter, E., Tveita, E. K., Juel, N. G., Kvalheim, S., & Brox, J. I.
(2009). Subacromial ultrasound guided or systemic steroid injection for rotator
cuff disease: randomised double blind study. BMJ, 338, a3112.
47
Eppely, B. L., Woodell, J. E., & Higgins, J. (2004). Platelet quantification and growth
factor analysis from platelet-rich plasma: implications for wound healing. Plastic
and Reconstructive Surgery, 114(6), 1502-1508.
Fehringer, E. V., Sun, J., VanOeveren, L. S., Keller, B. K., & Matsen, F. A. (2008). Full-
thickness rotator cuff tear prevalence and correlation with function and co-
morbidities in patients sixty-five years and older. Journal of Shoulder and Elbow
Surgery, 17(6), 881-885.
Filardo, G., Kon, E., Della Villa, S., Vincentelli, F., Fornasari, P. M., & Marcacci, M.
(2010). Use of platelet-rich plasma for the treatment of refractory jumper's knee.
International Orthopaedics, 34, 909-915.
Galatz, L. M., Ball, C. M., Teefey, S. A., Middleton, W. D., & Yamaguchi, K. (2004).
The outcome and repair of completely arthroscopically repaired large and massive
rotator cuff tears. J Bone and Joint Surgery (Am), 86(2), 219-224.
Galatz, L. M., Griggs, S., Cameron, B. D., & Iannotti, J. P. (2001). Prospective
longitudinal analysis of postoperative shoulder function: a ten-year follow-up
study of full-thickness rotator cuff tears. J Bone Joint Surg Am, 83-A(7), 1052-
1056.
Gartsman, G. M. (2001). Arthroscopic rotator cuff repair. Clin Orthop Relat Res (390),
95-106.
Gerber, C., Schneeberger, A. G., Beck, M., & Schlegel, U. (1994). Mechanical strength
of repairs of the rotator cuff. J Bone Joint Surg Br, 76(3), 371-380.
Ghodadra, N. S., Provencher, M. T., Verma, N. N., Wilk, K. E., & Romeo, A. A. (2009).
Open, mini-open, and all-arthroscopic rotator cuff repair surgery: indications and
implications for rehabilitation. J Orthop Sports Phys Ther, 39(2), 81-89.
Gialanella, B., & Prometti, P. (2011). Effects of corticosteroids injection in rotator cuff
tears. Pain Med, 12(10), 1559-1565.
48
Gibble, J. W., & Ness, P. M. (1990). Fibrin glue: the perfect operative sealant?
Transfusion, 30(8), 741-747.
Gulotta, L. V., & Rodeo, S. A. (2009). Growth factors for rotator cuff repair. Clinical
Sports Medicine, 28, 13-23.
Gumina, S., Campagna, V., Ferrazza, G., Giannicola, G., Fratalocchi, F., Milani, A., et
al. (2012). Use of platelet-leukocyte membrane in arthroscopic repair of large
rotator cuff tears: a prospective randomized study. J Bone Joint Surg Am, 94(15),
1345-1352.
Haahr, J. P., Ostergaard, S., Dalsgaard, J., Norup, K., Frost, P., Lausen, S., et al. (2005).
Exercises versus arthroscopic decompression in patients with subacromial
impingement: a randomised, controlled study in 90 cases with a one year follow
up. Ann Rheum Dis, 64(5), 760-764.
Hay, E. M., Paterson, S. M., Lewis, M., Hosie, G., & Croft, P. (1999). Pragmatic
randomised controlled trial of local corticosteroid injection and naproxen for
treatment of lateral epicondylitis of elbow in primary care. BMJ, 319(7215), 964-
968.
Hughes, P. C., Taylor, N. F., & Green, R. A. (2008). Most clinical tests cannot accurately
diagnose rotator cuff pathology: a systematic review. Aust J Physiother, 54(3),
159-170.
Iannotti, J. P., Zlatkin, M. B., Esterhai, J. L., Kressel, H. Y., Dalinka, M. K., & Spindler,
K. P. (1991). Magnetic resonance imaging of the shoulder. Sensitivity, specificity,
and predictive value. J Bone Joint Surg Am, 73(1), 17-29.
Itoi, E., & Tabata, S. (1992). Conservative treatment of rotator cuff tears. Clin Orthop
Relat Res (275), 165-173.
49
Jo, C. H., Kim, J. E., Yoon, K. S., Lee, J. H., Kang, S. B., Han, H. S., et al. (2011). Does
platelet-rich plasma accelerate recovery after rotator cuff repair? A prospective
cohort study. Am J Sports Med, 39(10), 2082-2090.
Kajikawa, Y., Morihara, T., Sakamoto, H., Matsuda, K., Oshima, Y., Yoshida, A., et al.
(2008). Platelet-rich plasma enhances the initial mobilization of circulation-
derived cells for tendon healing. J Cell Physiol, 215(3), 837-845.
Kasten, P., Keil, C., Grieser, T., Raiss, P., Streich, N., & Loew, M. (2011). Prospective
randomised comparison of arthroscopic versus mini-open rotator cuff repair of the
supraspinatus tendon. Int Orthop, 35(11), 1663-1670.
Kim, D. H., Elattrache, N. S., Tibone, J. E., Jun, B. J., DeLaMora, S. N., Kvitne, R. S.,
(2006). Biomechanical comparison of a single-row versus double-row suture
anchor technique for rotator cuff repair. Am J Sports Med, 34(3), 407-414.
Kinsella, K., & Velkoff, V. A. (2001). An ageing world: 2001.
Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term
survivorship of rotator cuff repairs using ultrasound and magnetic resonance
imaging analysis. Am J Sports Med, 39(10), 2071-2081.
Kneeland, J. B., Carrera, G. F., Middleton, W. D., Campagna, N. F., Ryan, L. M.,
Jesmanowicz, A., et al. (1986). Rotator cuff tears: preliminary application of high-
resolution MR imaging with counter rotating current loop-gap resonators.
Radiology, 160(3), 695-699.
Knighton, D. R., Hunt, T. K., Thakral, K. K., & Goodson, W. H. (1982). Role of platelets
and fibrin in the healing sequence. An invivo study of angiogenesis and collagen
synthesis. Annals of Surgery, 196(4), 379-387.
Kobayashi, D., Kurosaka, M., Yoshiya, S., & Mizuno, K. (1997). Effect of basic
fibroblast growth factor on the healing of defects in the canine anterior cruciate
ligament. Knee Surg Sports Traumatol Arthrosc, 5(3), 189-194.
50
Koubaa, S., Ben Salah, F. Z., Lebib, S., Miri, I., Ghorbel, S., & Dziri, C. (2006).
[Conservative management of full-thickness rotator cuff tears. A prospective
study of 24 patients]. Ann Readapt Med Phys, 49(2), 62-67.
Kovacevic, D., & Rodeo, S. A. (2008). Biological augmentation of rotator cuff tendon
repair. Clin Orthop Relat Res, 466(3), 622-633.
Kuhn, J. E. (2009). Exercise in the treatment of rotator cuff impingement: A systematic
review and a synthesized evidence-based rehabilitation protocol. Journal of
Shoulder and Elbow Surgery, 18, 138-160.
Lafosse, L., Brozska, R., Toussaint, B., & Gobezie, R. (2007). The outcome and structural
integrity of arthroscopic rotator cuff repair with use of the double-row suture
anchor technique. . Journal of Bone and Joint Surgery (Am), 89(7), 1533-1541.
Lam, F., & Mok, D. (2004). Open repair of massive rotator cuff tears in patients aged
sixty-five years or over: is it worthwhile? J Shoulder Elbow Surg, 13(5), 517-521.
Lehman, C., Cuomo, F., Kummer, F. J., & Zuckerman, J. D. (1995). The incidence of full
thickness rotator cuff tears in a large cadaveric population. Bull Hosp Jt Dis,
54(1), 30-31.
Levy, H. J., Uribe, J. W., & Delaney, L. G. (1990). Arthroscopic assisted rotator cuff
repair: preliminary results. Arthroscopy, 6(1), 55-60.
Lewis, J. S. (2010). Rotator cuff tendinopathy: a model for the continuum of pathology
and related management. Br J Sports Med, 44, 918-923.
Liem, D., Bartl, C., Lichtenberg, S., Magosch, P., & Habermeyer, P. (2007). Clinical
outcome and tendon integrity of arthroscopic versus mini-open supraspinatus
tendon repair: a magnetic resonance imaging-controlled matched-pair analysis.
Arthroscopy, 23(5), 514-521.
51
Liem, D., Lichtenberg, S., Magosch, P., & Habermeyer, P. (2007). Magnetic resonance
imaging of arthroscopic supraspinatus tendon repair. J Bone Joint Surg Am, 89(8),
1770-1776.
Liu, S. H., & Baker, C. L. (1994). Arthroscopically assisted rotator cuff repair: correlation
of functional results with integrity of the cuff. Arthroscopy, 10(1), 54-60.
Lo, I. K., & Burkhart, S. S. (2003). Double-row arthroscopic rotator cuff repair: re-
establishing the footprint of the rotator cuff. Arthroscopy, 19(9), 1035-1042.
Lopez-Vidriero, E., Goulding, K. A., Simon, D. A., Sanchez, M., & Johnson, D. H.
(2010). The use of platelet-rich plasma in arthroscopy and sports medicine:
optimizing the healing environment. Arthroscopy: the Journal of Arthroscopic
and Related Surgery, 26(2), 269-278.
Lyras, D., Kazakos, K., Verettas, D., Polychronidis, A., Simopoulos, C., Botaitis, S., et
al. (2010). Immunohistochemical study of angiogenesis after local administration
of platelet-rich plasma in a patellar tendon defect. Int Orthop, 34(1), 143-148.
MacDermid, J. C., Ramos, J., Drosdowech, D., Faber, K., & Patterson, S. (2004). The
impact of rotator cuff pathology on isometric and isokinetic strength, function,
and quality of life. J Shoulder Elbow Surg, 13(6), 593-598.
Maniscalco, P., Gambera, D., Lunati, A., Vox, G., Fossombroni, V., Beretta, R., et al.
(2008). The "cascade" membrane: a new PRP device for tendon ruptures.
Description and case report on rotator cuff tendon. Acta Biomed, 79, 223-226.
Milano, G., Grasso, A., Zarelli, D., Deriu, L., Cillo, M., & Fabbriciani, C. (2008).
Comparison between single-row and double-row rotator cuff repair: a
biomechanical study. Knee Surg Sports Traumatol Arthrosc, 16(1), 75-80.
52
Miller, B. S., Downie, B. K., Kohen, R. B., Kijek, T., Lesniak, B., Jacobson, J. A., et al.
(2011). When do rotator cuff repairs fail? Serial ultrasound examination after
arthroscopic repair of large and massive rotator cuff tears. Am J Sports Med,
39(10), 2064-2070.
Millett, P. J., Wilcox, R. B., O'Holleran, J. D., & Warner, J. J. P. (2006). Rehabilitation
of the rotator cuff: an evidence-based approach. J Am Acad Orthop Surg, 14(11),
599-609.
Mishra, Woodell, J. E., & Viera, A. (2009). Treatment of tendon and muscle using
platelet-rich plasma. Clin Sports Med, 28, 113-125.
Mishra, A., & Pavelko, T. (2006). Treatment of chronic elbow tendonosis with buffered
platelet-rich plasma. Am J Sports Med, 34(11), 1174-1178.
Mitchell, C., Adebajo, A., Hay, E., & Carr, A. (2005). Shoulder pain: diagnosis and
management in primary care. BMJ, 331(7525), 1124-1128.
Molloy, T., Wang, Y., & Murrell, G. A. C. (2003). The roles of growth factors in tendon
and ligament healing. Sports Medicine, 33(5), 381-394.
Murrell, G. A., & Walton, J. R. (2001). Diagnosis of rotator cuff tears. Lancet, 357(9258),
769-770.
Naqvi, G. A., Jadaan, M., & Harrington, P. (2009). Accuracy of ultrasonography and
magnetic resonance imaging for detection of full thickness rotator cuff tears. Int
J Shoulder Surg, 3(4), 94-97.
Neustadt, D. H. (1991). Local corticosteroid injection therapy in soft tissue rheumatic
conditions of the hand and wrist. Arthritis Rheum, 34(7), 923-926.
Nho, S. J., Shindle, M. K., Adler, R. S., Warren, R. F., Altchek, D. W., & MacGillivray,
J. D. (2009). Prospective analysis of arthroscopic rotator cuff repair: subgroup
analysis. J Shoulder Elbow Surg, 18(5), 697-704.
53
Nho, S. J., Shindle, M. K., Sherman, S. L., Freedman, K. B., Lyman, S., & MacGillivray,
J. D. (2007). Systematic review of arthroscopic rotator cuff repair and mini-open
rotator cuff repair. J Bone Joint Surg Am, 89 Suppl 3, 127-136.
Nichols, A. W. (2005). Complications associated with the use of corticosteroids in the
treatment of athletic injuries. Clin J Sport Med, 15(5), 370-375.
Norberg, F. B., Field, L. D., & Savoie, F. H., 3rd. (2000). Repair of the rotator cuff. Mini-
open and arthroscopic repairs. Clin Sports Med, 19(1), 77-99.
Notarnicola, A., & Moretti, B. (2012). The biological effects of extracorporeal shock
wave therapy (eswt) on tendon tissue. Muscles Ligaments Tendons J, 2(1), 33-37.
Oh, J. H., Kim, S. H., Kang, J. Y., Oh, C. H., & Gong, H. S. (2010). Effect of age on
functional and structural outcome after rotator cuff repair. Am J Sports Med,
38(4), 672-678.
Ostor, A. J., Richards, C. A., Prevost, A. T., Speed, C. A., & Hazleman, B. L. (2005).
Diagnosis and relation to general health of shoulder disorders presenting to
primary care. Rheumatology (Oxford), 44(6), 800-805.
Paavola, M., Kannus, P., Jarvinen, T. A., Jarvinen, T. L., Jozsa, L., & Jarvinen, M. (2002).
Treatment of tendon disorders. Is there a role for corticosteroid injection? Foot
Ankle Clin, 7(3), 501-513.
Paulos, L. E., & Kody, M. H. (1994). Arthroscopically enhanced "miniapproach" to
rotator cuff repair. Am J Sports Med, 22(1), 19-25.
Peerbooms, J. C., Sluimer, J., Bruijn, D. J., & Gosens, T. (2010). Positive effect of an
autologous platelet concetrate in lateral epicondylitis in a double-blind
randomised controlled trial: platelet-rich lasma versus corticosteroid
injectionwith a 1-year follow-up. The American Journal of Sports Medicine,
38(2), 255-262.
54
Randelli, P., Arrigoni, P., Ragone, V., Aliprandi, A., & Cabitza, P. (2011). Platelet rich
plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year
follow-up. J Shoulder Elbow Surg, 20(4), 518-528.
Randelli, P., Margheritini, F., Cabitza, P., Dogliotti, G., & Corsi, M. M. (2009). Release
of growth factors after arthroscopic acromioplasty. Knee Surg Sports Traumatol
Arthrosc, 17(1), 98-101.
Randelli, P. S., Arrigoni, P., Cabitza, P., Volpi, P., & Maffulli, N. (2008). Autologous
platelet rich plasma for arthroscopic rotator cuff repair. A pilot study. Disabil
Rehabil, 30(20-22), 1584-1589.
Reilly, P., Amis, A. A., Wallace, A. L., & Emery, R. J. (2003). Supraspinatus tears:
Propagation and strain alteration. Journal of Shoulder and Elbow Surgery, 12(2),
134-138.
Rodeo, S. A., Potter, H. G., Turner, A. S., Him, H. J., & Atkinson, B. L. (2007). Biologic
augmentation of rotator cuff tendon healing using a mixture of osteoinductive
growth factors: an experimental study. . Journal of Bone and Joint Surgery (Am),
87(6), 1229-1240.
Ruotolo, C., & Nottage, W. M. (2002). Surgical and non surgical treatment of rotator cuff
tears. Arthroscopy: the Journal of Arthroscopic and Related Surgery, 18(5), 527-
531.
Sampson, S., Gerhardt, M., & Mandelbaum, B. (2008). Platelet rich injetion grafts for
musculoskeletal injuries: a review. Curr Rev Musculoskelet Med, 1, 165-174.
Sanchez, M., Anitua, E., Azofra, J., Andia, I., Padilla, S., & Mujika, I. (2007).
Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin
matrices. Am J Sports Med, 35(2), 245-251.
55
Seibold, C. J., Mallisee, T. A., Erickson, S. J., Boynton, M. D., Raasch, W. G., & Timins,
M. E. (1999). Rotator cuff: evaluation with US and MR imaging. Radiographics,
19(3), 685-705.
Seitz, A. L., McClure, P. W., Finucane, S., Boardman, N. D., 3rd, & Michener, L. A.
(2011). Mechanisms of rotator cuff tendinopathy: intrinsic, extrinsic, or both?
Clin Biomech (Bristol, Avon), 26(1), 1-12.
Seltzer, S. E., Finberg, H. J., Weissman, B. N., Kido, D. K., & Collier, B. D. (1979).
Arthrosonography: gray-scale ultrasound evaluation of the shoulder. Radiology,
132(2), 467-468.
Sher, J.S., Uribe, J. W. Posada, A., Murphy, B. J. & Zlatkin, M. B. (1995). Abnormal
findings on magnetic resonance images of asymptomatic shoulder. Journal of
Bone and Joint Surgery Am, 77(1): 10-15.
Shibata, Y., Midorikawa, K., Emoto, G., & Naito, M. (2001). Clinical evaluation of
sodium hyaluronate for the treatment of patients with rotator cuff tear. J Shoulder
Elbow Surg, 10(3), 209-216.
Smidt, N., van der Windt, D. A., Assendelft, W. J., Deville, W. L., Korthals-de Bos, I.
B., & Bouter, L. M. (2002). Corticosteroid injections, physiotherapy, or a wait-
and-see policy for lateral epicondylitis: a randomised controlled trial. Lancet,
359(9307), 657-662.
Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-
594.
Sonnabend, D. H., Hughes, J. S., Giuffre, B. M., & Farrell, R. (1997). The clinical role
of shoulder ultrasound. Aust N Z J Surg, 67(9), 630-633.
Stannard, J. P., & Bucknell, A. L. (1993). Rupture of the triceps tendon associated with
steroid injections. Am J Sports Med, 21(3), 482-485.
56
Sugaya, H., Maeda, K., Matsuki, K., & Moriishi, J. (2007). Repair integrity and functional
outcome after arthroscopic double-row rotator cuff repair. A prospective outcome
study. J Bone Joint Surg Am, 89(5), 953-960.
Teefey, S. A., Rubin, D. A., Middleton, W. D., Hildebolt, C. F., Leibold, R. A., &
Yamaguchi, K. (2004). Detection and quantification of rotator cuff tears.
Comparison of ultrasonographic, magnetic resonance imaging, and arthroscopic
findings in seventy-one consecutive cases. J Bone Joint Surg Am, 86-A(4), 708-
716.
Tempelhof, S., Rupp, S., & Seil, R. (1999). Age-related prevalence of rotator cuff tears
in asymptomatic shoulders. Journal of Shoulder and Elbow Surgery, 8(4), 296-
299.
Thomazeau, H., Boukobza, E., Morcet, N., Chaperon, J., & Langlais, F. (1997).
Prediction of rotator cuff repair results by magnetic resonance imaging. Clin
Orthop Relat Res(344), 275-283.
Tillander, B., Franzen, L. E., Karlsson, M. H., & Norlin, R. (1999). Effect of steroid
injections on the rotator cuff: an experimental study in rats. J Shoulder Elbow
Surg, 8(3), 271-274.
Verhaar, J. A., Walenkamp, G. H., van Mameren, H., Kester, A. D., & van der Linden,
A. J. (1996). Local corticosteroid injection versus Cyriax-type physiotherapy for
tennis elbow. J Bone Joint Surg Br, 78(1), 128-132.
Verma, N. N., Bhatia, S., Baker, C. L., Cole, B. J., Boniquit, N., Nicholson, G. P., et al.
(2010). Outcomes of arthroscopic rotator cuff repair in patients aged 70 years or
older. Arthroscopy: the Journal of Arthroscopic and Related Surgery, 26(10),
1273-1280.
57
Virchenko, O., & Aspenberg, P. (2006). How can one platelet injection after tendon injury
lead to a stronger tendon after 4 weeks? Interplay between early regeneration and
mechanical stimulation. Acta Orthop, 77(5), 806-812.
Werthel, J. D., Pelissier, A., Massin, P., Boyer, P., & Valenti, P. (2014). Arthroscopic
double row cuff repair with suture-bridging and autologous conditioned plasma
injection: Functional and structural results. Int J Shoulder Surg, 8(4), 101-106.
Yamada, N., Hamada, K., Nakajima, T., Kobayashi, K., & Fukuda, H. (2000).
Comparison of conservative and operative treatments of massive rotator cuff
tears. Tokai J Exp Clin Med, 25(4-6), 151-163.
Yamaguchi, K., Levine, W. N., Marra, G., Galatz, L. M., Klepps, S., & Flatow, E. L.
(2003). Transitioning to arthroscopic rotator cuff repair: the pros and cons. Instr
Course Lect, 52, 81-92.
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CHAPTER 3
PAPER 1
Do postoperative platelet-rich plasma injections accelerate early tendon healing
and functional recovery after arthroscopic supraspinatus repair?
A randomized controlled trial
Allan Wang,1 PhD, FRACS, Philip McCann,2 FRCS (Tr&Orth), Jessica Colliver,3 BSc,
Eamon Koh,4 FRANZCR, Timothy Ackland,3 PhD, Brendan Joss,3 PhD, Minghao
Zheng,1 PhD, and Bill Breidhal, 5 FRANZCR.
1Department of Orthopaedic Surgery, University of Western Australia, Crawley,
Australia.
2Department of Trauma and Orthopaedic Surgery, Bristol Royal Infirmary, Bristol,
United Kingdom.
3School of Sport Science, Exercise and Health, University of Western Australia,
Crawley, Australia
4Department of Radiology, Fremantle Hospital, Fremantle, Australia
5Perth Radiological Clinic, Perth, Australia
ABSTRACT
Background: Tendon bone healing after rotator cuff repair directly correlates with a
successful outcome. Biological therapies that elevate local growth factor concentrations
may potentiate healing following surgery.
Purpose: To ascertain whether postoperative and repeated application of platelet-rich
plasma (PRP) to the tendon repair site improves early tendon healing and enhances early
functional recovery following double row arthroscopic supraspinatus repair.
Study Design: Randomized controlled trial; Level of evidence, 1.
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Methods: Sixty patients underwent arthroscopic double row supraspinatus tendon repair.
Following randomization, half the patients received two ultrasound-guided injections of
PRP to the repair site at day 7 and day 14 post-surgery. Early structural healing was
assessed with Magnetic Resonance Imaging (MRI) at 16 weeks and cuff appearances
graded according to the Sugaya classification. Functional scores were recorded with the
Oxford Shoulder Score (OSS), the Quick Disability of the Arm, Shoulder and Hand
(Quick-DASH), Visual Analogue Scale (VAS) for pain and Short From-12 (SF-12)
quality of life score both pre-surgery and post-operatively at 6, 12 and 16 weeks,
isokinetic strength and active range of motion was measured at 16 weeks.
Results: PRP treatment did not improve early functional recovery, range of motion,
strength or influence pain scores at any time point after arthroscopic suprapinatus repair.
There was no difference in MRI structural integrity of the supraspinatus repair between
groups (p=0.35) (PRP group 0% full thickness re-tear; 23% partial tear; 77% intact),
compared with the control group (7% full thickness re-tear; 23% partial tear; 70% intact)
at 16 weeks post-operatively.
Conclusion: Following arthroscopic supraspinatus tendon repair, image guided PRP
treatment on two occasions does not improve early tendon bone healing or functional
recovery.
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INTRODUCTION
Despite the advent of new surgical techniques to improve rotator cuff fixation to bone,
failure of the tendon repair often occurs (Galatz, et al., 2004; Sugaya, et al., 2007).
Tendon re-tears may be due to a specific re-injury at the repair site, but also may reflect
incomplete or failed primary healing after surgery (Boileau, et al., 2005; Carpenter, et al.,
1998).
Sonnabend, et al. (2010) in a primate model of rotator cuff repair, showed that a
significant proportion of Sharpey fibres begin to reconstitute at 3 months with maturation
at 4 months after surgery. Thus the early tendon healing stage is critical for long-term
success of rotator cuff repair. Accelerated rotator cuff rehabilitation programs which
allow active exercises sooner than 3 to 4 months before early tendon bone healing occurs,
risk early failure (Parsons, et al., 2010; Zhang, et al., 2013).
Hence, there has been increasing interest in adjuvant biological therapies to improve early
primary tendon healing. In particular, many studies have investigated platelet-rich
plasma (PRP) products, where a supra physiological concentration of platelets is
delivered to the tendon-bone repair site at the time of surgery. Activated platelets
degranulate to release multiple growth factors that modulate the cascade of chemotaxis,
cell proliferation and differentiation, which assist in the tendon healing process (Bedi, et
al., 2012; Eppely, et al., 2004; Galatz, et al., 2007; Gulotta & Rodeo, 2009; Isaac, et al.,
2012; Kobayashi, et al., 2006; Manning, et al., 2011; Molloy, et al., 2003; Plate, et al.,
2013).
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Published studies reporting the use of PRP administration have met with mixed success
in improving outcomes after rotator cuff repair. Appraisal of the literature is complicated
by the range of treated pathologies, varying from small, single tendon tears to massive
multitendon tears; concomitant use of acromioplasty or not; (Castricini, et al., 2011; Jo,
et al., 2011) and the formulation of PRP used, which ranged from intra-tendon injection
(Kesikburun, et al., 2013; Randelli, et al., 2008), spray application (Randelli, et al., 2008;
Ruiz-Moneo, et al., 2013), or incorporation of a platelet-rich fibrin matrix (PRFM) into
the tendon repair site (Barber, et al., 2011; Castricini, et al., 2011; Gumina, et al., 2012;
Weber, et al., 2013).
A further variable affecting the efficacy of PRP is the timing of delivery. All previous
PRP augmented rotator cuff studies to date have used time zero delivery at the time of
surgical repair. Following activation, platelets release growth factors almost immediately
with total elution within 1 hour (Arnoczky, et al., 2011), and the half-life of growth factors
is a matter of minutes to hours (Mooren, et al., 2010), however it has been acknowledged
that biological augmentation of tendon repairs too early in the tendon healing cascade
may be ineffective (Gulotta & Rodeo, 2009). Differing classes of growth factors are
active at specific time points (Kobayashi, et al., 2006); for example, animal studies have
shown that application of platelet-derived growth factors at day-7 have a more
pronounced effect on tendon cellular maturation and biomechanical strength than earlier
application (Chan, et al., 2006). Growth factors including BMP-13, platelet-derived
growth factor-B and transforming growth factor B1 are expressed maximally at days 7
and 14 (Wurgler-Hauri, et al., 2007) and the cytokine mediated temporal expression of
collagen type I and III increases from day-7 onward (Dahlgren, et al., 2005).
62
Hence, timing for PRP delivery remains an important consideration for optimizing tendon
healing. In this study we hypothesized that delayed and repeated injection of PRP at days
7 and 14 after surgery would firstly avoid the potential dilution and washout effect of
arthroscopic administration and secondly, produce a sustained up regulation of the tendon
healing process. The purpose of this study is to determine if this PRP delivery protocol
would enhance early tendon healing and functional recovery after arthroscopic
supraspinatus tendon repair. The primary study outcome is improved early tendon
healing as assessed by MRI scanning. The secondary outcome is patient rated function
as a measure of functional recovery.
METHODS
Patient Selection
Institutional Ethics Committee approval was granted for this study. Patients with MRI or
ultrasound proven rotator cuff tears were identified over the period from November 2011
to February 2013. A power calculation was performed to determine the required number
of patients to detect a significant difference of one Sugaya grade classification between
the treatment and control groups based on previously published MRI classification scores
for post-rotator cuff repair patients (Sugaya, et al., 2007). The power analysis used an
effect size of 0.769 (moderate effect), with significance of p<0.05 and a power of 80%,
giving a minimum sample size of 56 participants (28 participants in each group). More
participants (n=60) were recruited to allow for attrition.
The inclusion criteria comprised the presence of a symptomatic full thickness tear of
supraspinatus in an active adult identified by preoperative imaging and confirmed by
63
arthroscopic evaluation. All patients also received a series of plain radiographs
(anteroposterior, outlet and axillary views) for evaluation of arthritic change. Exclusion
criteria included: patients with a history of previous rotator cuff surgery, subscapularis or
infraspinatus tear identified on preoperative imaging or arthroscopic evaluation; labral
tear; significant degenerative glenohumeral osteoarthritis; contralateral shoulder
symptoms; rheumatalogical, neuromuscular or autoimmune disease; cervical disc
herniation; ongoing workers compensation claims; or contraindication to postoperative
MRI evaluation (Figure 1).
64
Figure 1. CONSORT (Consolidated Standards of Reporting Trials) flowchart.
PASTA = partial articular supraspinatus tendon avulsion; US = ultrasound; PRP =
platelet-rich plasma
Analysed (n=30)
Excluded from analysis (n=0
Analysed (n=30)
Excluded from analysis (n= 0)
Analysis
Lost to follow-up (n=0) Discontinued intervention (n=0)
Lost to follow-up (n=0) Discontinued intervention (n=0)
Follow-Up
Allocated to arthroscopic double row rotator cuff repair without postoperative US-guided PRP injections (n=30) Received allocated intervention (n=30) Did not receive allocated intervention (n= 0)
Allocated to arthroscopic double row rotator cuff repair and postoperative US-guided PRP injections (n=30)
Received allocated intervention (n=30)
Did not receive allocated intervention (n=0)
Allocation
Randomized (n=60)
Assessed for eligibility (n=305)
Excluded (n=239) Workers Compensation = 108 PASTA repairs = 31 Greater than 2cm, not
supraspinatus alone, or involving subscapularis/infraspinatus=73
Osteoarthritis (Glenohumeral joint)=27
Declined to participate (n=6)
Enrollment
65
Surgical Technique
All surgery was performed by the senior author. All procedures were performed in the
lateral decubitus position under general anaesthesia with an interscalene nerve block. The
arm was placed in 4 kg of traction and positioned in 30 degrees of arm flexion and
abduction. Initial diagnostic glenohumeral arthroscopy was performed and the presence
of a full thickness supraspinatus tear confirmed. After debridement of the bursal tissue
and tendon margins, the tear morphology was assessed and tear size measured with a
calibrated probe with 5 mm increments. Tears over 20 mm in the anterioposterior
dimension were excluded, as were partial tears. Supraspinatus tears associated with
subscapularis or infraspinatus tears were excluded from the study. Following
acromioplasty, rotator cuff reconstruction was performed. The footprint was prepared
with a full-radius resector to decorticate the greater tuberosity. A double row suture
bridge repair (Park, et al., 2006) with bioabsorbable anchors was performed (Arthrex Bio-
Corkscrew 5.5mm FT, Biocomposite Pushloc 3.5mm, Arthrex, Naples, FL, USA). The
same reconstructive technique was utilized in each case. Concomitant shoulder
pathology was treated as clinically or radiographically indicated. Acromioclavicular joint
arthropathy was treated with arthroscopic excision of the lateral end of the clavicle and
long head of biceps tendinopathy was treated with tenotomy (Table 1).
66
Table 1. Group demographics with concomitant procedures and complications a
PRP Group (n=30) Control Group (n=30)
Sex (male/female) 11/19 17/13
Mean age (years) [range] 59.8 [28-77] 58.4 [38-76]
Acromioplasty (n) 30 30
Biceps tenotomy (n) 3 5
Acromioclavicular joint excision (n) 4 5
Complications (n) 0 0
Supraspinatus tear size (mm) 14.60 (3.78) 13.70 (3.27)
a PRP = Platelet Rich Plasma.
Post-operative Protocol
All patients were immobilized in a sling (Ultrasling III, Don Joy, Carlsbad, CA, USA)
for 6 weeks postoperatively and followed a standard rehabilitation program under the
supervision of physical therapists. This consisted of passive range of motion exercises in
the first 6 weeks, followed by active assisted range of motion exercises from 6 to 10
weeks and finally, a guided strengthening program from 10 to 16 weeks. All patients
followed this program consistently.
Randomisation Procedure
Patients were reviewed on the fifth post-operative day, and following arthroscopic
evaluation and confirmation study inclusion criteria were met, randomized to PRP or
control groups. A computer block permutation method was prepared to generate a simple
randomised computer-generated table of blocks of 10 (5 PRP; 5 Control), stratified by
the treating surgeon at the five day post-surgical follow up. Sixty consecutive patients
meeting the study inclusion criteria, and consenting to the study were randomized via the
67
above procedure, with thirty in each arm of the study. The average age was 59.1 years
(range: 28-77 years). Patient demographics along with details of concomitant surgical
procedures are illustrated in Table 1.
Preparation of Platelet–rich Plasma
The group randomized to the treatment arm of the study underwent ultrasound guided
PRP injection to the rotator cuff repair site on two separate occasions, at days 7 and 14
post-surgery. The platelet concentrate was obtained using the Arthrex Autologous
Conditioned Plasma (ACP) system (Arthrex, Naples, FL, USA). A PRP injection was
prepared from 10 ml of autologous peripheral blood. Following the addition of 1 ml of
Anticoagulant Citrate Dextrose Solution (ACD-A), the blood was spun in a centrifuge
(ROTOFIX 32 A, Andreas Hettich GmbH & Co. KG, Tuttlingen, Germany) at 1500
revolutions per minute (RPM) for 5 minutes. Following centrifugation, the PRP
supernatant (approximately 2-4 ml) was removed and stored in a separate sterile syringe
in preparation for point of care delivery.
The ACP system produces a platelet concentration of approximately 470,000
platelets/μL, (2.1 times greater than the level in whole blood) with an estimated
concentration of growth factor reported as five to 25 times that of normal physiologic
levels. It is free of both residual erythrocytes and leucocytes, which may impair local
growth factor activity by free radical activation (Jiang, et al., 2007; Scott, et al., 2004).
Immediately prior to injection, the preparation was activated with 2 ml of CaCl2
(Nikolidakis & Jansen, 2008). The injection was delivered at the tendon repair site under
direct visualisation with ultrasound by an experienced fellowship-trained musculoskeletal
68
radiologist. Needle placement was aided by the identification of the echogenic sutures at
the tendon repair site (Figure 2). The control group did not receive a placebo injection.
Figure 2. Ultrasound image of needle placement directly at the tendon repair site (arrow).
Outcome Assessments
Radiographic analysis was performed with MR imaging at 16 weeks. All scans utilized
a 1.5 Telsa unit (Sonata Maestro Class; Siemens, Erlangen, Germany) with 40 mT/m
gradient power. Multiple images were obtained in oblique coronal, oblique sagittal and
axial planes with both short-tau inversion recovery (STIR) and turbo spin echo (TSE) T1-
weighted sequence. MRI assessment was performed by an experienced fellowship
trained musculoskeletal radiologist, who had not performed the PRP injections and was
blinded to patient allocation to treatment or control group. Multiple images were
evaluated and graded as per the Sugaya classification (Figure 3) (Sugaya, et al., 2007).
69
Figure 3. T1-weighted coronal magnetic resonance image displaying Sugaya grade 1
appearance.
Outcomes were assessed clinically and radiologically. Patients were assessed using the
Oxford Shoulder Score (OSS), Quick Disability of the Arm, Shoulder and Hand (Quick
DASH), Visual Analogue Scale (VAS) for pain and Short Form-12 (SF-12); pre-surgery
and at 6, 12 and 16 weeks post-surgery. All assessors were blinded as to the identity of
he treatment and control groups, nor were they involved in any stage of the recruitment
or surgery.
Active range of motion was assessed at 16 weeks using a goniometer. Absolute values
were recorded for arm flexion, abduction and external humeral rotation in both the
operated and un-operated shoulders, using anatomical landmarks for accuracy and
consistency. Range of motion was performed within the participants’ pain tolerance to
minimise any injury risk and discomfort.
70
Isokinetic strength was also assessed at 16 weeks with the patient seated in a Biodex
Isokinetic Dynamometer (Biodex, System 4, Shirley, NY) and a series of standardized
measurements performed with the patient instructed to produce a maximum muscular
force at speeds of 60 and 90 degrees/s. External humeral rotation was performed in the
modified-neutral position, with the elbow at 90 degrees of flexion and the forearm in a
neutral position throughout. Arm flexion was performed with the elbow fully extended.
Values for both peak torque and total work performed over the range of motion were
noted. Data were recorded as both absolute values and as a percentage of the scores
obtained on the contralateral, un-operated shoulder. A difference of 10-15% in the
strength between shoulders is regarded as physiologically normal in the general
population and in those patients undergoing surgery (Bigoni, et al., 2009).
Statistical Analysis
Values are presented as means with associated standard deviations. A series of two-
factor, repeated measures ANOVA was performed to assess for difference between the
treatment and control groups over time for continuous variables. For continuous data
recorded at a single time point only, a series of independent t-tests were performed,
whereas a Mann-Whitney U test was employed for the MRI rating primary outcome
variable. Statistical analyses used SPSS software (SPSS, Chicago, IL). For all tests, a
p<0.05 was considered significant.
RESULTS
All patients complied with the study protocol, and no patient was lost to follow up. There
were no significant complications such as infection, neurological or vascular deficit for
71
any patient in either arm of the study. In the control group mean tendon tear size treated
was 1.37 cm, and in the PRP group, mean tendon tear size treated was 1.46 cm. The
adjunctive procedures of acromioclavicular joint excision and biceps tenotomy are shown
in Table 1. No patient underwent a cortisone injection for pain, capsulitis or bursitis
within the study period.
Structural Evaluation
Using the Sugaya classification, the grade of supraspinatus tendon healing for the PRP
and control group is reported in Table 2. In both groups, 23% of subjects had a partial
thickness tendon repair (Sugaya grade 3). No full thickness re-tears were noted in the
PRP treatment group, two (7%) full thickness re-tears (Sugaya grades 4 and 5) occurred
in the control group. One patient in the PRP treatment group did not tolerate the
postoperative MRI scan and so underwent an ultrasound performed by an experienced
musculoskeletal radiologist. This tendon repair was intact and without any evidence of
thinning or discontinuity and so, for the purposes of the study, was included in the grade
1 group of that cohort. In the PRP treatment group, 23 subjects (77%) exhibited a healed
repair or an intact repair with high signal intensity (Sugaya grades 1 and 2), compared to
21 subjects (70%) in the control group. A Mann-Whitney U test demonstrated no
difference (p=0.351) between groups on MRI rating at 16 weeks (PRP group mean ± SD
= 1.8 ± 0.8; Control = 2.1 ± 1.0).
72
Table 2. Sugaya classification of MRI scans of patient treatment groups a
Sugaya Classification b Group Number Percentage
Grade 1 (no tear)
PRP 12 40.0
Control 9 30.0
Grade 2 (sufficient tendon thickness
but with high signal change)
PRP 11 36.6
Control 12 40.0
Grade 3 (insufficient thickness but
no tendon discontinuity)
PRP 7 23.0
Control 7 23.0
Grade 4 (small full thickness re-
tear)
PRP 0 0
Control 1 3.3
Grade 5 (large full thickness re-
tear)
PRP 0 0
Control 1 3.3
a Values are reported as n (%), PRP = platelet-rich plasma.
b From Sugaya, et al., (2007). Grade 1 = no tear; grade 2 = sufficient tendon thickness but with high signal
change; grade 3 =insufficient thickness but no tendon discontinuity; grade 4 = small full-thickness re-tear;
grade 5 = large full-thickness re-tear.
Functional Scores
Outcome scores for all patients improved following surgery. At 12 and 16 weeks
postoperatively, the OSS (F=75.803; df 3; p<0.001), the QuickDASH (F=53.939; df 3;
p<0.001) and the VAS pain scores (F=75.499; df 3; p<0.001) all improved significantly
from pre-surgery. Similarly, the SF-12 quality of life indicators improved with time:
Physical Component score (F=13.967; df 3; p<0.001) and Mental Component score
(F=5.401; df 3; p=0.001). There was, however, no statistical difference (p>0.05) between
the PRP treatment and control groups for any of these functional scores at any time point
postoperatively (Table 3).
73
Table 3. Functional scores a
Variable Group
Pre-surgery 6 weeks
post-surgery
12 weeks
post-surgery
16 weeks
post-surgery
Mean SD Mean SD Mean SD Mean SD
QuickDASH
Symptoms
PRP 42.27 17.06 51.17 19.54 33.14 19.27 22.58 14.36
Control 37.16 20.38 53.48 13.27 36.33 17.40 17.23 13.56
VAS PRP 6.37 1.59 3.26 2.43 2.35 2.01 1.75 1.68
Control 5.38 2.43 1.19 2.34 2.23 1.91 1.36 1.51
OSS PRP 27.63 6.90 23.57 9.61 33.38 8.93 38.17 7.19
Control 30.68 7.76 21.48 6.61 32.53 6.92 40.37 5.12
SF-12 PCS PRP 35.17 8.43 36.31 7.40 38.73 7.06 41.78 8.34
Control 37.92 7.97 34.98 5.75 39.08 6.94 43.08 6.26
SF-12 MCS PRP 52.16 12.24 49.87 12.94 52.75 11.90 53.81 11.21
Control 50.47 12.56 49.69 13.63 53.47 10.55 55.17 7.41
a Values are reported as mean ± SD. MCS = mental component score; OSS = Oxford Shoulder Score;
PCS = physical component score; PRP = platelet-rich plasma; QuickDASH = Quick Disability of the
Arm, Shoulder and Hand; SF-12 = Short Form-12; VAS = visual analogue scale for pain.
Strength
Isokinetic strength values were obtained for active arm flexion and external rotation
movements at two speeds. Values were expressed as a percentage of the strength
recorded in the contralateral shoulder. Within the control group the relative scores for
arm flexion peak torque at 90 and 60 degrees/s were 68.7% and 75.4% respectively, and
75.6% and 74.0% respectively for external rotation peak torque. Relative scores were
similar in the PRP treatment group for arm flexion peak torque at 90 and 60 degrees/s
(74.1% and 76.3%) and external rotation peak torque (72.1% and 77.3%) respectively.
No group differences (p>0.05) for strength scores at 16 weeks post-surgery were evident
(Table 4).
74
Table 4. Group mean scores (as percentage of the contralateral, un-operated arm) and t-
test results for strength measures at 16 weeks post-surgery a
Variable Group Mean (%) SD t P
Arm flexion peak torque 90°/s
PRP 74.1 10.8
-0.122 0.266
Control 68.7 24.2
Arm flexion total work 90°/s
PRP 55.5 23.2
0.107 0.915
Control 56.3 34.2
Arm flexion peak torque 60°/s
PRP 76.3 22.0
-0.190 0.85
Control 75.4 22.0
Arm flexion total work 60°/s
PRP 61.7 21.8
-0.150 0.881
Control 60. 8 27.4
External rotation peak torque 90°/s
PRP 72.2 15.7
0.470 0.640
Control 75.6 37.5
External rotation total work 90°/s
PRP 51.9 30.1
0.712 0.371
Control 55.1 35.8
External rotation peak torque 60°/s
PRP 77.3 17.8
-0.64 0.525
Control 74.0 21.3
External rotation total work 60°/s
PRP 59.8 24.3
0.277 0.783
Control 62.3 44.0
a Strength was calculated as a percentage of the contralateral, un-operated arm. Results are reported as
mean ± SD, PRP = platelet-rich plasma.
Range of Motion
The analysis revealed no significant differences (p>0.05) in any active range of motion
measure between the two groups at 16 weeks post-surgery. Complete values are
displayed in Table 5.
75
Table 5. Group mean scores and t-test results for range of motion for the operated limb
at 16 weeks post-surgery a
Range of Motion
(degrees) Group
Mean
(deg) SD t P
Arm flexion 1.274 0.208
PRP 144.8 22.8
Control 151.8 19.8
Arm abduction 0.342 0.734
PRP 134.8 28.2
Control 137.4 29.1
External rotation 0.69 0.493
PRP 41.1 10.2
Control 42.8 9.3
a PRP = platelet-rich plasma
DISCUSSION
The purpose of the study was to evaluate the efficacy of a protocol of sequential PRP
administration following arthroscopic supraspinatus repair. All previous studies have
utilized a single delivery of a PRP product at the time of surgery. The current protocol
delivered a PRP product under ultrasound guidance to the tendon repair site at 7 and 14
days after surgery to avoid a possible dilution or washout effect of PRP, which may occur
with arthroscopic fluid lavage. This protocol also allows a potentially prolonged up-
regulation of growth factors involved in the tendon-healing cascade. Our hypothesis was
that this post-surgical and sequential PRP delivery protocol would firstly improve rotator
cuff healing and secondly accelerate early functional recovery following arthroscopic
rotator cuff repair.
This study finds that at 16 weeks post-surgery, no full thickness tendon re-tears occurred
in the PRP group however, there were two (7%) full thickness re-tears in the control
76
group. Although this difference was not statistically significant, our findings are
consistent with previous reports. Castricini, et al. (2012) examined the effects of PRFM
augmentation in rotator cuff repair and reported the re-rupture rate was higher in the
control group (10.5% versus 2.5%). In contrast, Gumina, et al. (2012), using a novel
platelet rich fibrin matrix allowing slow release of growth factors on the tendon repair
site, found a 14% re-tear rate in isolated supraspinatus tears (between 2 to 4 cm) in the
PRP group compared to 50% in the control group at 13 months. However Rodeo, et al.
(2007), also using PRFM in 79 patients undergoing arthroscopic cuff repair found no
difference in tendon bone healing on ultrasound at 6 weeks and 12 weeks after surgery.
The secondary outcomes of this study were to evaluate early functional recovery in
patients receiving PRP treatment following supraspinatus repair. In a prospective RCT
of 53 patients, Randelli, et al. (2011) reported that PRP administered by spray, produced
statistically better early function scores and strength at 3 months post-surgery. No
imaging was performed at this stage, though it was concluded that PRP administration
accelerates early recovery following surgery. Zumstein, et al. (2012) also showed an early
benefit of PRP administration with improved revascularization of the tendon-bone repair
site. Doppler ultrasonography was used to assess the vascularization index of 20
shoulders at 6 and 12 weeks following surgery (Zumstein, et al., 2012). At 6 weeks, those
shoulders treated with a leucocyte rich PRP product showed significantly better
vascularization, however this was not sustained at 12 weeks.
Our study can report that early functional recovery was not improved with a sequential
post-surgical PRP delivery protocol. At 6, 12 and 16 weeks, clinical function scores were
equivalent between PRP and control group participants. Furthermore, objective testing
of shoulder function at 16 weeks showed no difference between groups in recovery of
77
active arm flexion, abduction, or external rotation range of motion. Similarly, isokinetic
peak torque and the work done through the active range of motion during each movement
was not different between groups.
PRP delivery by injection under ultrasound guidance into the supraspinatus tendon repair
site may be less accurate than injection under arthroscopic visualization. However, the
surgical technique employed in this study comprised a double row suture bridge technique
and the echogenic suture knots were readily identified on ultrasound. Moreover, the
oblique and interlocking sutures of the suture bridge potentially retains the injected PRP
at the repair site better than the single row repair site technique used in previous studies
(Randelli, et al., 2011).
As an imaging modality, ultrasound has been shown to be reliable in obtaining a precise
placement of PRP at the site of tendon injury (Wiegerinck, et al., 2011). PRP delivery by
direct injection under ultrasound guidance has been used to treat injuries of the Achilles
tendon (de Vos et al., 2010), the common extensor tendon origin (Mishra, et al., 2006;
Mishra, et al., 2014; Peerbooms, et al., 2010) and the rotator cuff. Kesikburun, et al.
(2013) demonstrated that PRP injection to non-surgically treat rotator cuff tendinopathy
and partial thickness tendon tears has no significant clinical benefit over saline injections
at 3, 6, 12 and 52 weeks. The findings of our study are consistent with this work, and
even with a second PRP injection, there was no significant clinical or functional benefit
up to 16 weeks post-surgery. Our study focus is early outcomes, however definitive
clinical outcomes require 12 to 24 month postoperative evaluation.
This study has some limitations to be acknowledged. Firstly, the follow-up was limited
to 16 weeks. It is possible that more structural tendon failures would have been seen if
78
MRI evaluation was repeated at a later time interval such as 12 months. However, it was
the primary aim of this study to assess the effects of PRP treatment on the early phases
of tendon healing. Animal models have demonstrated that a significant proportion of
Sharpey’s fibres at the tendon repair site have reconstituted and matured at the bone-
tendon repair by 3 to 4 months (Sonnabend, et al., 2010), thus supporting the validity of
assessment at the 16-week time point.
A second limitation is the non-blinding of subjects in both PRP and control groups. As
the study protocol required two separate post-surgical injections, we considered that it
would be impractical to have patients agreeing to complete two placebo injections.
Patients in the PRP treatment group may have had the benefit of a placebo as well as a
possible PRP treatment effect in their clinical and functional evaluation. Similarly, those
patients who did not receive injections may have responded differently in clinical testing.
The non-blinding of subjects could be expected to cause a positive bias in the PRP group
however, groups were equivalent in their study outcomes. MRI evaluation was performed
by an independent musculoskeletal radiologist, who had not been involved in previous
diagnostic imaging or PRP injections, and was blinded to group allocation.
A further possible study limitation was the PRP product used in this study, does not
achieve the very high concentration of platelets reported with some other PRP products
(Arnoczky, et al., 2011; Eppely, et al., 2004; Geaney, et al., 2011). Sundman, et al.
(2011), in a laboratory study suggested that markedly elevated supra physiological levels
of platelets and growth factors may be of no additional benefit due to cell-surface receptor
saturation, or may actually be detrimental to tendon healing. Optimal tendon healing
requires not only the appropriate concentration of growth factors, but those growth factors
79
be delivered at the appropriate time in the tendon healing cascade, to be maximally
effective.
CONCLUSION
This study is the first to evaluate the efficacy of a post-surgical PRP delivery protocol to
improve healing and functional outcomes after arthroscopic rotator cuff repair.
Sequential delivery of the specific injectable PRP preparation used in this study under
ultrasound guidance, at days 7 and 14 post-surgery, does not improve early rotator cuff
healing or functional recovery. Future research should include randomized controlled
trials of other PRP products with alternate delivery vehicles and dosing regimes.
REFERENCES
Arnoczky, S. P., Delos, D., & Rodeo, S. A. (2011). What is Platelet-Rich Plasma?
Operative Techniques in Sports Medicine, 19(3), 142-148.
Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing
influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the
Journal of Arthroscopic and Related Surgery, 27(8), 1029-1035.
Bedi, A., Maak, T., Walsh, C., Rodeo, S. A., Grande, D., Dines, D. M., et al. (2012).
Cytokines in rotator cuff degeneration and repair. J Shoulder Elbow Surg, 21(2),
218-227.
Bigoni, M., Gorla, M., Guerrasio, S., Brignoli, A., Cossio, A., Grillo, P., et al. (2009).
Shoulder evaluation with isokinetic strength testing after arthroscopic rotator
cuff repairs. Journal of Shoulder and Elbow Surgery, 18, 178.
80
Boileau, P., Brassart, N., Watkinson, D. J., Carles, M., Hatzidakis, A. M., & Krishnan,
S. G. (2005). Arthroscopic repair of full-thickness tears of the supraspinatus:
does the tendon really heal? . Journal of Bone and Joint Surgery (Am), 87(6),
1229-1240.
Carpenter, J. E., Thomopoulos, S., Flanagan, C. L., De Bano, C. M., & Soslowsky, L. J.
(1998). Rotator cuff defect healing: a biomechanic and histologic analysis in an
animal model. . Journal of Shoulder and Elbow Surgery, 7(6), 599-605.
Castricini, R., Longo, U. G., De Benedetto, M., Panfoli, N., Pirani, P., Zini, R., et al.
(2011). Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a
randomized controlled trial. Am J Sports Med, 39(2), 258-265.
Chan, B. P., Fu, S. C., Qin, L., Rolf, C., & Chan, K. M. (2006). Supplementation-time
dependence of growth factors in promoting tendon healing. Clin Orthop Relat
Res, 448, 240-247.
Dahlgren, L. A., Mohammed, H. O., & Nixon, A. J. (2005). Temporal expression of
growth factors and matrix molecules in healing tendon lesions. J Orthop Res,
23(1), 84-92.
de Vos, R. J., Weir, A., van Schie, H. T., Bierma-Zeinstra, S. M., Verhaar, J. A.,
Weinans, H., et al. (2010). Platelet-rich plasma injection for chronic Achilles
tendinopathy: a randomized controlled trial. JAMA, 303(2), 144-149.
Eppely, B. L., Woodell, J. E., & Higgins, J. (2004). Platelet quantification and growth
factor analysis from platelet-rich plasma: implications for wound healing.
Plastic and Reconstructive Surgery, 114(6), 1502-1508.
Galatz, L. M., Ball, C. M., Teefey, S. A., Middleton, W. D., & Yamaguchi, K. (2004).
The outcome and repair of completely arthroscopically repaired large and
massive rotator cuff tears. . Journal of Bone and Joint Surgery (Am), 86(2), 219-
224.
81
Geaney, L. E., Arciero, R. A., De Berardino, T. M., & Mazzocca, A. D. (2011). The
effects of platelet-rich plasma on tendon and ligament: Basic science and clinical
application. Operative Techniques in Sports Medicine, 19(3), 160-164.
Gulotta, L. V., & Rodeo, S. A. (2009). Growth factors for rotator cuff repair. Clinical
Sports Medicine, 28, 13-23.
Gumina, S., Campagna, V., Ferrazza, G., Giannicola, G., Fratalocchi, F., Milani, A., et
al. (2012). Use of platelet-leukocyte membrane in arthroscopic repair of large
rotator cuff tears: a prospective randomized study. J Bone Joint Surg Am,
94(15), 1345-1352.
Isaac, C., Gharaibeh, B., Witt, M., Wright, V. J., & Huard, J. (2012). Biologic
approaches to enhance rotator cuff healing after injury. J Shoulder Elbow Surg,
21(2), 181-190.
Jiang, N., Tan, N. S., Ho, B., & Ding, J. L. (2007). Respiratory protein-generated
reactive oxygen species as an antimicrobial strategy. Nat Immunol, 8(10), 1114-
1122.
Jo, C. H., Kim, J. E., Yoon, K. S., Lee, J. H., Kang, S. B., Han, H. S., et al. (2011).
Does platelet-rich plasma accelerate recovery after rotator cuff repair? A
prospective cohort study. Am J Sports Med, 39(10), 2082-2090.
Kesikburun, S., Tan, A. K., Yilmaz, B., Yasar, E., & Yazicioglu, K. (2013). Platelet-
rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a
randomized controlled trial with 1-year follow-up. Am J Sports Med, 41(11),
2609-2616.
Kobayashi, M., Itoi, E., Minagawa, H., Miyakoshi, N., Takahashi, S., Tuoheti, Y., et al.
(2006). Expression of growth factors in the early phase of supraspinatus tendon
healing in rabbits. J Shoulder Elbow Surg, 15(3), 371-377.
82
Manning, C. N., Kim, H. M., Sakiyama-Elbert, S., Galatz, L. M., Havlioglu, N., &
Thomopoulos, S. (2011). Sustained delivery of transforming growth factor beta
three enhances tendon-to-bone healing in a rat model. J Orthop Res, 29(7),
1099-1105.
Mishra, A., & Pavelko, T. (2006). Treatment of chronic elbow tendonosis with buffered
platelet-rich plasma. Am J Sports Med, 34(11), 1174-1178.
Mishra, A. K., Skrepnik, N. V., Edwards, S. G., Jones, G. L., Sampson, S., Vermillion,
D. A., et al. (2014). Efficacy of platelet-rich plasma for chronic tennis elbow: a
double-blind, prospective, multicenter, randomized controlled trial of 230
patients. Am J Sports Med, 42(2), 463-471.
Molloy, T., Wang, Y., & Murrell, G. A. C. (2003). The roles of growth factors in
tendon and ligament healing. Sports Medicine, 33(5), 381-394.
Mooren, R. E., Hendriks, E. J., van den Beucken, J. J., Merkx, M. A., Meijer, G. J.,
Jansen, J. A., et al. (2010). The effect of platelet-rich plasma in vitro on primary
cells: rat osteoblast-like cells and human endothelial cells. Tissue Eng Part A,
16(10), 3159-3172.
Nikolidakis, D., & Jansen, J. A. (2008). The biology of platelet-rich plasma and its
application in oral surgery: literature review. Tissue Eng Part B Rev, 14(3), 249-
258.
Park, M. C., Elattrache, N. S., Ahmad, C. S., & Tibone, J. E. (2006). "Transosseous-
equivalent" rotator cuff repair technique. Arthroscopy, 22(12), 1360 e1361-
1365.
Parsons, B. O., Gruson, K. I., Chen, D. D., Harrison, A. K., Gladstone, J., & Flatow, E.
L. (2010). Does slower rehabilitation after arthroscopic rotator cuff repair lead to
long-term stiffness? J Shoulder Elbow Surg, 19(7), 1034-1039.
83
Peerbooms, J. C., Sluimer, J., Bruijn, D. J., & Gosens, T. (2010). Positive effect of an
autologous platelet concetrate in lateral epicondylitis in a double-blind
randomised controlled trial: platelet-rich lasma versus corticosteroid
injectionwith a 1-year follow-up. The American Journal of Sports Medicine,
38(2), 255-262.
Plate, J. F., Haubruck, P., Walters, J., Mannava, S., Smith, B. P., Smith, T. L., et al.
(2013). Rotator cuff injuries in professional and recreational athletes. J Surg
Orthop Adv, 22(2), 134-142.
Randelli, P., Arrigoni, P., Ragone, V., Aliprandi, A., & Cabitza, P. (2011). Platelet rich
plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year
follow-up. J Shoulder Elbow Surg, 20(4), 518-528.
Randelli, P. S., Arrigoni, P., Cabitza, P., Volpi, P., & Maffulli, N. (2008). Autologous
platelet rich plasma for arthroscopic rotator cuff repair. A pilot study. Disabil
Rehabil, 30(20-22), 1584-1589.
Rodeo, S. A., Potter, H. G., Turner, A. S., Him, H. J., & Atkinson, B. L. (2007).
Biologic augmentation of rotator cuff tendon healing using a mixture of
osteoinductive growth factors: an experimental study. . Journal of Bone and
Joint Surgery (Am), 87(6), 1229-1240.
Ruiz-Moneo, P., Molano-Munoz, J., Prieto, E., & Algorta, J. (2013). Plasma rich in
growth factors in arthroscopic rotator cuff repair: a randomized, double-blind,
controlled clinical trial. Arthroscopy, 29(1), 2-9.
Scott, A., Khan, K. M., Roberts, C. R., Cook, J. L., & Duronio, V. (2004). What do we
mean by the term "inflammation"? A contemporary basic science update for
sports medicine. Br J Sports Med, 38(3), 372-380.
84
Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-
594.
Sugaya, H., Maeda, K., Matsuki, K., & Moriishi, J. (2007). Repair integrity and
functional outcome after arthroscopic double-row rotator cuff repair. A
prospective outcome study. J Bone Joint Surg Am, 89(5), 953-960.
Sundman, E. A., Cole, B. J., & Fortier, L. A. (2011). Growth factor and catabolic
cytokine concentrations are influenced by the cellular composition of platelet-
rich plasma. Am J Sports Med, 39(10), 2135-2140.
Weber, S. C., Kauffman, J. I., Parise, C., Weber, S. J., & Katz, S. D. (2013). Platelet-
rich fibrin matrix in the management of arthroscopic repair of the rotator cuff: a
prospective, randomized, double-blinded study. Am J Sports Med, 41(2), 263-
270.
Wiegerinck, J. I., Reilingh, M. L., de Jonge, M. C., van Dijk, C. N., & Kerkhoffs, G. M.
(2011). Injection techniques of platelet-rich plasma into and around the Achilles
tendon: a cadaveric study. Am J Sports Med, 39(8), 1681-1686.
Wurgler-Hauri, C. C., Dourte, L. M., Baradet, T. C., Williams, G. R., & Soslowsky, L.
J. (2007). Temporal expression of 8 growth factors in tendon-to-bone healing in
a rat supraspinatus model. J Shoulder Elbow Surg, 16(5 Suppl), S198-203.
Zhang, Q., Ge, H., Zhou, J., & Cheng, B. (2013). Are platelet-rich products necessary
during the arthroscopic repair of full-thickness rotator cuff tears: a meta-
analysis. PLoS One, 8(7), e69731.
Zumstein, M. A., Berger, S., Schober, M., Boileau, P., Nyffeler, R. W., Horn, M., et al.
(2012). Leukocyte- and platelet-rich fibrin (L-PRF) for long-term delivery of
growth factor in rotator cuff repair: review, preliminary results and future
directions. Curr Pharm Biotechnol, 13(7), 1196-1206.
85
CHAPTER 4
PAPER 2
Early postoperative repair status after rotator cuff repair cannot be
accurately classified using questionnaires of patient function
and isokinetic strength evaluation.
PREAMBLE
Research conducted by Sonnabend and colleagues (2010), shows the reconstitution and
maturation of Sharpey fibres at 3-4 months post rotator cuff repair. Kluger, et al. (2011)
have shown that the majority of recurrent tears occurred in the first 3 months following
rotator cuff surgery, highlighting that this early tendon healing phase is critical for
longer term success. The early confirmation that tendon healing is progressing (or not),
is of benefit, and could affect post-surgery management (rehabilitation and/or revision
surgery), as well as individual structured return to work and/or sport. It is common to
introduce return-to-work strategies at 4 months post rotator cuff repair and therefore, we
believe that the prediction of tendon healing at this stage using low cost functional and
strength outcomes could prove beneficial.
The post-operative use of MRI and/or US to evaluate rotator cuff repair tendon healing
can be costly and time consuming. Studies have investigated the diagnostic accuracy of
common clinical shoulder tests for conservatively treated rotator cuff tendon tears, and
concluded that most tests are inaccurate and cannot be recommended for clinical
diagnosis (Ainsworth & Lewis, 2007; Hughes, et al., 2008; Murrell & Walton, 2001;
Hegedus, et al., 2008; 2012). This may well be the case post-operatively, and more
robust testing in this area is required (Hegedus, et al., 2008; 2012).
86
As the results of Wang, et al. (2015) showed no significant difference between the PRP
and control groups in structural tendon healing, function or strength outcomes, we saw
an opportunity to combine the original groups into one cohort, to further investigate this
gap in the research.
REFERENCES
Ainsworth, R., & Lewis, J. (2007). Exercise therapy for the conservative management
of full thickness tears of the rotator cuff: a systematic review. Br J Sports Med,
41, 200-210.
Hegedus, E. J., Goode, A., Campbell, S., Morin, A., Tamaddoni, M., Moorman, C. T.,
3rd, et al. (2008). Physical examination tests of the shoulder: a systematic
review with meta-analysis of individual tests. Br J Sports Med, 42(2), 80-92;
discussion 92.
Hegedus, E. J., Goode, A. P., Cook, C. E., Michener, L., Myer, C. A., Myer, D. M., et
al. (2012). Which physical examination tests provide clinicians with the most
value when examining the shoulder? Update of a systematic review with meta-
analysis of individual tests. Br J Sports Med, 46(14), 964-978.
Hughes, P. C., Taylor, N. F., & Green, R. A. (2008). Most clinical tests cannot
accurately diagnose rotator cuff pathology: a systematic review. Aust J
Physiother, 54(3), 159-170.
Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term
survivorship of rotator cuff repairs using ultrasound and magnetic resonance
imaging analysis. Am J Sports Med, 39(10), 2071-2081.
Murrell, G. A., & Walton, J. R. (2001). Diagnosis of rotator cuff tears. Lancet,
357(9258), 769-770.
87
Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-
594.
Wang, A., McCann, P., Colliver, J., Koh, E., Ackland, T., Joss, B., et al. (2015). Do
Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing
and Functional Recovery After Arthroscopic Supraspinatus Repair? A
Randomized Controlled Trial. Am J Sports Med (in press).
88
Early post-operative repair status after rotator cuff repair cannot be accurately
classified using questionnaires of patient function and isokinetic strength
evaluation.
Jessica A. Colliver BSc1; Allan W. Wang PhD, FRACS1,2; Eamon Koh FRANZCR3;
Brendan Joss PhD1; Jay R. Ebert PhD1; Timothy R. Ackland PhD1; William Breidahl,
FRANZCR4.
1 School of Sport Science, Exercise and Health, University of Western Australia, Crawley,
Perth, Western Australia.
2 Department of Orthopaedic Surgery, The University of Western Australia, Crawley,
Perth, Western Australia.
3 Department of Radiology, Fremantle Hospital, Fremantle, Western Australia.
4 Perth Radiological Clinic, Subiaco, Perth, Western Australia.
Level of Evidence: Level IV prospective study.
ABSTRACT
Purpose: To investigate if patients with an intact repair or partial re-tear in the early
stages (16 weeks) after rotator cuff repair surgery display differences in common shoulder
patient-reported outcome (PRO) measures and isokinetic strength tests, and whether early
post-surgical tendon healing could be predicted using these clinical shoulder evaluations.
Methods: This study was undertaken in 60 patients undergoing arthroscopic double-row
supraspinatus tendon repair. All patients were assessed clinically at 16 weeks post-
89
surgery using the Oxford Shoulder Score, the Quick Disability of the Arm, Shoulder and
Hand (QuickDASH), a Visual Analogue Pain Scale and the 12-item Short Form Health
survey, as well as isokinetic strength evaluation (external humeral rotation and arm
flexion). Magnetic Resonance Imaging (MRI) was undertaken at 16 weeks post-surgery.
Independent t-tests were employed to investigate clinical differences in patients group-
stratified based on the Sugaya MRI classification for rotator cuff tears (Grades 1, 2 or 3).
Discriminant analysis was employed to determine whether intact repairs (Sugaya Grade
1) and partial re-tears (Sugaya Grades 2 and 3) could be predicted based on clinical scores.
Results: No significant differences (p<0.05) in any of the PRO or strength measures were
observed between groups at 16 weeks post-surgery. Discriminant analysis revealed the
QuickDASH alone produced a 97% true positive rate for predicting partial re-tears, but
also a 90% false positive rate. The ability to discriminate between groups was enhanced
with up to five variables entered; however, only 87% of the partial re-tear group, and 36%
of the intact repair group, were correctly classified.
Conclusion: We observed no difference in clinical scores between patient groups
stratified by the Sugaya MRI classification system at 16 weeks post-surgery, while the
presence of an intact repair or partial re-tear after surgery could not be accurately
predicted by these shoulder evaluations. Our results suggest that correct classification of
tendon healing in the early stage following surgery must involve medical imaging.
Keywords: rotator cuff repair surgery, shoulder, patient-reported outcome measures,
isokinetic strength, magnetic resonance imaging.
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INTRODUCTION
Rotator cuff surgical repair is common with in excess of 250,000 performed each year
(Gulotta & Rodeo, 2009). However, despite several proposed surgical techniques and the
increasing use of adjunct biological therapies to stimulate and/or enhance repair, the post-
operative failure rate remains relatively high (Barber, et al., 2011; Charousset, et al.,
2010; Cheung, et al., 2010). It is well documented in the literature that increased patient
age, tear size and severity of pre-operative fatty muscular degeneration contribute to an
increased incidence of post-operative rotator cuff re-tears (Boileau, et al., 2005; Cho &
Rhee, 2009; Cho, et al., 2010; Galatz, et al., 2004; Murrell & Walton, 2001; Oh, et al.,
2010). While patients with re-tears or failed healing may experience a reduction in pain,
functional outcomes including strength levels are significantly lower when compared to
patients with evidence of healed tendons (Boileau, et al., 2005; Cho & Rhee, 2009;
Galatz, et al., 2004; Harryman, et al., 1991; Sugaya, et al., 2007). These inferior
functional results may be satisfactory for an older and/or less active population, but for
patients requiring a return to sport or work, especially in roles where physical strength is
important, many are likely to be dissatisfied with the outcome.
In a primate model of rotator cuff repair, it has been shown that a significant proportion
of Sharpey fibres start to reconstitute at 3 months, with maturation seen at four months
(Sonnabend, et al., 2010). Kluger, et al. (2011) reported that the majority of recurrent
tears occurred in the first three months after rotator cuff surgery, highlighting that this
early tendon healing phase up to 3-4 months post-operatively is critical for longer term
success. Early confirmation that healing is progressing well (or not) is therefore of
benefit, and could affect post-surgery management (rehabilitation and/or re-operation),
as well as the patient’s individualised structured return to work and/or sport. For the
91
aforementioned reasons, it is commonplace to introduce return-to-work strategies at four
months post-surgery and, therefore, prediction of tendon-healing at this stage using low
cost functional and strength outcomes could prove beneficial.
The use of post-operative magnetic resonance imaging (MRI) and/or ultrasound (US) to
evaluate the outcome of rotator cuff surgery can be costly and time consuming. Several
researchers have attempted to determine whether the healing progress of a conservatively
treated rotator cuff tendon tear can be predicted using common, clinical shoulder
assessments, albeit with limited success (Ainsworth & Lewis, 2007; Hughes, et al., 2008;
Murrell & Walton, 2001). At the time of writing, the authors are unaware of any other
studies that have investigated the ability of common shoulder clinical assessments to
predict the early post-operative success of rotator cuff repair surgery, independent of
radiological assessment (MRI and/or US).
Therefore, this study aimed to: a) investigate if differences in common shoulder patient-
reported outcome (PRO) measures and isokinetic strength tests could be observed
between patients with intact repairs or partial re-tears, classified by MRI, at 16 weeks
after rotator cuff repair surgery, and; (b) determine if early post-surgical tendon healing
could be predicted using these PRO measures and strength tests alone, without the need
for radiological assessment.
METHODS
Patients
Between November 2011 and February 2013, patients with rotator cuff tears isolated to
the supraspinatus, confirmed via US or MRI, were invited to participate in this project.
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This study was part of a larger, published randomized controlled trial (RCT) that sought
to ascertain whether platelet-rich plasma (PRP) applied to the tendon repair site after
double-row arthroscopic supraspinatus repair (PRP group), improved early tendon
healing and functional recovery, compared to no adjunct post-operative treatment (control
group) (Wang, et al., 2015). Therefore, inclusion and exclusion criteria for this RCT have
been published (Wang, et al., 2015). In brief, inclusion criteria required patients to have
a symptomatic full thickness tear of supraspinatus, confirmed pre-operatively via MRI or
US and intra-operatively by arthroscopic evaluation. Patients with supraspinatus partial
tears or tears over 20 mm in the anteroposterior dimension were excluded, as were
patients with concomitant subscapularis and/or infraspinatus tears identified on pre-
operative US/MRI or intra-operative examination. Patients were excluded if they had a
history of previous rotator cuff surgery, labral tearing, significant osteoarthritis of the
glenohumeral joint, rheumatalogical, neuromuscular or autoimmune disease and/or
cervical disc herniation. Patients were further excluded if they presented with any
contralateral shoulder symptoms or had ongoing workers’ compensation claims.
Over the study recruitment period, a total of 305 patients were assessed for study
eligibility. A CONSORT (Consolidated Standards of Reporting Trials) flowchart has
been previously published (Wang, et al., 2015). As part of the primary RCT, (Wang, et
al., 2015) all patients that consented to the study and subsequently underwent
supraspinatus repair, were reviewed on the fifth post-operative day and then randomized
by a computer block permutation method into either the PRP injection group or the
control group. Therefore, a total of 60 consecutive patients (30 PRP; 30 control) meeting
the study inclusion criteria and consenting to the study were randomized via the
aforementioned procedure. Patient demographics with concomitant surgical procedures
are presented in Table 1. A priori power calculation was performed for the primary RCT
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(Wang, et al., 2015) which indicated that for an anticipated moderate effect size of 0.769
in the primary outcome variable (the Sugaya classification system of rotator cuff tear
severity (Sugaya, et al., 2007)), a total of 56 patients (28 PRP; 28 control) were required
to reveal differences at the 5% significance level, with 80% power. Therefore, a total of
60 participants were initially recruited to allow for attrition. This research was approved
by the relevant Institutional Review Board (IRB).
Table 1. Group demographics with details of concomitant procedures and complications.
PRP Group (n=30) Control Group (n=30)
Sex (male/female) 11/19 17/13
Mean age (years) [range] 59.8 [28-77] 58.4 [38-76]
Acromioplasty (n) 30 30
Biceps tenotomy (n) 3 5
Acromioclavicular joint excision (n) 4 5
Complications (n) 0 0
Supraspinatus tear size (mm) 14.6 (3.8) 13.7 (3.4)
PRP = Platelet Rich Plasma.
Surgical Technique
All surgery was performed by the senior author and has been previously published (Wang,
et al., 2015). Briefly, all procedures were performed in the lateral decubitus position
under general anesthesia with an interscalene nerve block. The arm was placed in 4 kg
of traction and positioned in 30º of arm flexion and abduction. The presence of a full
thickness supraspinatus tear was initially confirmed via diagnostic glenohumeral
arthroscopy. Tear type and size were assessed using a calibrated probe with 5 mm
increments, following debridement of bursal tissue and tendon margins. After
94
acromioplasty, rotator cuff reconstruction was performed. The footprint was prepared
with a full-radius resector to decorticate the greater tuberosity. A double-row suture-
bridge repair (Park, et al., 2006) technique with bioabsorbable anchors was performed
(Arthrex Bio-Corkscrew 5.5 mm–FT, Biocomposite Pushloc 3.5 mm; Arthrex) in all
cases. Concomitant shoulder injuries were treated as clinically or radiographically
indicated. Acromioclavicular joint arthropathy was treated with arthroscopic excision of
the lateral end of the clavicle, and long head of biceps tendinopathy was treated with
tenotomy (Table 1).
Post-operative Management
All patients were immobilized in an abduction sling (Ultrasling III, Don Joy, Carlsbad,
CA, USA) for 6 weeks post-operatively and underwent a standard rehabilitation program
under the supervision of a physical therapist. Briefly, patients underwent an initial 6
weeks of passive range of motion exercises, followed by active-assisted range of motion
exercises from 6-10 weeks and a conservative strengthening program from 10-16 weeks.
All patients followed the aforementioned protocol consistently.
Patient-reported Outcome (PRO) Measures
Four PRO measures were employed pre- and post-operatively at 16 weeks, including: 1)
the Oxford Shoulder Score (OSS); 2) the Quick Disability of the Arm, Shoulder and Hand
(QuickDASH) questionnaire; 3) a Visual Analogue Pain Scale (VAS), and; 4) the 12-
item Short Form Health survey (SF-12). Firstly, the OSS is a 12-item questionnaire
evaluating pain and function, which has been validated against both general health and
clinical measures and has demonstrated good reliability in evaluating outcome after
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shoulder surgery (Dawson, et al., 1996; Dawson, et al., 2001; Olley & Carr, 2008). The
QuickDASH is an 11-item questionnaire evaluating pain, symptoms and physical
function in patients with upper limb musculoskeletal disorders, (Beaton, et al., 2005) and
has also demonstrated good reliability, validity and responsiveness (Beaton, et al., 2005;
Gummesson, et al., 2006). The VAS required patients to rate their pain intensity on a 0-
10cm sliding scale (0 = no pain, 10 = worst pain imaginable) in the preceding 24 hours.
A 1.4cm improvement on the VAS has previously been reported as the minimal clinically
important change in patients undergoing non-operative treatment for rotator cuff disease
(Tashjian, et al., 2009). Finally, the SF-12 is a generic health-related quality of life score,
(Ware, et al., 1996) that produces a physical (PCS) and mental (MCS) component
subscale.
Isokinetic Strength Evaluation
Isokinetic strength was assessed at 16 weeks post-surgery in all patients using a Biodex
Isokinetic Dynamometer (Biodex, System 4, Shirley, NY). Patients were seated with the
trunk stabilized using rigid straps, and adjustments made for humeral and forearm length,
in accordance with each patient’s stature. Patients were instructed to undertake maximal
concentric external/internal humeral rotation (Figure 1), followed by arm flexion, at an
angular velocity of 60°/s. External/internal humeral rotation was performed in the
modified-neutral position, with the elbow in 90° of flexion and the forearm in a neutral
position. Arm flexion was performed with the elbow fully extended. Each trial consisted
of three maximal repetitions. Two trials on each upper limb were undertaken, alternating
between the non-operated and operated limbs, with the first trial always undertaken on
the non-operated side. During each maximal effort, patients were asked to perform to
their maximal muscle strength, while verbal encouragement was provided, standardized
96
across all patients and trials. Patients were given adequate rest in between trials to
minimize fatigue, though this was not standardized and based upon the patient’s
individual readiness to proceed. For all trials, the peak torque (Nm), time to peak torque
(secs) and total work (J) performed over the range of motion were obtained, and data were
recorded as absolute values.
Figure 1. A patient performing humeral (A) internal and (B) external rotation on the
Biodex Isokinetic Dynamometer.
97
Radiological Evaluation
Radiographic analysis was performed with MRI at 16 weeks post-surgery. All scans
utilized a 1.5T unit (Sonata Maestro Class; Siemens, Erlangen, Germany) with 40mT/m
gradient power. Multiple images were obtained in oblique coronal, oblique sagittal and
axial planes with both short-tau inversion recovery (STIR) and turbo spin echo (TSE) T1-
weighted sequence. MRI assessment was performed by an experienced radiologist, who
did not perform the PRP injections as part of the primary RCT and was therefore blinded
to patient group allocation. MR images were graded as per the Sugaya classification
(Sugaya, et al., 2007): Grade 1 = no tear; Grade 2 = sufficient tendon thickness but with
high signal change; Grade 3 = insufficient thickness but no tendon discontinuity; Grade
4 = small full-thickness re-tear; Grade 5 = large full-thickness re-tear.
Statistical Analysis
Firstly, statistical procedures were performed with both groups as part of the primary
RCT (PRP and control) pooled together (n=60). Independent sample t-tests were initially
employed to determine if partial thickness tendon re-tears led to poorer strength and
functional scores, compared to an intact repair. Participants were grouped according to
their 16-week post-operative MRI Sugaya grading (Grade 1, 2 or 3), while those with
Grade 4 or 5 were omitted from the analysis (n=2). Group means (SD) for the Sugaya
grading classifications were presented.
A series of discriminant analyses were employed to determine if the Sugaya grading
(presence and severity of a tear) could be predicted using PRO measures and/or strength
data. Linear combinations of predictor variables were formed to serve as the basis for
98
classifying cases into two groups: a partial re-tear group (Sugaya Grades 2 and 3) and an
intact repair group (Sugaya Grade 1). When using discriminant analysis, it is
recommended that the number of variables should be used so that there are data for at
least three subjects per variable, and the number of variables should not exceed the
number of subjects in the smallest group (Carter & Ackland, 1998; Tatsuoka, 1971).
These requirements were satisfied in our analysis. The discriminant analysis used the
method of Wilks’ lambda and a stepwise forward inclusion model. Analyses were
evaluated in terms of a high eigenvalue, high canonical correlation squared, low and
significant Wilks’ lambda (p<0.001), and a high percentage of correctly classified
subjects, as suggested by Carter and Ackland (1998), and successful classification would
be above 80%. We began the analysis with the variable that had the highest prediction
(QuickDASH), and then added variables to a maximum of five. Statistical analysis was
performed using SPSS software (SPSS, Version 22.0, SPSS Inc., USA), while statistical
significance was determined at P < 0.05.
RESULTS
Group means (SD) are presented for patients classified by Sugaya Grades 1 (n=21, 35%),
2 (n=23, 38%) or 3 (n=14, 23%), and these groups were compared at 16 weeks post-
surgery (Table 2). One patient did not tolerate the post-operative MRI scan due to
claustrophobia, instead undergoing an US performed by an experienced musculoskeletal
radiologist. This tendon repair was intact, with no evidence of thinning or discontinuity,
so for the purpose of this study it was included in the Grade 1 Sugaya classification. No
significant differences (p>0.05) in PRO or isokinetic strength measures were observed
between these three groups based on the Sugaya tear classification system, at 16 weeks
post-surgery.
99
Table 2. Mean (SD) scores for the patient-reported outcome (PRO) and isokinetic
maximal strength measures (at an angular velocity of 60°/s) employed, for patients with
intact (Grade 1) and partial (Grade 2 and 3) supraspinatus tendon re-tears. Independent
sample t-test comparisons are provided between groups (p values).
Variable
Sugaya Classification
Group Comparison
Grade
1
(n=21)
Grade
2
(n=23)
Grade
3
(n=14)
Grade 1 v 2
Grade 1 v 3
Grade 2 v 3
OSS 38.9
(6.4)
39.2
(5.1)
40.7
(8.0)
-0.191
(.849)
-0.723
(.475)
-0.645
(.524)
VAS 1.5
(1.4)
1.3
(1.3)
1.5
(2.0)
0.485
(.631)
0.115
(.909)
-0.235
(.815)
QuickDASH 21.9
(12.4) 17.5
(11.9) 18.3
(17.8)
1.137 (.263)
0.687 (.497)
-0.149 (.882)
SF-12 (PCS) 42.1 (8.1)
42.7 (5.8)
44.0 (9.3)
-
0.240
(.812)
-0.618 (.541)
-0.514 (.611)
SF-12 (MCS) 53.7
(11.6)
55.3
(7.7)
54.9
(9.6)
-
0.508 (.615)
-0.322
(.749)
0.109
(.914)
Arm Flexion Peak Torque
(Nm)
77.1
(22.6)
76.5
(15.4)
74.9
(18.9)
0.099
(.922)
0.297
(.768)
0.282
(.780)
Arm Flexion Total Work (J) 61.7
(26.5)
63.2
(21.3)
62.0
(26.2)
-
0.213 (.832)
-0.036
(.971)
0.153
(.879)
External Humeral Rotation
Peak Torque (Nm)
75.8
(21.2)
71.1
(16.8)
82.4
(21.8)
0.820
(.417)
-0.896
(.377)
-1.777
(.084)
External Humeral Rotation
Total Work (J)
68.2
(49.5)
53.7
(22.7)
66.2
(26.0)
1.266
(.212)
0.135
(.893)
-1.543
(.132)
OSS = Oxford Shoulder Score; VAS = Visual Analogue Pain Scale for pain; QuickDASH = Quick
Disability of the Arm, Shoulder and Hand; SF-12 = 12-item Short Form Health survey; PCS = Physical
Component Subscale; MCS = Mental Component Subscale.
Descriptive statistics for the intact (Grade 1) and partial re-tear (Grade 2 and 3 pooled)
groups are shown in Table 3. At 16 weeks post surgery, mean scores for strength and
function for the intact repair group compared to the partial re-tear group were not
100
significant. Discriminant analysis results in Table 4 revealed the QuickDASH alone
produced a 97% true positive rate for predicting partial re-tears, but also a 90% false
positive rate. The ability to discriminate between groups was enhanced with up to five
variables entered; however, only 87% of the partial re-tear group, and 36% of the intact
repair group were correctly classified.
Table 3. Descriptive statistics (mean ± SD) for patients with intact repairs (Grade 1) and
partial (Grade 2 and 3 pooled) supraspinatus tendon re-tears.
Variable Intact repair
Group (n=21)
Partial re-tear
Group (n=37) Total
OSS 38.9 ± 6.4 40.1 ± 6.3 39.6 ± 6.3
VAS 1.5 ± 1.4 1.4 ± 1.6 1.4 ± 1.5
QuickDASH 20.9 ± 12.4 18.1 ± 14.6 19.2 ± 13.7
External Humeral Rotation
Peak Torque (Nm) 76.9 ± 20.6 75.0 ± 19.9 75.7 ± 20.0
Arm Flexion Peak Torque
(Nm) 77.3 ± 22.0 76.0 ± 17.0 76.5 ± 18.9
Time to Peak Torque for
External Humeral Rotation
(s)
0.54 ± 0.45 0.60 ± 0.42 0.58 ± 0.43
OSS = Oxford Shoulder Score; VAS = Visual Analogue Pain Scale for pain; QuickDASH = Quick
Disability of the Arm, Shoulder and Hand.
101
Table 4. Discriminant analysis for variables predicting an intact repair (n=21, Grade 1 Sugaya Classification) or partial re-tears (n=37, Grade 2 and 3
Sugaya Classification).
Prediction variables entered 2
Statistic 1
Number Classified (%)
Actual Group Membership
Predicted Group Membership
EV CC WL Sig Intact repair Partial re-tear
A. QuickDASH 0.011 0.104 0.989 0.465 Intact repair 2 (10%) 19 (90%)
Partial re-tear 1 (3%) 30 (97%)
B. QuickDASH, ER Pk Tq 0.034 1.82 0.967 0.429 Intact repair 4 (18%) 18 (82%)
Partial re-tear 3 (10%) 28 (90%)
C. QuickDASH, ER Pk Tq, OSS 0.039 0.194 0.962 0.594 Intact repair 5 (23%) 17 (77%)
Partial re-tear 4 (13%) 27 (87%)
D. QuickDASH, ER Pk Tq, OSS, TPT ER 0.045 0.207 0.957 0.717 Intact repair 7 (32%) 15 (68%)
Partial re-tear 4 (13%) 26 (87%)
E. QuickDASH, ER Pk Tq, OSS, TPT ER, AF Pk Tq 0.045 0.207 0.957 0.837 Intact repair 8 (36%) 14 (64%)
Partial re-tear 4 (13%) 26 (87%)
1 EV = eigenvalue, CC = canonical correlation, WL = Wilks’ lambda, Sig = prediction significance of the discriminant function.
2 ER Pk Tq = Peak torque for humeral external rotation at 60⁰ /s; AF Pk Tq = Peak torque for arm flexion at 60⁰ /s; TPT ER = time to peak torque in humeral external rotation.
102
DISCUSSION
The use of post-operative MRI and/or US to evaluate the outcome of rotator cuff surgery
can be costly and time consuming. Several researchers have attempted to determine
whether the healing progress of a conservatively treated rotator cuff tendon tear can be
predicted using common, clinical shoulder assessments, with little success (Ainsworth &
Lewis, 2007; Hughes, et al., 2008; Murrell & Walton, 2001). This study aimed to: a)
investigate if differences in common shoulder PRO measures and isokinetic strength tests
could be observed between patients with intact or partial re-tears, classified by MRI, at
16 weeks after rotator cuff repair surgery, and; (b) determine if early post-surgical tendon
healing could be predicted using these PRO measures and strength tests alone, without
the need for radiological assessment.
This study found no significant difference in the employed shoulder PRO measures, nor
isokinetic strength evaluation, between patient groups stratified by the Sugaya MRI
classification system (Grades 1, 2 or 3) for rotator cuff tears at 16 weeks post-surgery.
Studies have investigated the diagnostic accuracy of clinical tests for rotator cuff
pathology (Hegedus, et al., 2008; Hegedus, et al., 2012; Hughes, et al., 2008), and
concluded that most tests are inaccurate and cannot be recommended for clinical
diagnosis alone. This may well be the case post-operatively, and more robust testing in
this area is required. When employing radiology to investigate rotator cuff pathology, it
has been reported in a number of studies that both US and MRI are accurate in the
detection of rotator cuff lesions (Kluger, et al., 2003; Teefey, et al., 2004). Codsi, et al.
(2014) suggested US was comparable to MRI when evaluating rotator cuff integrity, and
that post-surgical US results should be compared with MRI results for a period of time
before relying solely on US for diagnosis. However, Ardic, et al. (2006) reported MRI
103
to be superior to US, while Goldberg, et al. (2003) reported that US was not a reliable
tool for diagnosing full thickness rotator cuff tears. Sonnabend, et al. (1997) reported on
the accuracy of US in diagnosing full thickness rotator cuff tears and as a “useful adjunct”
in the diagnosis of partial tears; however, they also noted it was operator-dependent. For
these reasons, we chose to use MRI for confirmation of tendon healing.
The discriminant analysis showed the QuickDASH alone produced a 97% true positive
rate for predicting partial re-tears, but also a 90% false positive rate, revealing the test to
be sensitive but not specific. The addition of other shoulder PRO measures or isokinetic
strength evaluations did not greatly improve the predictive capability of the patient’s early
tendon repair outcome, and so we must conclude that combining such measures does not
give confidence in the diagnosis of partial re-tears. At this stage, we must conclude that
some form of radiological assessment (MRI or US) be used for this purpose. However,
it should also be noted that the concurrent use of shoulder-specific PRO measures and/or
strength evaluation remain important in guiding the rehabilitation process after rotator
cuff repair, as well as the patient’s specific return to work or sport. Furthermore, while
Nho, et al. (2009) reported that 100% of re-tears occurred in the first three months post-
surgery, Kluger, et al. (2009) reported that most early post-operative re-tears appear to be
a failure to heal, and that repair site integrity at six months was a predictor of 7-year
clinical outcome. Therefore, based on our results and pre-existing literature, if a patient
has a QuickDASH score that is greater (i.e. worse) than the mean value we report at 16
weeks post-surgery, then it may be likely they have incomplete healing or partial re-
tearing of the tendon. This would then warrant adjunct radiological assessment. While
these results suggest that PRO measures and shoulder strength in a patient with a
completely intact repair is equivalent to that of a partial re-tear, at least at 16 weeks post-
surgery, the natural history in ongoing high demand work or sport is for partial tears to
104
deteriorate. Therefore, subsequent imaging in these patients may allow for a decelerated
rehabilitation program or vocational counselling on restricted work duties and prognosis.
This study has some acknowledged inherent limitations. Firstly, the patient follow-up
was limited to 16 weeks. Research by Sonnabend, et al. (1997) has previously
demonstrated that a significant portion of Sharpey fibres have reconstituted and matured
at the tendon repair site by 3-4 months. Furthermore, accurate classification of rotator
cuff tendon healing has been suggested to be importance at this time as it affects the
rehabilitation strategy, especially for patients who intend to return to employment in
physical work or to physically demanding sports. However, if MRI evaluations were to
be repeated at a later time (such as 12 months) it is possible that more structural tearing
may be observed, contributing to more pain and diminished function. While the primary
aim of this study was to assess early post-operative tendon healing, future research may
include a longer-term follow-up.
A second limitation may result from the primary RCT, whereby half of this patient cohort
received two PRP injections post-surgery. However, as reported previously there were
no differences observed between the PRP and control groups at 16 weeks post surgery in
any of the assessments employed, including the shoulder-specific PRO measures,
shoulder range of motion, isokinetic strength evaluation and MRI-based assessment
(Wang, et al., 2015). This result created the opportunity to combine the original groups
(PRP or control) into one cohort for this analysis.
Thirdly, we employed PRO instruments used routinely through our clinical practice and
research, and we appreciate other shoulder-specific scores are available. It is possible
that differences (or an improved predictive capacity) may be observed in other clinical
105
and functional shoulder evaluations. Fourthly, strength tests also have some inherent
limitations as they are unable to differentiate between true muscular weakness and pain-
related weakness (Bigoni, et al., 2009). The results of the isokinetic strength tests also
rely upon a maximal effort being made by the patient. While clear, standardized
instructions and verbal encouragement were provided to all participants, it must be
acknowledged that this was the first time many of the patients would have maximally
stressed their operated limb since surgery, and some may have been hesitant to exert
maximal effort. Protocols for future research may require a familiarisation session prior
to the testing session. Furthermore, Bigoni, et al. (2009) has previously reported that
isokinetic strength testing is a powerful tool for evaluating strength following rotator cuff
surgery, so it may be that alternate testing protocols, incorporating shoulder abduction,
may more accurately discriminate between groups.
CONCLUSION
This study found no significant difference in the employed shoulder PRO measures, nor
isokinetic strength evaluation, between patient groups stratified by the Sugaya MRI
classification system for rotator cuff tears at 16 weeks post-surgery. Furthermore, the
presence of an intact repair or partial re-tear after rotator cuff surgery could not be
accurately predicted by these clinical and functional shoulder evaluations. Our results
suggest that correct classification of tendon healing in the early stage following rotator
cuff surgery must involve medical imaging. This will give confidence in patient
management of appropriate return-to-work and/or sport rehabilitation programs.
Reliance on PRO measures and/or functional scores alone to make an accurate assessment
is not supported by our data.
106
REFERENCES
Ainsworth, R., & Lewis, J. (2007). Exercise therapy for the conservative management of
full thickness tears of the rotator cuff: a systematic review. Br J Sports Med, 41,
200-210.
Ardic, F., Kahraman, Y., Kacar, M., Kahraman, M. C., Findikoglu, G., & Yorgancioglu,
Z. R. (2006). Shoulder impingement syndrome: relationships between clinical,
functional, and radiologic findings. Am J Phys Med Rehabil, 85(1), 53-60.
Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing
influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the
Journal of Arthroscopic and Related Surgery, 27(8), 1029-1035.
Beaton, D. E., Wright, J. G., Katz, J. N., & Upper Extremity Collaborative, G. (2005).
Development of the QuickDASH: comparison of three item-reduction
approaches. J Bone Joint Surg Am, 87(5), 1038-1046.
Bigoni, M., Gorla, M., Guerrasio, S., Brignoli, A., Cossio, A., Grillo, P., et al. (2009).
Shoulder evaluation with isokinetic strength testing after arthroscopic rotator cuff
repairs. Journal of Shoulder and Elbow Surgery, 18, 178.
Boileau, P., Brassart, N., Watkinson, D. J., Carles, M., Hatzidakis, A. M., & Krishnan, S.
G. (2005). Arthroscopic repair of full-thickness tears of the supraspinatus: does
the tendon really heal? Journal of Bone and Joint Surgery (Am), 87(6), 1229-
1240.
Carter, J. E., & Ackland, T. R. (1998). Sexual dimorphism in the physiques of World
Championship divers. J Sports Sci, 16(4), 317-329.
Charousset, C., Bellaiche, L., Kalra, K., & Petrover, D. (2010). Arthroscopic repair of
full-thickness rotator cuff tears: is there tendon healing in patients aged 65 years
or older? Arthroscopy, 26(3), 302-309.
107
Cheung, E. V., Silverio, L., & Sperling, J. W. (2010). strategies of biologic augmentation
of rotator cuff repair: a review. Clin Orthop Relat Res, 468(6), 1476-1884.
Cho, N. S., & Rhee, Y. G. (2009). The factors affecting the clinical outcome and integrity
of arthroscopically repaired rotator cuff tears of the shoulder. Clin Orthop Surg,
1(2), 96-104.
Cho, N. S., Yi, J. W., Lee, B. G., & Rhee, Y. G. (2010). Retear patterns after arthroscopic
rotator cuff repair: single-row versus suture bridge technique. Am J Sports Med,
38(4), 664-671.
Codsi, M. J., Rodeo, S. A., Scalise, J. J., Moorehead, T. M., & Ma, C. B. (2014).
Assessment of rotator cuff repair integrity using ultrasound and magnetic
resonance imaging in a multicenter study. J Shoulder Elbow Surg, 23(10), 1468-
1472.
Dawson, J., Fitzpatrick, R., & Carr, A. (1996). Questionnaire on the perceptions of
patients about shoulder surgery. J Bone Joint Surg Br, 78(4), 593-600.
Dawson, J., Hill, G., Fitzpatrick, R., & Carr, A. (2001). The benefits of using patient-
based methods of assessment. Medium-term results of an observational study of
shoulder surgery. J Bone Joint Surg Br, 83(6), 877-882.
Galatz, L. M., Ball, C. M., Teefey, S. A., Middleton, W. D., & Yamaguchi, K. (2004).
The outcome and repair of completely arthroscopically repaired large and massive
rotator cuff tears. Journal of Bone and Joint Surgery (Am), 86(2), 219-224.
Goldberg, J. A., Bruce, W. J., Walsh, W., & Sonnabend, D. H. (2003). Role of community
diagnostic ultrasound examination in the diagnosis of full-thickness rotator cuff
tears. ANZ J Surg, 73(10), 797-799.
Gulotta, L. V., & Rodeo, S. A. (2009). Growth factors for rotator cuff repair. Clinical
Sports Medicine, 28, 13-23.
108
Gummesson, C., Ward, M. M., & Atroshi, I. (2006). The shortened disabilities of the arm,
shoulder and hand questionnaire (QuickDASH): validity and reliability based on
responses within the full-length DASH. BMC Musculoskelet Disord, 7, 44.
Harryman, D. T., 2nd, Mack, L. A., Wang, K. Y., Jackins, S. E., Richardson, M. L., &
Matsen, F. A., 3rd. (1991). Repairs of the rotator cuff. Correlation of functional
results with integrity of the cuff. J Bone Joint Surg Am, 73(7), 982-989.
Hegedus, E. J., Goode, A., Campbell, S., Morin, A., Tamaddoni, M., Moorman, C. T.,
3rd, et al. (2008). Physical examination tests of the shoulder: a systematic review
with meta-analysis of individual tests. Br J Sports Med, 42(2), 80-92; discussion
92.
Hegedus, E. J., Goode, A. P., Cook, C. E., Michener, L., Myer, C. A., Myer, D. M., et al.
(2012). Which physical examination tests provide clinicians with the most value
when examining the shoulder? Update of a systematic review with meta-analysis
of individual tests. Br J Sports Med, 46(14), 964-978.
Hughes, P. C., Taylor, N. F., & Green, R. A. (2008). Most clinical tests cannot accurately
diagnose rotator cuff pathology: a systematic review. Aust J Physiother, 54(3),
159-170.
Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term
survivorship of rotator cuff repairs using ultrasound and magnetic resonance
imaging analysis. Am J Sports Med, 39(10), 2071-2081.
Kluger, R., Mayrhofer, R., Kroner, A., Pabinger, C., Partan, G., Hruby, W., et al. (2003).
Sonographic versus magnetic resonance arthrographic evaluation of full-
thickness rotator cuff tears in millimeters. J Shoulder Elbow Surg, 12(2), 110-116.
Murrell, G. A., & Walton, J. R. (2001). Diagnosis of rotator cuff tears. Lancet, 357(9258),
769-770.
109
Nho, S. J., Shindle, M. K., Adler, R. S., Warren, R. F., Altchek, D. W., & MacGillivray,
J. D. (2009). Prospective analysis of arthroscopic rotator cuff repair: subgroup
analysis. J Shoulder Elbow Surg, 18(5), 697-704.
Oh, J. H., Kim, S. H., Kang, J. Y., Oh, C. H., & Gong, H. S. (2010). Effect of age on
functional and structural outcome after rotator cuff repair. Am J Sports Med,
38(4), 672-678.
Olley, L. M., & Carr, A. J. (2008). The use of a patient-based questionnaire (the Oxford
Shoulder Score) to assess outcome after rotator cuff repair. Ann R Coll Surg Engl,
90, 326-331.
Park, M. C., Elattrache, N. S., Ahmad, C. S., & Tibone, J. E. (2006). "Transosseous-
equivalent" rotator cuff repair technique. Arthroscopy, 22(12), 1360 e1361-1365.
Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-
594.
Sonnabend, D. H., Hughes, J. S., Giuffre, B. M., & Farrell, R. (1997). The clinical role
of shoulder ultrasound. Aust N Z J Surg, 67(9), 630-633.
Sugaya, H., Maeda, K., Matsuki, K., & Moriishi, J. (2007). Repair integrity and functional
outcome after arthroscopic double-row rotator cuff repair. A prospective outcome
study. J Bone Joint Surg Am, 89(5), 953-960.
Tashjian, R. Z., Deloach, J., Porucznik, C. A., & Powell, A. P. (2009). Minimal clinically
important differences (MCID) and patient acceptable symptomatic state (PASS)
for visual analog scales (VAS) measuring pain in patients treated for rotator cuff
disease. J Shoulder Elbow Surg, 18(6), 927-932.
Tatsuoka, M. M. (1971). Multivariate analysis; techniques for educational and
psychological research. New York,: Wiley.
110
Teefey, S. A., Rubin, D. A., Middleton, W. D., Hildebolt, C. F., Leibold, R. A., &
Yamaguchi, K. (2004). Detection and quantification of rotator cuff tears.
Comparison of ultrasonographic, magnetic resonance imaging, and arthroscopic
findings in seventy-one consecutive cases. J Bone Joint Surg Am, 86-A(4), 708-
716.
Wang, A., McCann, P., Colliver, J., Koh, E., Ackland, T., Joss, B., et al. (2015). Do
Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing
and Functional Recovery After Arthroscopic Supraspinatus Repair? A
Randomized Controlled Trial. Am J Sports Med (in press).
Ware, J., Jr., Kosinski, M., & Keller, S. D. (1996). A 12-Item Short-Form Health Survey:
construction of scales and preliminary tests of reliability and validity. Med Care,
34(3), 220-233.
111
CHAPTER 5
SUMMARY, CONCLUSIONS AND RECOMMENDATIONS
The main purpose of this thesis was to investigate the effect of PRP injections following
rotator cuff repair surgery on early tendon healing and functional recovery. Current
research in the area of PRP augmentation following rotator cuff repair surgery remains
controversial. This is complicated by a lack of standardisation of PRP products,
differences in timing of delivery protocols, and optimal platelet concentrations. The
research investigated if delayed and repeated PRP injections would accelerate the early
structural healing following surgical repair of supraspinatus tendon as well as improving
patient function and strength (see Paper 1 in Chapter 3). In addition, the research also
aimed to determine if early post-surgery tendon healing could be predicted independently
of an MRI scan, using a combination of patient-reported functional and quality of life
questionnaires and isokinetic strength data (see Paper 2 in Chapter 4).
In Paper 1 a prospective, randomised controlled study design was used to investigate
radiological and functional assessment up to and including 16 weeks post rotator cuff
repair surgery in 60 patients (30 treatment, 30 control group). Patients randomly assigned
to the treatment group received two PRP injections under guided-US (at 7 and 14 days
post-surgery), while the control group received no placebo injection. MRI was used to
assess the structural tendon healing at 4 months, with rotator cuff appearances graded
according to the Sugaya classification. Functional assessment was undertaken pre-
surgery, and at 6, 12 and 16 weeks post-surgery. These included the OSS, QuickDASH,
VAS and SF-12 inventories. Isokinetic strength and ROM were also measured at 16
weeks post-surgery.
112
No significant difference was observed in structural healing of the tendon at 16 weeks
between the treatment and control groups, a finding that did not support our first
hypothesis. Functional outcome scores improved in all patients following surgery - at 12
and 16 weeks the OSS, VAS and SF-12 improved significantly from pre-surgery.
However, no significant difference was observed in the functional scores between the
treatment and control groups at any of the post-surgery time points. In addition, no
significant difference was observed for strength or ROM between the groups at 16 weeks.
This finding did not support the second hypothesis of Paper 1, that PRP would improve
early function and strength compared to the control group.
Participants from Paper 1 were able to be pooled for analysis in Paper 2 since no
significant differences were observed between the treatment and control groups in MRI
classification, patient reported functional scores and isokinetic strength (Wang et al.,
2015). Paper 2 aimed to determine if it were possible to predict the success of the tendon
repair at 16 weeks post-surgery without the costly and time-consuming requirement of
MRI. Previous research had shown that Sharpey fibres begin to reconstitute at 3 months,
with maturation seen at 4 months. Furthermore, it was reported that the majority of
recurrent tears occurred in the first 3-4 months (Kluger, et al., 2011; Miller, et al., 2011;
Nho, et al., 2009); highlighting this early tendon healing phase as being critical for long-
term success. Prediction of tendon healing at this early stage using low cost strength and
functional outcomes could prove useful, as this could influence early post-surgical
management as well as the patient’s individual return to work and/or sport strategy. Paper
2 sought to determine if differences in patient shoulder function and strength could be
detected for those patients with partial tendon re-tears compared to those with intact
repairs 16 weeks post surgery, regardless of their initial PRP group allocation. The second
aim of Paper 2 was to determine if patients with partial re-tears and incomplete healing
113
could be predicted based on function and strength alone, without the need for early post-
surgery imaging.
No significant differences were observed in patient shoulder function or isokinetic
strength at 16 weeks post rotator cuff repair between those with an intact repair and those
with a partial tendon re-tear; this finding did not support the first hypothesis of Paper 2.
Discriminant analysis showed that while the QuickDASH produced a 97% true positive
rate for predicting partial re-tears, it also produced a 90% false positive rate. With the
addition of up to five variables entered, the ability to discriminate between intact repairs
and partial re-tears was enhanced; only 87% of the partial re-tear group and 36% of the
intact repair group were correctly classified, thus not supporting the second hypothesis.
The results of this study suggest that correct classification of early tendon healing
following rotator cuff repair surgery must involve medical imaging.
A number of limitations should be acknowledged within these studies. Firstly, the patient
follow-up period was limited to 16 weeks. Research has previously demonstrated that a
significant proportion of Sharpey fibres have reconstituted and matured at the tendon-
repair site by 3-4 months (Sonnabend, et al., 2010). Also, accurate classification of
rotator cuff tendon healing has been suggested to be important at 16 weeks, as it affects
the rehabilitation strategy, especially for those returning to physically demanding
employment or sports. However, we acknowledge that should MRI evaluations be
repeated at a later time, more structural tearing may be observed, which would contribute
to more pain and decreased function. While this study focused on the early assessment
of tendon healing, future research should include a longer follow-up period.
114
Patients were not blinded as to their grouping in Paper 1, as it was considered impractical
to having patients complete two placebo injections. Patient knowledge of their
intervention group may cause a positive bias among members of the PRP group, however,
both groups were equivalent in terms of the study outcomes. An independent,
experienced radiologist who was blinded to the participants’ group allocation, and who
was not involved in the PRP injections, performed all MRI evaluations.
The PRP product used in Paper 1 does not achieve the high concentration of platelets that
some other commercially available PRP products report. However, it has been suggested
that markedly elevated supra physiological levels of platelets and growth factors may not
be of benefit, and could in fact be detrimental to tendon healing (Barber, et al., 2011;
Sundman, et al., 2011). Optimal tendon healing requires the appropriate concentration of
growth factors, as well as appropriate timing of delivery in the tendon-healing cascade in
order to be maximally effective. This highlights the need for a standardised protocol to
be developed for future research.
The functional scores used in both papers are used routinely in clinical practice and
research, however, we appreciate there are other shoulder-specific scores available, and
it is possible that differences, or an improved prediction capacity, may be observed with
other clinical shoulder evaluations. Strength tests also have some inherent limitations, as
they are unable to differentiate between true muscular weakness and pain-related
weakness (Bigoni, et al., 2009). The results of the isokinetic strength tests also rely on a
maximal effort being made by the patient. Whilst clear, standardised instructions and
verbal encouragement was provided, it is acknowledged that some patients may have
been hesitant to exert maximal strength. The tests undertaken at 16 weeks post-surgery
were the first time most patients would have maximally exerted their shoulder since their
115
operation. Future research protocols might require a familiarisation session prior to the
testing session. Furthermore, isokinetic strength testing has been reported to be a
powerful tool for evaluating strength following rotator cuff surgery (Bigoni, et al., 2009),
so it may be that alternate testing protocols, incorporating shoulder abduction could be
considered in future research. We did not include shoulder abduction in our protocol as
it was considered too early post-surgery to directly stress the repaired tendon.
A perceived limitation of Paper 2 may result from the primary RCT (Paper 1), where half
of the cohort received two PRP injections post-surgery. However, as previously
reported, there were no observed differences in any of the outcome measures between the
PRP and control groups at 16 weeks post-surgery (Wang, et al., 2015). This result created
the opportunity for us to combine the original groups into one cohort for this analysis.
This is the first study to our knowledge that evaluated the efficacy of a post-surgical PRP
delivery protocol to improve tendon healing and functional outcomes following rotator
cuff repair. While this research reiterated that PRP injections post rotator cuff surgery
are safe, we concluded that PRP does not accelerate early tendon healing nor improve
functional or strength outcomes. Future research might include randomised controlled
trials of other commercially available PRP products with alternative delivery vehicles and
dosing regimes, and with longer post-surgery follow-up.
116
REFERENCES
Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing
influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the
Journal of Arthroscopic and Related Surgery, 27(8), 1029-1035.
Bigoni, M., Gorla, M., Guerrasio, S., Brignoli, A., Cossio, A., Grillo, P., et al. (2009).
Shoulder evaluation with isokinetic strength testing after arthroscopic rotator cuff
repairs. Journal of Shoulder and Elbow Surgery, 18, 178.
Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term
survivorship of rotator cuff repairs using ultrasound and magnetic resonance
imaging analysis. Am J Sports Med, 39(10), 2071-2081.
Miller, B. S., Downie, B. K., Kohen, R. B., Kijek, T., Lesniak, B., Jacobson, J. A., et al.
(2011). When do rotator cuff repairs fail? Serial ultrasound examination after
arthroscopic repair of large and massive rotator cuff tears. Am J Sports Med,
39(10), 2064-2070.
Nho, S. J., Shindle, M. K., Adler, R. S., Warren, R. F., Altchek, D. W., & MacGillivray,
J. D. (2009). Prospective analysis of arthroscopic rotator cuff repair: subgroup
analysis. J Shoulder Elbow Surg, 18(5), 697-704.
Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-
594.
Sundman, E. A., Cole, B. J., & Fortier, L. A. (2011). Growth factor and catabolic cytokine
concentrations are influenced by the cellular composition of platelet-rich plasma.
Am J Sports Med, 39(10), 2135-2140.
117
Wang, A., McCann, P., Colliver, J., Koh, E., Ackland, T., Joss, B., et al. (2015). Do
Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing
and Functional Recovery After Arthroscopic Supraspinatus Repair? A
Randomized Controlled Trial. Am J Sports Med (in press).
Ref 20290046
15 June 2011
Miss J Colliver132 A York StSubiaco WA 6008
Dear Miss Colliver
RESEARCH PROPOSAL - MASTER OF SCIENCE - RESEARCH
I am pleased to inform you that the Board of the Graduate Research School has considered your Research Proposal and, it is accepted without the requirement for changes or clarification.
In addition your research proposal is accepted subject to:Please note that approval is required from the appropriate UWA committee notwithstanding that the project might have been approved by an external agency (e.g hospital) or another university.
Your proposal indicates that approval from UWA Human Research Ethics Committee, iscurrently being sought in relation to your research. Until you provide us with notification that you have approval, or otherwise, from the UWA Human Research Ethics Committee, the status of your research proposal will be marked as provisory.
The supervisors for your research are recorded as being -Coordinating supervisor: Winthrop Professor T Ackland (40%)Co supervisor: Prof A Wang (40%)Co supervisor: Adj/A/Prof B Joss (20%)
On behalf of the Board please accept my best wishes for the remainder of your candidature.
Yours sincerely
Barbara TelferAdministrative Officer, Candidature
cc Professor A Gordon (Graduate Research Coordinator)Winthrop Professor T Ackland
SCHOOL OF SPORT SCIENCE, EXERCISE AND HEALTH
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Dear Professor Ackland
HUMAN RESEARCH ETHICS OFFICE – RECOGNITION OF ETHICS APPROVAL FROM ANOTHER HUMAN RESEARCH ETHICS COMMITTEE
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Our Ref: RA/4/1/4872 24 June 2011
Project: Does autologous conditioned plasma enhance rotator cuff healing after surgery?
Thank you for your correspondence enclosing the necessary documents to facilitate recognition of the ethics approval for the above project granted by an external Human Research Ethics Committee (HREC) registered with the National Health and Medical Research Council (NHMRC).
It is noted that you have ethics approval from South Metropolitan, approval number 11/75.
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Student(s): Jessica Anne Colliver
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Name Faculty / School RoleWinthrop Professor Timothy Robert Ackland Sport Science, Exercise & Health (School of) Chief Investigator
Clinical Associate Professor Allan Wenli Wang Sport Science, Exercise & Health (School of) Co-Inv
Dr Brendan Keith Joss Sport Science, Exercise & Health (School of) Co-Inv
Information Sheet
Does autologous conditioned plasma enhance rotator cuff healing after surgery?
TO BE USED IN CONJUNCTION WITH THE CONSENT FORM
Chief Investigator Dr Allan Wang, Consultant Orthopaedic Surgeon
and Clinical Professor, UWA [email protected] Co Investigators Dr Eamon Koh, Consultant Radiologist, Fremantle Hospital Ms Jessica Colliver, Exercise Physiologist and Study Coordinator
Prof Timothy Ackland, Winthrop Professor, UWA Dr Brendan Joss, Clinic Director, HFRC Prof Ming Hao Zheng, Winthrop Professor, UWA
We invite you to participate in this research study, supported by Arthrex Medical Company, concerning patients who have undergone surgery for a rotator cuff tear, and comparing the efficacy of post-surgery injections of autologous conditioned plasma (ACP) versus usual care. This study has been approved by the Human Research Ethics Committees of the South Metropolitan Area Health Service and the University of Western Australia. If you decide to take part in this study, it is important that you understand the purpose of the study and the procedures you will be asked to undergo. Please read the following pages, which will provide you with information about the treatments involved and the potential benefits, discomforts and precautions of the study. If you are currently involved in a research study you will be ineligible to participate in this one. What is the purpose of this research? Your family doctor has referred you for treatment of a rotator cuff tendon tear in your shoulder, which requires surgical repair. Unfortunately, surgical repair is sometimes unsuccessful, due to retraction of the torn tendon or poor tissue quality and occasionally following surgery the tendon may fail to heal well, or re-tear and further surgery is sometimes required. To combat these problems your surgeon has been investigating other options. There is increasing evidence that tendon healing is improved by ACP injection. Plasma is the component of blood with the red blood cells removed, and containing platelets and proteins which have been shown to improve tendon healing and function with Achilles tendon injuries, tennis elbow tendon damage and shoulder rotator cuff tendon tears1,2,3. The plasma is obtained by taking 10 ml of your own blood (“autologous plasma”) and spinning it in a centrifuge for 5 minutes just prior to injection.
School of Sport Science, Exercise and Health M408, The University of Western Australia 35 Stirling Highway Crawley, Western Australia 6009 Phone +61 8 6488 2361 Fax +61 8 6488 1039 Web www.sseh.uwa.edu.au CRICOS Provider Code: 00126G Parkway (Entrance No 3) Nedlands
The purpose of this research study is to investigate the benefit of autologous plasma injections for patients following rotator cuff tendon repair surgery. Duration of study If you choose to participate in this study you will be evaluated at regular intervals by Prof. Wang and the research team for 4 months after surgery. Clinical procedure Your shoulder will be evaluated with radiological studies including ultrasound or a MRI scan to assess the extent of rotator cuff damage. The standard surgical procedure to arthroscopically decompress then repair the rotator cuff tendon will be performed. After discharge from hospital you will be reviewed one week after surgery by Prof. Wang, who will then discuss this research study and if you agree to participate, we will enter you into the program. At this time, you will choose an envelope at random containing notification regarding which arm of the study you will enter (ie. the “treatment group” or the “control group”). The study coordinator, Miss Jess Colliver will then schedule you for post-operative care and assessment sessions. Patients assigned to the treatment group will be seen by Dr Eamon Koh, consultant radiologist at Fremantle Hospital. Patients in this group will have 10 ml (approximately two teaspoons) of their own blood taken, spun down, calcium chloride is added, and then 1-2 ml of this autologous conditioned plasma (ACP) is injected under ultrasound guidance into the rotator cuff repair site. Dr Koh will repeat this injection two weeks later. Regardless of whether you are an ACP treatment patient or control patient, your post- operative care and assessments will be identical. Pre- and post-surgery tests All patients who are referred to Prof. Wang for surgical treatment of a rotator cuff repair have a standard history, examination and radiology tests performed routinely. In addition, assessments of pain and function of the shoulder musculature will have been performed. If you agree to participate in this trial, we will use these data as your “pre-surgery” baseline scores. The post-surgical management is identical between Treatment and Control groups. Post-operative questionnaires are administered at 6, 12 and 16 weeks post-surgery (in Prof. Wang’s rooms). A routine post-operative MRI scan will be performed at 16 weeks to check the tendon repair site. Questionnaires administered to both groups include the Quick Disabilities of the Arm, Shoulder and Hand (QDASH), Oxford Shoulder Score (OSS), and Short Form-12 (SF-12). These questionnaires ask you to report on your shoulder pain, symptoms and how it affects your activities of daily living. At the time of the two injections we will also ask you for information regarding the levels of pain in your shoulder. Strength and range of motion testing post-surgery (at 16 weeks) is performed under the supervision of Miss Jessica Colliver who is an accredited Exercise Physiologist, at the UWA School of Sport Science, Exercise & Health in Crawley. The strength tests are performed within your level of tolerance to minimise any risk of injury or discomfort. Post-operative strength and ROM testing will only be performed once you have been cleared by Prof. Wang at the post-surgery clinical examination.
Testing time points: Measures Pre-op 6 weeks
post-op
12 weeks
post-op
16 weeks
post-op
MRI !
Strength !
ROM !
VAS (pain) ! ! ! !
QuickDASH ! ! ! !
OSS ! ! ! !
SF-12 ! ! ! !
What happens if I choose not to participate in this study? This will not affect your medical treatment from Prof. Wang. Your routine post-surgical rehabilitation and follow up will still go ahead as planned. What are the possible benefits for me to participate in this study? In both Treatment and Control groups, patients will receive a more in depth evaluation of the shoulder, before and after surgery by the research team, compared to patients not participating in this study. If you are allocated to the ACP treatment group, your outcome following surgery may or may not be better than the control group. This study will determine if there are significant positive benefits of ACP treatment. Previous studies of this type of injection have suggested less post-surgical pain4, earlier return to function3, and possibly lower rates of infection5. What are the possible side effects and risks of participating in this study? Autologous plasma injection to potentially enhance the outcome of tendon repair surgery is relatively new technology. Recent, similar studies have shown no adverse effects from platelet rich plasma injections3,4,5. However, there are general risks of surgery and anaesthesia for both participants and non-participants in this research study. There is a possible, minor increased risk from the ACP injection, including infection and pain after surgery. In the event of any complications in either the Treatment or Control group, all necessary medical care will be provided. Your participation in this study does not prejudice the right to compensation, which you may have under Statute or Common Law. The post-surgery MRI scans, which are performed to evaluate the healing of the rotator cuff tendon, may be claustrophobic for some patients. Will my personal information be kept confidential? Yes, your personal medical details will be kept private and confidential, and accessible only by the study Investigators. However, authorisation may be given to the hospital or Human Research Ethics Committee to verify the study procedures and conduct. The results of this research may be made available to other professionals at medical meetings or publications in medical journals. However, no personal identifying data will be used. By taking part in this study, you agree to not restrict the use of this de-identified data. Voluntary participation and withdrawal from the study Participation in this study is voluntary. If you choose not to participate, Prof. Wang will continue to provide the standard treatment for your shoulder condition. You may also withdraw from this study at any time, for whatever reason. Such withdrawal will not in any
way influence decisions regarding future standard or conventional medical treatment you may require. Further information If you have any questions about the study please contact the study coordinator, Ms Jessica Colliver on 0488 367 626, or by email to [email protected]. References: 1. Kon et al. Platelet Rich Plasma: A new clinical application: A pilot study for treatment of jumpers.
Knee Injury 2009 40: 598-603 2. Mishra & Pavelko Treatment of chronic elbow tendonosis with buffered platelet rich plasma. AJSM
2006 34: 1774-1778 3. Peerbooms et al. Positive effect of an autologous platelet concentrate in lateral epicondylitis in a
double blind randomised controlled trial. AJSM 2010 38: 255-263 4. Randelli et al. Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study.
Disability and Rehabilitation 2008 30(20): 1584 5. Randelli et al. Platelet rich plasma in arthroscopic rotator cuff repair. A prospective RCT JSES (in
press)
Approval to conduct this research has been provided by the South Metropolitan Area Health Service and The University of Western Australia, in accordance with their ethics review and approval procedures. Any person considering participation in this research project, or agreeing to participate, may raise any questions or issues with the researchers at any time. If you have any complaints or concerns about the way in which the study is being conducted, you may contact the Chairman of the South Metropolitan Area Health Service Human Research Ethics Committee on 9431 2929. Alternatively, you may contact the Human Research Ethics Office at The University of Western Australia on (08) 6488 3703 or by emailing to [email protected].
Prof. Allan Wang Principal Investigator
Ms Jessica Colliver AEP & Study Coordinator
Dr Eamon Koh Consultant Radiologist
Consent Form
Does autologous conditioned plasma enhance rotator cuff healing after surgery?
TO BE USED IN CONJUNCTION WITH THE INFORMATION SHEET
Participant’s Name:__________________________ Date of Birth:_________________ 1. I agree entirely voluntarily to take part in this study, supported by Arthrex Medical
Company. I am 18 years of age or over.
2. I have been given a full explanation of the purpose of this study, of the procedures involved and of what will be expected of me. The doctor has explained the possible problems that might arise as a result of my participation in this study.
3. I agree to inform the supervising doctor of any unexpected or unusual symptoms I
may experience. 4. I understand that I am entirely free to withdraw from the study at any time and that
this withdrawal will not in any way affect my future treatment or medical management. 5. I understand that the information in my medical records is essential to evaluate the
results of this study. I agree to the release of this information to the research staff and the clinical trial staff on the understanding that it will be treated confidentially.
6. I understand that I will not be referred to by name in any report concerning this study.
In turn, I cannot restrict in any way the use of the results that arise from this study. 7. I have been given and read a copy of this Consent Form and Information Sheet.
Participant Signature: _______________________________ Date _______________
Signature of Principal Investigator: _____________________ Date _______________
Approval to conduct this research has been provided by the South Metropolitan Area Health Service and The University of Western Australia, in accordance with their ethics review and approval procedures. Any person considering participation in this research project, or agreeing to participate, may raise any questions or issues with the researchers at any time. In addition, any person not satisfied with the response of researchers may raise ethics issues or concerns, and may make any complaints about this research project by contacting the Human Research Ethics Office at The University of Western Australia on (08) 6488 3703 or by emailing to [email protected]
School of Sport Science, Exercise and Health M408, The University of Western Australia 35 Stirling Highway Crawley, Western Australia 6009 Phone +61 8 6488 2361 Fax +61 8 6488 1039 Web www.sseh.uwa.edu.au CRICOS Provider Code: 00126G Parkway (Entrance No 3) Nedlands
Visual Analogue Scale (VAS)
Please rate how severe the pain in your affected shoulder has been (in the past 7 days) along the line below.
NAME: __________________ DATE: _________ Oxford Shoulder Score
Please circle the most appropriate answer of each of the following questions for your affected shoulder: 1. How would you describe the worst pain from your shoulder?
Unbearable Severe Moderate Mild None
2. How would you describe the pain you usually get from your shoulder?
Unbearable Severe Moderate Mild None
3. How much has the pain from your shoulder interfered with your work (including housework)?
Totally Greatly Moderately A little bit Not at all
4. Have you been troubled by pain in your shoulder in bed at night?
Every night Most nights Some nights Only 1 to 2 nights No nights
5. Have you had any trouble dressing yourself because of your shoulder?
Impossible to do Extreme difficulty Moderate difficulty
Very little difficulty
No difficulty at all
6. Have you had any trouble getting in and out of the car or using public transport because of your
shoulder? (Whichever one you tend to use)
Impossible to do Extreme difficulty Moderate difficulty
Very little difficulty
No difficulty at all
7. Have you been able to use a knife and fork at the same time?
No. Impossible With extreme difficulty
With moderate difficulty
With little difficulty
Yes, easily
8. Could you do the household shopping on your own?
No. Impossible With extreme difficulty
With moderate difficulty
With little difficulty
Yes, easily
9. Could you carry a tray containing a plate of food across the room?
No. Impossible With extreme difficulty
With moderate difficulty
With little difficulty
Yes, easily
10. Could you brush/comb your hair with the affected arm?
No. Impossible With extreme difficulty
With moderate difficulty
With little difficulty
Yes, easily
11. Could you hang your clothes up in a wardrobe with your affected arm?
No. Impossible With extreme difficulty
With moderate difficulty
With little difficulty
Yes, easily
12. Have you been able to wash and dry yourself under both arms?
No. Impossible With extreme difficulty
With moderate difficulty
With little difficulty
Yes, easily
NAME: __________________ DATE: ______
Quick DASH This questionnaire asks you about your symptoms as well as your ability to perform certain activities. Please answer every question, based on you condition in the past week, by circling the number of the appropriate answer. If you did not have the opportunity to perform a certain activity in the past week, please make your best estimate of which response would be most accurate. It doesn’t matter which arm you use to perform the activity; please answer based on your ability regardless of how you perform the task. NO DIFFICULTY MILD
DIFFICULTY MODERATE DIFFICULTY
SEVERE DIFFICULTY
UNABLE
1. Open a tight or new jar 1 2 3 4 5 2. Do heavy household chores (e.g.
wash floors) 1 2 3 4 5
3. Carry a shopping bag or briefcase 1 2 3 4 5 4. Wash your back 1 2 3 4 5 5. Use a knife to cut food 1 2 3 4 5 6. Recreational activities in which you
take some force or impact through your arm, shoulder or hand (e.g. golf, hammering, tennis etc.)
1
2
3
4
5
NOT AT ALL SLIGHTLY MODERATELY QUITE A BIT EXTREMELY
7. During the past week, to what extent has you arm, shoulder or hand problem interfered with your normal social activities with friends, family or groups?
1
2
3
4
5
NOT AT ALL
LIMITED SLIGHTLY LIMITED
MODERATELY LIMITED
VERY LIMITED UNABLE
8. During the past week, were you limited in your work or other regular daily activities as a result of you arm, shoulder or hand problem?
1
2
3
4
5
Rate the severity of these symptoms in the past week:
NONE MILD MODERATE SEVERE EXTREME
9. Arm, shoulder or hand pain 1 2 3 4 5 10. Tingling (pins and needles)in your
arm, shoulder or hand 1 2 3 4 5
NO DIFFICULTY MILD DIFFICULTY
MODERATE DIFFICULTY
SEVERE DIFFICULTY
UNABLE TO SLEEP
11. During the past week, how much difficulty have you had sleeping because of the pain in your arm, shoulder or hand?
1
2
3
4
5
WORK MODULE (optional): The following questions ask about the impact of your arm, shoulder or hand problem on your ability to work (including homemaking if that is your main work role). Please indicate what your job is: _______________________________________________________ I do not work. (You may skip this section) Please circle the number that best describes your physical ability in the past week at work:
Did you have any difficulty? NO DIFFICULTY
MILD DIFFICULTY
MODERATE DIFFICULTY
SEVERE DIFFICULTY
UNABLE
1. Using your usual technique for your work?
1 2 3 4 5
2. Doing your usual work because of your arm, shoulder or hand problem?
1
2
3
4
5
3. Doing your work as well as you would like?
1 2 3 4 5
4. Spending your usual amount of time doing your work?
1 2 3 4 5
SPORTS/PERFORMING ARTS MODULE (optional) The following questions ask about the impact of your arm, shoulder or hand problem on playing your musical instrument or sport or both. If you play more than one sport or musical instrument (or play both), please answer with respect to that activity which is most important to you. Please indicate the sport or instrument that is most important to you: _________________________ I do not play a sport or musical instrument. (You may skip this section) Please circle the number that best describes your physical ability in the past week playing sport or your musical instrument:
Did you have any difficulty? NO DIFFICULTY
MILD DIFFICULTY
MODERATE DIFFICULTY
SEVERE DIFFICULTY
UNABLE
1. Using you usual technique for playing sport or your instrument?
1 2 3 4 5
2. Playing sport or your instrument because of your affected arm, shoulder or hand problem?
1 2 3 4 5
3. Playing sport or your instrument as well as you would like?
1 2 3 4 5
4. Spending your usual amount of time practicing or playing sport or your musical instrument?
1 2 3 4 5
NAME: __________________ DATE: ______
Short Form – 12 (SF-‐12) This questionnaire asks for your views about your health. This information will help keep track of how
you feel and how well you are able to do your usual activities. Please answer every question by
marking one box. If you are unsure about how to answer, please give the best answer you can.
1. In general, would you say your health is:
Excellent
Very good
Good
Fair
Poor
The following items are about activities you might do during a typical day. Does your health now
limit you in these activities? If limited, how much?
Yes, limited a lot Yes, limited a
little
No, not
limited at all
2. Moderate activities such as moving a
table, pushing a vacuum cleaner ,
bowling or playing golf
3. Climbing several flights of stairs
During the past month, have you had any of the following problems with work or other regular
activities as a result of your physical health?
Yes, limited a
lot
Yes, limited a
little
No, not
limited at all
4. Accomplished less than you would like
5. Were limited in the kind of work or other
activities
During the past month, have you had any of the following problems with work or other regular
activities as a result of any emotional problems (such as feeling depressed or anxious)?
Yes, limited a
lot
Yes, limited a
little
No, not
limited at all
6. Accomplished less than you would like
7. Didn’t do work or other activities as
carefully as usual
8. During the past month, how much did pain interfere with your normal work (both outside of
the house and housework)?
Not at all
A little bit
Moderately
Quite a bit
Extremely
These questions are about how you feel and how things have been with you during the past
month. For each question, please give one answer that comes closest to the way you have
been feeling. How much of the time during the past month:
All of the
time
Most of
the
time
A good bit
of the time
A little
bit of
the
time
None
of the
time
9. Have you felt calm and peaceful?
10. Did you have a lot of energy?
11. Have you felt downhearted and blue?
12. During the past month, how much of the time has your physical health or emotional
problems interfered with you social activities (such as visiting with friends, relatives etc.)?
All of the time
Most of the time
Some of the time
A little of the time
None of the time
APPENDIX 10
MANUSCRIPT ACCEPTED FOR PUBLICATION IN THE AMERICAN JOURNAL
OF SPORTS MEDICINE: DO POSTOPERATIVE PLATELET-RICH PLASMA
INJECTIONS ACCELERATE HEALING AND EARLY FUNCTIONAL RECOVERY
AFTER ARTHROSCOPIC SUPRASPINATUS REPAIR?: A RANDOMIZED
CONTROLLED TRIAL
Do Postoperative Platelet-RichPlasma Injections Accelerate Early TendonHealing and Functional Recovery AfterArthroscopic Supraspinatus Repair?
A Randomized Controlled Trial
Allan Wang,*y PhD, FRACS, Philip McCann,z FRCS(Tr&Orth), Jess Colliver,§ BSc,Eamon Koh,|| FRANZCR, Timothy Ackland,§ PhD, Brendan Joss,§ PhD,Minghao Zheng,y PhD, and Bill Breidahl,{ FRANZCRInvestigation performed at St John of God Hospitaland University of Western Australia, Perth, Australia
Background: Tendon-bone healing after rotator cuff repair directly correlates with a successful outcome. Biological therapiesthat elevate local growth-factor concentrations may potentiate healing after surgery.
Purpose: To ascertain whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair siteimproves early tendon healing and enhances early functional recovery after double-row arthroscopic supraspinatus repair.
Study Design: Randomized controlled trial; Level of evidence, 1.
Methods: A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. After randomization, half thepatients received 2 ultrasound-guided injections of PRP to the repair site at postoperative days 7 and 14. Early structural healingwas assessed with MRI at 16 weeks, and cuff appearances were graded according to the Sugaya classification. Functionalscores were recorded with the Oxford Shoulder Score; Quick Disability of the Arm, Shoulder and Hand; visual analog scale forpain; and Short Form–12 quality-of-life score both preoperatively and at postoperative weeks 6, 12, and 16; isokinetic strengthand active range of motion were measured at 16 weeks.
Results: PRP treatment did not improve early functional recovery, range of motion, or strength or influence pain scores at anytime point after arthroscopic supraspinatus repair. There was no difference in structural integrity of the supraspinatus repairon MRI between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thicknessretear; 23% partial tear; 70% intact) at 16 weeks postoperatively (P = .35).
Conclusion: After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on 2 occasions does not improve earlytendon-bone healing or functional recovery.
Keywords: platelet-rich plasma; rotator cuff repair; growth factors; tendon healing; early functional recovery.
Despite the advent of new surgical techniques to improverotator cuff fixation to bone, failure of the tendon repairoften occurs.12,38 Tendon retears may be due to a specificreinjury at the repair site but also may reflect incompleteor failed primary healing after surgery.5,6
Sonnabend et al,37 in a primate model of rotator cuffrepair, showed that a significant proportion of Sharpeyfibers begin to reconstitute at 3 months with maturationat 4 months after surgery. Thus, the early tendon healingstage is critical for long-term success of rotator cuff repair.
Accelerated rotator cuff rehabilitation programs that allowactive exercises sooner than 3 to 4 months before earlytendon-bone healing occurs risk early failure.29,43
Hence, there has been increasing interest in adjuvantbiological therapies to improve early primary tendon heal-ing. In particular, many studies have investigated platelet-rich plasma (PRP) products, where a supra physiologicalconcentration of platelets is delivered to the tendon-bonerepair site at the time of surgery. Activated plateletsdegranulate to release multiple growth factors that modu-late the cascade of chemotaxis, cell proliferation, and dif-ferentiation, which assist in the tendon healing process.#
The American Journal of Sports Medicine, Vol. XX, No. XDOI: 10.1177/0363546515572602� 2015 The Author(s) #References 3, 11, 13, 15, 17, 21, 22, 25, 31.
1
AJSM PreView, published on March 19, 2015 as doi:10.1177/0363546515572602
Published studies reporting the use of PRP administra-tion have met with mixed success in improving outcomesafter rotator cuff repair. Appraisal of the literature is com-plicated by the range of treated injuries, varying from small,single-tendon tears to massive multitendon tears; concomi-tant use of acromioplasty or not7,19; and the formulation ofPRP used, which ranged from intratendon injection,20,32
spray application,33,35 or incorporation of a platelet-richfibrin matrix into the tendon repair site.2,7,16,40
A further variable affecting the efficacy of PRP is the tim-ing of delivery. All previous PRP augmented rotator cuffstudies to date have used time zero delivery at the time ofsurgical repair. After activation, platelets release growthfactors almost immediately with total elution within1 hour,1 and the half-life of growth factors is a matter ofminutes to hours.26 However, it has been acknowledgedthat biological augmentation of tendon repairs too early inthe tendon healing cascade may be ineffective.15 Differingclasses of growth factors are active at specific time points21;for example, animal studies have shown that application ofplatelet-derived growth factors at day 7 have a more pro-nounced effect on tendon cellular maturation and biome-chanical strength than earlier application.8 Growthfactors, including bone morphogenetic protein–13 (BMP-13), platelet-derived growth factor–B, and transforminggrowth factor–B1, are expressed maximally at days 7 and14,42 and the cytokine-mediated temporal expression of col-lagen types I and III increases from day 7 onward.9
Hence, timing for PRP delivery remains an importantconsideration for optimizing tendon healing. In this study,we hypothesized that delayed and repeated injection ofPRP at days 7 and 14 after surgery would first avoid thepotential dilution and washout effect of arthroscopic admin-istration and second, produce a sustained up-regulation ofthe tendon healing process. The purpose of this study wasto determine if this PRP delivery protocol would enhanceearly tendon healing and functional recovery after arthro-scopic supraspinatus tendon repair. The primary study out-come was improved early tendon healing as assessed bymagnetic resonance imaging (MRI). The secondary outcomewas patient-rated function as a measure of functionalrecovery.
METHODS
Patient Selection
Institutional ethics committee approval was granted forthis study. Patients with rotator cuff tears verified byMRI or ultrasound were identified over the period from
November 2011 to February 2013. A power calculationwas performed to determine the required number ofpatients to detect a significant difference of 1 Sugaya gradeclassification between the treatment and control groupsbased on previously published MRI classification scoresfor post–rotator cuff repair patients.38 The power analysisused an effect size of 0.769 (moderate effect), with signifi-cance of P \ .05, and a power of 80%, giving a minimumsample size of 56 participants (n = 28 participants ineach group). More participants (n = 60) were recruited toallow for attrition.
The inclusion criteria comprised the presence of a symp-tomatic full-thickness tear of supraspinatus in an activeadult identified by preoperative imaging and confirmed byarthroscopic evaluation. All patients also received a seriesof plain radiographs (anteroposterior, outlet, and axillaryviews) for evaluation of arthritic changes. Exclusion criteriaincluded patients with a history of previous rotator cuff sur-gery, subscapularis or infraspinatus tear identified on
*Address correspondence to Allan Wang, PhD, FRACS, Department of Orthopaedic Surgery, University of Western Australia, 35 Stirling Hwy, CrawleyWA 6009, Australia (email: [email protected]).
yDepartment of Orthopaedic Surgery, University of Western Australia, Crawley, Australia.zDepartment of Trauma and Orthopaedic Surgery, King Edward Building, Bristol Royal Infirmary, Bristol, UK.§School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Australia.||Department of Radiology, Fremantle Hospital, Fremantle, Australia.{Perth Radiological Clinic, Perth, Australia.
One or more of the authors has declared the following potential conflict of interest or source of funding: Arthrex provided a stipend for J.C., exercisephysiologist, to undertake the Biodex evaluations. Arthrex donated disposable syringes used in study protocol. M.Z. is a scientific consultant to OrthoCell,a biotech company, and holds a patent in tendon cell culture technique; A.W., M.Z., and T.A. have shares in OrthoCell.
Assessed for eligibility (N = 305)
Excluded (n = 239)● Workers’ compensation = 108● PASTA repairs = 31● >2 cm, not supraspinatus alone, or involving subscapularis/ infraspinatus = 73● OA (glenohumeral joint) = 27
Declined to participate (n = 6)
Lost to follow-up (n = 0)
Discontinued intervention (n = 0)
Allocated to arthroscopic double-row rotator cuff repair and postoperative US-guided PRP injections (n = 30)
Received allocated intervention (n = 30)
Did not receive allocated intervention (n = 0)
Analyzed (n = 30)
Excluded from analysis (n = 0)
Allocation
Analysis
Follow-up
Enrollment
Lost to follow-up (n = 0)
Discontinued intervention (n = 0)
Analyzed (n = 30)
Excluded from analysis (n = 0)
Allocated to arthroscopic double-row rotator cuff repair without postoperative US-guided PRP injections (n = 30)
Received allocated intervention (n = 30)Did not receive allocated intervention (n = 0)
Randomized (n = 60)
Figure 1. CONSORT (Consolidated Standards of ReportingTrials) flowchart. OA, osteoarthritis; PASTA, partial articularsupraspinatus tendon avulsion; PRP, platelet-rich plasma;US, ultrasound.
2 Wang et al The American Journal of Sports Medicine
preoperative imaging or arthroscopic evaluation; labraltear; significant degenerative glenohumeral osteoarthritis;contralateral shoulder symptoms; rheumatalogical, neuro-muscular, or autoimmune disease; cervical disc herniation;ongoing workers’ compensation claims; or contraindicationto postoperative MRI evaluation (Figure 1).
Surgical Technique
All surgery was performed by the senior author. All proce-dures were performed in the lateral decubitus positionunder general anesthesia with an interscalene nerve block.The arm was placed in 4 kg of traction and positioned in 30�of arm flexion and abduction. Initial diagnostic glenohum-eral arthroscopy was performed and the presence of a full-thickness supraspinatus tear confirmed. After debridementof the bursal tissue and tendon margins, the tear type wasassessed and tear size measured with a calibrated probewith 5 mm increments. Tears over 20 mm in the anteropos-terior dimension were excluded, as were partial tears.Supraspinatus tears associated with subscapularis or infra-spinatus tears were excluded from the study. After acromio-plasty, rotator cuff reconstruction was performed. Thefootprint was prepared with a full-radius resector to decor-ticate the greater tuberosity. A double-row suture-bridgerepair28 with bioabsorbable anchors was performed(Arthrex Bio-Corkscrew 5.5 mm–FT, Biocomposite Pushloc3.5 mm; Arthrex). The same reconstructive technique wasutilized in each case. Concomitant shoulder injuries weretreated as clinically or radiographically indicated. Acromio-clavicular joint arthropathy was treated with arthroscopicexcision of the lateral end of the clavicle, and long head ofbiceps tendinopathy was treated with tenotomy (Table 1).
Postoperative Protocol
All patients were immobilized in a sling (Ultrasling III;Don Joy) for 6 weeks postoperatively and followed a stan-dard rehabilitation program under the supervision of phys-ical therapists. This consisted of passive range of motionexercises in the first 6 weeks, followed by active assistedrange of motion exercises from 6 to 10 weeks, and finally,a guided strengthening program from 10 to 16 weeks. Allpatients followed this program consistently.
Randomization Procedure
Patients were reviewed on postoperative day 5 and, afterarthroscopic evaluation and confirmation study inclusioncriteria were met, randomized to PRP or control groups. Acomputer block permutation method was prepared to gener-ate a simple randomized computer-generated table of blocksof 10 (5 PRP; 5 control) stratified by the treating surgeon atthe 5-day postsurgical follow-up. Sixty consecutive patientsmeeting the study inclusion criteria and consenting to thestudy were randomized via the aforementioned procedure,with 30 in each arm of the study. The average age was59.1 years (range, 28-77 years). Patient demographics alongwith details of concomitant surgical procedures are illus-trated in Table 1.
Preparation of PRP
The group randomized to the treatment arm of the studyunderwent ultrasound-guided PRP injection to the rotatorcuff repair site on 2 separate occasions, at days 7 and 14after surgery. The platelet concentrate was obtained usingthe Arthrex Autologous Conditioned Plasma (ACP) system.A PRP injection was prepared from 10 mL of autologousperipheral blood. After the addition of 1 mL of Anticoagu-lant Citrate Dextrose Solution (ACD-A), the blood wasspun in a centrifuge (ROTOFIX 32 A; Andreas HettichGmbH & Co KG) at 1500 RPM for 5 minutes. After centri-fugation, the PRP supernatant (approximately 2-4 mL)was removed and stored in a separate sterile syringe inpreparation for point-of-care delivery.
The ACP system produces a platelet concentration ofapproximately 470,000 platelets/mL (2.13 greater thanthe level in whole blood), with an estimated concentrationof growth factor reported as 5 to 25 times that of normalphysiologic levels. It is free of both residual erythrocytesand leucocytes, which may impair local growth factoractivity by free radical activation.18,36 Immediately beforeinjection, the preparation was activated with 2 mL ofCaCl2.27 The injection was delivered at the tendon repairsite under direct visualization with ultrasound by anexperienced fellowship-trained musculoskeletal radiolo-gist. Needle placement was aided by the identification ofthe echogenic sutures at the tendon repair site (Figure2). The control group did not receive a placebo injection.
TABLE 1Group Demographics With Concomitant Procedures and Complicationsa
Tear Size, mm
Sex, Male/Female, n
Age, y,Mean (Range)
Acromioplasty,n
BicepsTenotomy, n
AcromioclavicularJoint Excision, n
Complications,n
Median(range)
Mean 6 SD
PRP group (n = 30) 11/19 59.8 (28-77) 30 3 4 0 15 (10-20) 14.60 6 3.78Control group (n = 30) 17/13 58.4 (38-76) 30 5 5 0 15 (10-20) 13.70 6 3.27
aPRP, platelet-rich plasma.
Vol. XX, No. X, XXXX Postoperative PRP Injections After Supraspinatus Repair 3
Outcome Assessments
Radiographic analysis was performed with MRI at 16weeks. All scans utilized a 1.5-T unit (Sonata MaestroClass; Siemens) with 40 mT/m gradient power. Multipleimages were obtained in oblique coronal, oblique sagittal,and axial planes with both short-tau inversion recovery(STIR) and turbo spin echo (TSE) T1-weighted sequence.MRI assessment was performed by an experiencedfellowship-trained musculoskeletal radiologist who hadnot performed the PRP injections and was blinded topatient allocation to treatment or control group. Multipleimages were evaluated and graded as per the Sugaya clas-sification (Figure 3).38
Outcomes were assessed clinically and radiologically.Patients were assessed using the Oxford Shoulder Score(OSS); Quick Disability of the Arm, Shoulder and Hand(QuickDASH); visual analog scale (VAS) for pain (notingmaximum pain in the prior 7-day period); and ShortForm–12 (SF-12) preoperatively and at 6, 12, and 16 weekspostoperatively. All assessors were blinded as to the
identity of the treatment and control groups, nor werethey involved in any stage of the recruitment or surgery.
Active range of motion was assessed at 16 weeks usinga goniometer. Absolute values were recorded for arm flex-ion, abduction, and external humeral rotation in both theoperated and unoperated shoulders, using anatomic land-marks for accuracy and consistency. Range of motion wasperformed within the participants’ pain tolerance to mini-mize any injury risk and discomfort.
Isokinetic strength was also assessed at 16 weeks withthe patient seated in a Biodex isokinetic dynamometer,and a series of standardized measurements were per-formed with the patient instructed to produce a maximummuscular force at speeds of 60 and 90 deg/s. Externalhumeral rotation was performed in the modified-neutralposition, with the elbow at 90� of flexion and the forearmin a neutral position throughout. Arm flexion was per-formed with the elbow fully extended. Values for bothpeak torque and total work performed over the range ofmotion were noted. Data were recorded as both absolutevalues and as a percentage of the scores obtained on thecontralateral, unoperated shoulder. A difference of 10%to 15% in the strength between shoulders is regarded asphysiologically normal in the general population and inthose patients undergoing surgery.4
Statistical Analysis
Values are presented as means with associated standarddeviations. A series of 2-factor, repeated-measures ANOVAswere performed to assess for difference between the treat-ment and control groups over time for continuous variables.For continuous data recorded at a single time point only,a series of independent t tests were performed, whereasa Mann-Whitney U test was employed for the MRI ratingprimary outcome variable. Statistical analyses used SPSSsoftware (IBM Corp). For all tests, P \ .05 was consideredsignificant.
RESULTS
All patients complied with the study protocol, and nopatient was lost to follow-up. There were no significantcomplications such as infection or neurological or vasculardeficit for any patient in either arm of the study. In thecontrol group, mean tendon tear size treated was1.37 cm, and in the PRP group, mean tendon tear size trea-ted was 1.46 cm. The adjunctive procedures of acromiocla-vicular joint excision and biceps tenotomy are shown inTable 1. No patient underwent a cortisone injection forpain, capsulitis, or bursitis within the study period.
Structural Evaluation
With use of the Sugaya classification, the grade of supra-spinatus tendon healing for the PRP and control group isreported in Table 2. In both groups, 23% of subjects hada partial-thickness tendon repair (Sugaya grade 3). No
Figure 2. Ultrasound image of needle placement directly atthe tendon repair site (arrow).
Figure 3. T1-weighted coronal magnetic resonance imagedisplaying Sugaya grade 1 appearance.
4 Wang et al The American Journal of Sports Medicine
full-thickness retears were noted in the PRP treatmentgroup; 2 (7%) full-thickness retears (Sugaya grades 4 and5) occurred in the control group.
One patient in the PRP treatment group did not toleratethe postoperative MRI scan and so underwent an ultra-sound performed by an experienced musculoskeletal radi-ologist. This tendon repair was intact and without anyevidence of thinning or discontinuity and so, for the purpo-ses of the study, was included in the grade 1 group of thatcohort. In the PRP treatment group, 23 subjects (77%)exhibited a healed repair or an intact repair with high sig-nal intensity (Sugaya grades 1 and 2), compared with 21subjects (70%) in the control group. A Mann-Whitney Utest demonstrated no difference (P = .351) between groupson MRI rating at 16 weeks (PRP group mean, 1.8 6 0.8;control group mean, 2.1 6 1.0).
Functional Scores
Outcome scores for all patients improved after surgery. At12 and 16 weeks postoperatively, the Oxford ShoulderScore (F = 75.803; df = 3; P \ .001), the QuickDASH (F= 53.939; df = 3; P \ .001), and the VAS pain scores (F= 75.499; df = 3; P \ .001) all improved significantlyfrom before surgery. Similarly, the SF-12 quality-of-lifeindicators (physical component score: F = 13.967; df = 3;P \ .001; mental component score: F = 5.401; df = 3; P =
.001) improved with time. There was, however, no statis-tical difference (P . .05) between the PRP treatment andcontrol groups for any of these functional scores at anytime point postoperatively (Table 3).
Strength
Isokinetic strength values were obtained for active armflexion and external rotation movements at 2 speeds. Val-ues were expressed as a percentage of the strengthrecorded in the contralateral shoulder. Within the controlgroup, the relative scores for arm flexion peak torque at90 and 60 deg/s were 68.7% and 75.4%, respectively, and75.6% and 74.0%, respectively, for external rotation peaktorque. Relative scores were similar in the PRP treatmentgroup for arm flexion peak torque at 90 and 60 deg/s (74.1%and 76.3%, respectively) and external rotation peak torque(72.1% and 77.3%, respectively). No group differences (P .
.05) for strength scores at 16 weeks after surgery were evi-dent (Table 4).
Range of Motion
The analysis revealed no significant differences (P . .05)in any active range of motion measure between the 2
TABLE 2Sugaya Classification of MRI Scans of Patient Treatment Groupsa
Sugaya Classificationb
Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
PRP group (n = 30) 12 (40.0) 11 (36.6) 7 (23.0) 0 (0) 0 (0)Control group (n = 30) 9 (30.0) 12 (40.0) 7 (23.0) 1 (3.3) 1 (3.3)
aValues are reported as n (%). PRP, platelet-rich plasma.bFrom Sugaya et al.38 Grade 1 = no tear; grade 2 = sufficient tendon thickness but with high signal change; grade 3 = insufficient thickness
but no tendon discontinuity; grade 4 = small full-thickness retear; grade 5 = large full-thickness retear.
TABLE 3Functional Scoresa
Postoperative
Variable Group Preoperative 6 wk 12 wk 16 wk
QuickDASH symptoms (transformed) PRP 42.27 6 17.06 51.17 6 19.54 33.14 6 19.27 22.58 6 14.36Control 37.16 6 20.38 53.48 6 13.27 36.33 6 17.40 17.23 6 13.56
VAS PRP 6.37 6 1.59 3.26 6 2.43 2.35 6 2.01 1.75 6 1.68Control 5.38 6 2.43 1.19 6 2.34 2.23 6 1.91 1.36 6 1.51
OSS PRP 27.63 6 6.90 23.57 6 9.61 33.38 6 8.93 38.17 6 7.19Control 30.68 6 7.76 21.48 6 6.61 32.53 6 6.92 40.37 6 5.12
SF-12PCS PRP 35.17 6 8.43 36.31 6 7.40 38.73 6 7.06 41.78 6 8.34
Control 37.92 6 7.97 34.98 6 5.75 39.08 6 6.94 43.08 6 6.26MCS PRP 52.16 6 12.24 49.87 6 12.94 52.75 6 11.90 53.81 6 11.21
Control 50.47 6 12.56 49.69 6 13.63 53.47 6 10.55 55.17 6 7.41
aValues are reported as mean 6 SD. MCS, mental component score; OSS, Oxford Shoulder Score; PCS, physical component score; PRP,platelet-rich plasma; QuickDASH, Quick Disability of the Arm, Shoulder and Hand; SF-12, Short Form–12; VAS, visual analog scale for pain.
Vol. XX, No. X, XXXX Postoperative PRP Injections After Supraspinatus Repair 5
groups at 16 weeks after surgery. Complete values are dis-played in Table 5.
DISCUSSION
The purpose of the study was to evaluate the efficacy ofa protocol of sequential PRP administration after arthro-scopic supraspinatus repair. All previous studies have uti-lized a single delivery of a PRP product at the time ofsurgery. The current protocol delivered a PRP productunder ultrasound guidance to the tendon repair site at 7and 14 days after surgery to avoid a possible dilution orwashout effect of PRP, which may occur with arthroscopicfluid lavage. This protocol also allows a potentiallyprolonged up-regulation of growth factors involved inthe tendon healing cascade. Our hypothesis was thatthis postsurgical and sequential PRP delivery protocolwould (1) improve rotator cuff healing and (2) accelerateearly functional recovery after arthroscopic rotator cuffrepair.
This study finds that at 16 weeks after surgery, no full-thickness tendon retears occurred in the PRP group; how-ever, there were 2 (7%) full-thickness retears in the controlgroup. Although this difference was not statistically
significant, our findings are consistent with previousreports. Castricini et al7 examined the effects of platelet-rich fibrin matrix augmentation in rotator cuff repair andreported the re-rupture rate was higher in the control group(10.5% vs 2.5%). In contrast, Gumina et al,16 using a novelplatelet-rich fibrin matrix allowing slow release of growthfactors on the tendon repair site, found a 14% retear ratein isolated posterosuperior cuff tears in the PRP group com-pared with 50% in the control group at 13 months. HoweverRodeo et al,34 also using platelet-rich fibrin matrix in 79patients undergoing arthroscopic cuff repair, found no dif-ference in tendon bone healing on ultrasound at 6 weeksand 12 weeks after surgery.
The secondary outcomes of this study were to evaluateearly functional recovery in patients receiving PRP treat-ment after supraspinatus repair. In a prospective random-ized controlled trial of 53 patients, Randelli et al33 reportedthat PRP administered by spray produced statistically bet-ter early function scores and strength at 3 months aftersurgery. No imaging was performed at this stage, althoughit was concluded that PRP administration accelerates earlyrecovery after surgery. Zumstein et al44 also showed anearly benefit of PRP administration with improved revas-cularization of the tendon-bone repair site. Doppler ultra-sonography was used to assess the vascularization indexof 20 shoulders at 6 and 12 weeks after surgery.44 At 6weeks, those shoulders treated with a leucocyte-rich PRPproduct showed significantly better vascularization; how-ever, this was not sustained at 12 weeks.
Our study can report that early functional recovery wasnot improved with a sequential postsurgical PRP deliveryprotocol. At 6, 12, and 16 weeks, clinical function scoreswere equivalent between PRP and control group partici-pants. Furthermore, objective testing of shoulder functionat 16 weeks showed no difference between groups in recov-ery of active arm flexion, abduction, or external rotationrange of motion. Similarly, isokinetic peak torque andthe work done through the active range of motion duringeach movement was not different between groups.
PRP delivery by injection under ultrasound guidanceinto the supraspinatus tendon repair site may be less
TABLE 4Group Mean Scores and t Test Results
for Strength Measures at 16 Weeks Postoperativelya
Variable GroupIsokinetic
Strength, % t P Value
Arm flexionPeak torque 90 deg/s –.122 .266
PRP 74.1 6 10.8Control 68.7 6 24.2
Total work 90 deg/s .107 .915PRP 55.5 6 23.2Control 56.3 6 34.2
Peak torque 60 deg/s –.190 .85PRP 76.3 6 22.0Control 75.4 6 22.0
Total work 60 deg/s –.150 .881PRP 61.7 6 21.8Control 60.8 6 27.4
External rotationPeak torque 90 deg/s .470 .640
PRP 72.2 6 15.7Control 75.6 6 37.5
Total work 90 deg/s .712 .371PRP 51.9 6 30.1Control 55.1 6 35.8
Peak torque 60 deg/s –.64 .525PRP 77.3 6 17.8Control 74.0 6 21.3
Total work 60 deg/s .277 .783PRP 59.8 6 24.3Control 62.3 6 44.0
aStrength was calculated as a percentage of the contralateral,unoperated arm. Results are reported as mean 6 SD. PRP,platelet-rich plasma.
TABLE 5Group Mean Scores and t Test Results
for Range of Motion for the Operated Limbat 16 Weeks Postoperativelya
Variable GroupRange of
Motion, deg t P Value
Arm flexion 1.274 .208PRP 144.8 6 22.8Control 151.8 6 19.8
Arm abduction 0.342 .734PRP 134.8 6 28.2Control 137.4 6 29.1
External rotation 0.69 .493PRP 41.1 6 10.2Control 42.8 6 9.3
aPRP, platelet-rich plasma.
6 Wang et al The American Journal of Sports Medicine
accurate than injection under arthroscopic visualization.However, the surgical technique employed in this studycomprised a double-row suture bridge technique, and theechogenic suture knots were readily identified on ultra-sound. Moreover, the oblique and interlocking sutures ofthe suture bridge potentially retain the injected PRP atthe repair site better than the single-row repair site tech-nique used in previous studies.33
As an imaging modality, ultrasound has been shown tobe reliable in obtaining a precise placement of PRP at thesite of tendon injury.41 PRP delivery by direct injectionunder ultrasound guidance has been used to treat injuriesof the Achilles tendon,10 the common extensor tendon ori-gin,23,24,30 and the rotator cuff. Kesikburun et al20 demon-strated that PRP injection to nonsurgically treat rotatorcuff tendinopathy and partial-thickness tendon tears hasno significant clinical benefit over saline injections at 3,6, 12, and 52 weeks. The findings of our study are consis-tent with this work, and even with a second PRP injection,there was no significant clinical or functional benefit up to16 weeks after surgery. Our study focus is early outcomes,however; definitive clinical outcomes require 12- to 24-month postoperative evaluation.
This study has some limitations to be acknowledged.First, the follow-up was limited to 16 weeks. It is possiblethat more structural tendon failures would have beenseen if MRI evaluation was repeated at a later time inter-val such as 12 months. However, it was the primary aim ofthis study to assess the effects of PRP treatment on theearly phases of tendon healing. Animal models have dem-onstrated that a significant proportion of Sharpey fibersat the tendon repair site have reconstituted and maturedat the bone-tendon repair by 3 to 4 months,37 thus support-ing the validity of assessment at the 16-week time point.
A second limitation is the nonblinding of subjects in bothPRP and control groups. As the study protocol required 2separate postsurgical injections, we considered that it wouldbe impractical to have patients agreeing to complete 2 pla-cebo injections. Patients in the PRP treatment group mayhave had the benefit of a placebo as well as a possiblePRP treatment effect in their clinical and functional evalu-ation. Similarly, those patients who did not receive injec-tions may have responded differently in clinical testing.The nonblinding of subjects could be expected to cause apositive bias in the PRP group; however, groups were equiv-alent in their study outcomes. MRI evaluation was per-formed by an independent musculoskeletal radiologist whohad not been involved in previous diagnostic imaging orPRP injections and was blinded to group allocation.
A further possible study limitation was the PRP productused in this study does not achieve the very high concentra-tion of platelets reported with some other PRP products.1,11,14
Sundman et al,39 in a laboratory study, suggested that mark-edly elevated supra physiological levels of platelets andgrowth factors may be of no additional benefit due to cell-surface receptor saturation or may actually be detrimentalto tendon healing.39 Optimal tendon healing requires notonly the appropriate concentration of growth factors butthat those growth factors be delivered at the appropriatetime in the tendon healing cascade to be maximally effective.
CONCLUSION
This study is the first to evaluate the efficacy of a postsur-gical PRP delivery protocol to improve healing and func-tional outcomes after arthroscopic rotator cuff repair.Sequential delivery of the specific injectable PRP prepara-tion used in this study under ultrasound guidance, at days7 and 14 after surgery, does not improve early rotator cuffhealing or functional recovery. Future research shouldinclude randomized controlled trials of other PRP productswith alternative delivery vehicles and dosing regimes.
REFERENCES
1. Arnoczky SP, Delos D, Rodeo SA. What is platelet-rich-plasma?
Oper Techn Sports Med. 2011;19(3):142-148.
2. Barber FA, Hrnack SA, Snyder SJ, et al. Rotator cuff repair healing
influenced by platelet-rich plasma construct augmentation. Arthros-
copy 2011;27:1029-1035.
3. Bedi A, Maak T, Walsh C, et al. Cytokines in rotator cuff degeneration
and repair. J Shoulder Elbow Surg. 2012;21(2):218-227.
4. Bigoni M, Gorla M, Guerrasio S, et al. Shoulder evaluation with isoki-
netic strength testing after arthroscopic rotator cuff repairs. J Shoul-
der Elbow Surg. 2009;18(2):178-183.
5. Boileau P, Brassart N, Watkinson DJ, et al. Arthroscopic repair of full-
thickness tears of the supraspinatus: does the tendon really heal?
J Bone Joint Surg Am. 2005;87:1229-1240.
6. Carpenter JE, Thomopoulos S, Flanagan CL, et al. Rotator cuff defect
healing: a biomechanical and histologic analysis in an animal model.
J Shoulder Elbow Surg. 1998;7(6):599-605.
7. Castricini R, Longo UG, De Benedetto M, et al. Platelet-rich plasma
augmentation for arthroscopic rotator cuff repair: a randomized con-
trolled trial. Am J Sports Med. 2011;39:258-265.
8. Chan BP, Fu SC, Qin L, Rolf C, Chan KM. Supplementation time
dependence of growth factors in promoting tendon healing. Clin
Orthop Relat Res. 2006;448:240-247.
9. Dahlgren LA, Mohammed HO, Nixon AJ. Temporal expression of
growth factors and matrix molecules in healing tendon lesions.
J Orthop Res. 2005;23(1): 84-92.
10. De Vos RJ, Weir A, van Schie HT, et al. Platelet-rich plasma injection
for chronic Achilles tendinopathy: a randomized controlled trial.
JAMA. 2010;303:144-149.
11. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth
factor analysis from platelet-rich plasma: implications for wound
healing. Plast Reconstr Surg. 2004;114:1502-1508.
12. Galatz LM, Ball CM, Teefey SA, et al. The outcome and repair integ-
rity of completely arthroscopically repaired large and massive rotator
cuff tears. J Bone Joint Surg Am. 2004;86:219-224.
13. Galatz L, Rothermich S, VanderPloeg K, Petersen B, Sandell L,
Thomopoulos S. Development of the supraspinatus tendon-to-bone
insertion: localized expression of extracellular matrix and growth fac-
tor genes. J Orthop Res. 2007;25(12):1621-1628.
14. Geaney LE, Arciero RA, DeBerardino TM, Mazzocca AD. The effects
of platelet-rich plasma on tendon and ligament: basic science and
clinical application. Oper Techn Sports Med. 2011;19(3):160-164.
15. Gulotta LV, Rodeo SA. Growth factors for rotator cuff repair. Clin
Sports Med. 2009;28:13-23.
16. Gumina S, Campagna V, Ferrazza G, et al. Use of platelet-leukocyte
membrane in arthroscopic repair of large rotator cuff tears: a prospec-
tive randomized study. J Bone Joint Surg Am. 2012;94(15):1345-1352.
17. Isaac C, Gharaibeh B, Witt M, Wright VJ, Huard J. Biologic
approaches to enhance rotator cuff healing after injury. J Shoulder
Elbow Surg. 2012;21(2):181-190.
18. Jiang N, Tan NS, Ho B, Ding JL. Respiratory protein-generated reac-
tive oxygen species as an antimicrobial strategy. Nat Immunol.
2007;8(10):1114-1122.
Vol. XX, No. X, XXXX Postoperative PRP Injections After Supraspinatus Repair 7
19. Jo CH, Kim JE, Yoon KS, et al. Does platelet-rich plasma accelerate
recovery after rotator cuff repair? A prospective cohort study. Am J
Sports Med. 2011;39:2082-2090.
20. Kesikburun SL, Tan AK, Yilmaz B, Yasxar E, Yazicioglu K. Platelet-rich
plasma injections in the treatment of chronic rotator cuff tendinop-
athy: a randomized controlled trial with 1-year follow-up. Am J Sports
Med. 2013;41(11):2609-2616.
21. Kobayashi M, Itoi E, Minagawa H, et al. Expression of growth factors
in the early phase of supraspinatus tendon healing in rabbits.
J Shoulder Elbow Surg. 2006;15:371-376.
22. Manning CN, Kim HM, Sakiyama-Elbert S, Galatz LM, Havlioglu N,
Thomopoulos S. Sustained delivery of transforming growth factor
beta three enhances tendon-to-bone healing in a rat model. J Orthop
Res. 2011;29:1099-1105.
23. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with
buffered platelet-rich plasma. Am J Sports Med. 2006;34:1774-1778.
24. Mishra AK, Skrepnik NV, Edwards SG, et al. Efficacy of platelet-rich
plasma for chronic tennis elbow: a double-blind, prospective, multi-
center, randomized controlled trial of 230 patients. Am J Sports
Med. 2014;42(2):463-471.
25. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon
and ligament healing. Sports Med. 2003;33(5):381-394.
26. Mooren RE, Hendriks EJ, van den Beucken JJ, et al. The effect of
platelet-rich plasma in vitro on primary cells: rat osteoblast-like cells
and human endothelial cells. Tissue Eng Part A. 2010;16(10):
3159-3172.
27. Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its
application in oral surgery: literature review. Tissue Eng Part B Rev.
2008;14(3):249-258.
28. Park MC, Elattrache NS, Ahmad CS, Tibone JE. ‘‘Transosseous-
equivalent’’ rotator cuff repair technique. Arthroscopy. 2006;22(12):
1360.e1-5.
29. Parsons BO, Gruson KI, Chen DD, Harrison AK, Gladstone J, Flatow
EL. Does slower rehabilitation after arthroscopic rotator cuff repair
lead to long-term stiffness? J Shoulder Elbow Surg. 2010;19(7):
1034-1039.
30. Peerbooms JC, Sluimer J, Bruijn DJ, Gosens T. Positive effect of an
autologous platelet concentrate in lateral epicondylitis in a double-
blind randomized controlled trial: platelet-rich plasma versus cortico-
steroid injection with a 1-year follow-up. Am J Sports Med.
2010;38(2):255-256.
31. Plate JF, Haubruck P, Walters J, et al. Rotator cuff injuries in professional
and recreational athletes. J Surg Orthop Adv. 2013;22(2):134-142.
32. Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N. Autologous
platelet rich plasma for arthroscopic rotator cuff repair. A pilot study.
Disabil Rehabil. 2008;30(20-22):1584-1589.
33. Randelli P, Arrigoni P, Ragone V, Aliprandi A, Cabitza P. Platelet rich
plasma in arthroscopic rotator cuff repair: a prospective RCT study,
2-year follow-up. J Shoulder Elbow Surg. 2011;20(4):518-528.
34. Rodeo SA, Delos D, Williams RJ, Adler RS, Pearle A, Warren RF. The
effect of platelet-rich fibrin matrix on rotator cuff tendon healing:
a prospective, randomized clinical study. Am J Sports Med.
2012;40(6):1234-1241.
35. Ruiz-Moneo P, Molano-Munoz J, Prieto E, Algorta J. Plasma rich in
growth factors in arthroscopic rotator cuff repair: a randomized, dou-
ble-blind, controlled clinical trial. Arthroscopy. 2013;29(1):2-9.
36. Scott A, Khan KM, Roberts CR, Cook JL, Duronio V. What do we
mean by the term ‘‘inflammation’’? A contemporary basic science
update for sports medicine. Br J Sports Med. 2004;38(3):372-380.
37. Sonnabend DH, Howlett CR, Young AA. Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br.
2010;92(4):586-594.
38. Sugaya H, Maeda K, Matsuki K, Moriishi J. Repair integrity and func-
tional outcome after arthroscopic double-row rotator cuff repair. A pro-
spective outcome study. J Bone Joint Surg Am. 2007;89(5):953-960.
39. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cyto-
kine concentrations are influenced by the cellular composition of
platelet-rich plasma. Am J Sports Med. 2011;39:2135-2140.
40. Weber SC, Kauffman JI, Parise C, Weber SJ, Katz SD. Platelet-rich
fibrin matrix in the management of arthroscopic repair of the rotator
cuff: a prospective, randomized, double-blinded study. Am J Sports
Med. 2013;41(2):263-270.
41. Wiegerinck JI, Reilingh ML, de Jonge MC, van Dijk CN, Kerkhoffs GM.
Injection techniques of platelet-rich plasma into and around the Achil-
les tendon: a cadaveric study. Am J Sports Med. 2011;39:1681-1686.
42. Wurgler-Hauri CC, Dourte LM, Baradet TC, et al. Temporal expres-
sion of 8 growth factors in tendon-to-bone healing in a rat supraspi-
natus model. J Shoulder Elbow Surg. 2007;16(suppl 5):S198-S203.
43. Zhang S, Li H, Tao H, et al. Delayed early passive motion is harmless
to shoulder rotator cuff healing in a rabbit model. Am J Sports Med.
2013;41(8):1885-1892.
44. Zumstein MA, Rumian A, Lesbats V, Schaer M, Boileau P. Increased
vascularization during early healing after biologic augmentation in
repair of chronic rotator cuff tears using autologous leukocyte- and
platelet-rich fibrin (L-PRF): a prospective randomized controlled pilot
trial. J Shoulder Elbow Surg. 2014;23(1):3-12.
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APPENDIX 11
MANUSCRIPT ACCEPTED FOR PUBLICATION IN THE JOURNAL OF
SHOULDER AND ELBOW SURGERY: EARLY POSTOPERATIVE REPAIR
STATUS AFTER ROTATOR CUFF REPAIR EVALUATION.CANNOT BE
ACCURATELY CLASSIFIED USING QUESTIONNAIRES OF PATIENT
FUNCTION AND ISOKINETIC STRENGTH EVALUATION
The University
Ethics Committ
J Shoulder Elbow Surg (2016) 25, 536-542
1058-2746/$ - s
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BASIC SCIENCE
Early postoperative repair status after rotatorcuff repair cannot be accurately classified usingquestionnaires of patient function andisokinetic strength evaluation
Jessica Colliver, BSca, Allan Wang, PhD, FRACSa,b,c,Brendan Joss, PhDa, Jay Ebert, PhDa,*, Eamon Koh, FRANZCRd,William Breidahl, FRANZCRe, Timothy Ackland, PhDa
aSchool of Sport Science, Exercise and Health, University of Western Australia, Crawley, Perth, WA, AustraliabDepartment of Orthopaedic Surgery, University of Western Australia, Crawley, Perth, WA, AustraliacSt John of God Hospital, Subiaco, Perth, WA, AustraliadDepartment of Radiology, Fremantle Hospital, Fremantle, WA, AustraliaePerth Radiological Clinic, Subiaco, Perth, WA, Australia
Background: This study investigated if patients with an intact tendon repair or partial-thickness retearearly after rotator cuff repair display differences in clinical evaluations and whether early tendon healingcan be predicted using these assessments.Methods: We prospectively evaluated 60 patients at 16 weeks after arthroscopic supraspinatus repair. Eval-uation included theOxford Shoulder Score, 11-itemversion of theDisabilities of theArm, Shoulder andHand,visual analog scale for pain, 12-item Short Form Health Survey, isokinetic strength, and magnetic resonanceimaging (MRI). Independent t tests investigated clinical differences in patients based on the Sugaya MRI ro-tator cuff classification system (grades 1, 2, or 3). Discriminant analysis determined whether intact repairs(Sugaya grade 1) and partial-thickness retears (Sugaya grades 2 and 3) could be predicted.Results: No differences (P < .05) existed in the clinical or strength measures. Although discriminant anal-ysis revealed the 11-item version of the Disabilities of the Arm, Shoulder and Hand produced a 97% true-positive rate for predicting partial thickness retears, it also produced a 90% false-positive rate whereby itincorrectly predicted a retear in 90% of patients whose repair was intact. The ability to discriminate be-tween groups was enhanced with up to 5 variables entered; however, only 87% of the partial-reteargroup and 36% of the intact-repair group were correctly classified.Conclusions: No differences in clinical scores existed between patients stratified by the Sugaya MRI clas-sification system at 16 weeks. An intact repair or partial-thickness retear could not be accurately predicted.Our results suggest that correct classification of healing in the early postoperative stages should involveimaging.
of Western Australia (RA/4/1/4872) Human Research
ee (HREC) approved this research.
*Reprint requests: Jay R. Ebert, PhD, School of Sport Science, Exer-
cise and Health, University of Western Australia, 35 Stirling Hwy,
Crawley, 6009, WA, Australia.
E-mail address: [email protected] (J. Ebert).
ee front matter � 2016 Journal of Shoulder and Elbow Surgery Board of Trustees.
/10.1016/j.jse.2015.09.019
Clinical scores cannot classify cuff status 537
Level of evidence: Basic Science Study, Validation of Patient Reported Outcome Instruments.� 2016 Journal of Shoulder and Elbow Surgery Board of Trustees.
Keywords: Rotator cuff repair surgery; shoulder; patient-reported outcome measures; isokinetic strength;
magnetic resonance imagingRotator cuff surgical repair is common, with in excess of250,000 performed each year.18 Despite advances in sur-gical techniques and the increasing use of adjunct biologictherapies to stimulate or enhance repair, or both, the post-operative failure rate remains a concern.3,8,9 Although pa-tients with retears or failed healing may experience areduction in pain, functional outcomes, including strengthlevels, are significantly lower compared with patients withevidence of completely healed tendons.6,10,16,20,32 Theseinferior functional results may be satisfactory for an olderor less active population, or both, but patients who require areturn to sport or work where physical strength is importantmay be dissatisfied with the outcome.
A primate model of rotator cuff repair showed that asignificant proportion of Sharpey fibers start to reconstituteat 3 months, with maturation seen at 4 months.29 Klugeret al24 reported that most recurrent tears occur in the first 3months after rotator cuff surgery, highlighting that thisearly phase of tendon healing up to 3 to 4 months post-operatively is critical for longer-term success. Earlyconfirmation of tendon healing is reassuring for the patientin the early postoperative stages. Likewise, identification ofimpaired healing or partial disruption of the tendon repaircould affect management after surgery. This may includemodifying the patient’s ongoing rehabilitation program,more focused patient education on potentially provocativeor damaging movements and activities, recommending re-strictions in future work and sport practices, ongoing sur-veillance of future patient symptoms and imaging, and evenconsideration for further surgery. Therefore, identifying thepresence of incomplete tendon healing at an early stageafter surgery using clinical and strength evaluation couldprove beneficial.
The routine use of postoperative imaging studies toevaluate the outcome of rotator cuff surgery can be costly.Ultrasound (US), although readily available and cost-effective, is operator dependent for accuracy.17,30 Mag-netic resonance imaging (MRI) is generally considered tobe superior to US2,11 but remains an expensive imagingmodality. Several researchers have attempted to determinewhether the clinical progress of a nonoperatively treatedrotator cuff tendon tear can be predicted using commonclinical shoulder assessments, albeit with limited suc-cess.1,23,25 At the time of writing, we are unaware of anyother studies that have investigated whether commonshoulder clinical assessments can predict the early post-operative success of rotator cuff repair surgery.
Therefore, this study aimed to (1) investigate if differ-ences in common shoulder patient-reported outcome (PRO)measures and isokinetic strength tests could be observedbetween patients with completely intact repairs or partial-thickness tendon retears, classified by MRI, at 16 weeksafter rotator cuff repair surgery; and (2) determine if thesePRO measures and strength tests could predict the early(16 weeks) postoperative success of rotator cuff repair.
Materials and methods
Patients
This prospective comparative study recruited 60 consecutive pa-tients with rotator cuff tears isolated to the supraspinatus (Table I).Patients were recruited between November 2011 and February2013 and were included if they presented with a symptomatic full-thickness tear of the supraspinatus, confirmed preoperatively byMRI or US and intraoperatively by arthroscopic evaluation. Pa-tients with supraspinatus partial tears or tears exceeding 20 mm inthe anteroposterior dimension were excluded, as were patientswith concomitant subscapularis or infraspinatus tears, or both,identified on preoperative US or MRI or intraoperative examina-tion. Patients were excluded if they had any or all of a history ofprevious rotator cuff surgery, labral tearing, significant osteoar-thritis of the glenohumeral joint, rheumatologic, neuromuscular,or autoimmune disease, or cervical disc herniation. Patients werefurther excluded if they presented with any contralateral shouldersymptoms or had ongoing workers’ compensation claims.
A priori power calculation based on our first study goal wasdetermined from the recommendations of Cohen.12 The minimalclinically important difference reported for the 11-item version ofthe Disability of the Arm, Shoulder and Hand (QuickDASH)questionnaire varies, ranging from 14.0 to 17.1 for patients withshoulder pathology,15,31,35 equating to an effect size of 0.75 to0.98. Therefore, to detect this degree of difference (effect size of0.85) with 80% power at a ¼ 0.05, we estimated that 18 patientsin each of the intact-repair (Sugaya grade 1) and partial-retear(Sugaya grade 2 and 3 pooled) groups would be required forthis study.
Surgical technique
All surgery was performed by the senior author (A.W.). Briefly, allprocedures were performed with the patient in the lateral decu-bitus position under general anaesthesia with an interscalene nerveblock. The arm was placed in 4 kg of traction and positioned in30� of arm flexion and abduction. The presence of a full-thicknesssupraspinatus tear was initially confirmed by diagnostic
Table I Group demographics with details of concomitantprocedures and complications
Variable Result (n ¼ 60)
SexMale 28Female 32
Age, mean (range) years 58.8 (28-77)Acromioplasty, No. 60Biceps tenotomy, No. 8Acromioclavicular joint excision, No. 9Complications, No. 0Supraspinatus tear size, mean (SD) mm 14 (4)
SD, standard deviation.
538 J. Colliver et al.
glenohumeral arthroscopy. Tear type and size were assessed usinga calibrated probe with 5-mm increments after d�ebridement ofbursal tissue and tendon margins.
After acromioplasty, rotator cuff reconstruction was per-formed. The footprint was prepared with a full-radius resector todecorticate the greater tuberosity. A double-row suture-bridgerepair28 technique with bioabsorbable anchors was performed(Arthrex Bio-Corkscrew 5.5 mm–FT, BioComposite PushLock3.5 mm; Arthrex, Naples, FL, USA) in all cases. Concomitantshoulder injuries were treated as clinically or radiographicallyindicated. Acromioclavicular joint arthropathy was treated witharthroscopic excision of the lateral end of the clavicle, and longhead of biceps tendinopathy was treated with tenotomy (Table I).
Postoperative management
All patients were immobilized in an abduction sling (UltraSlingIII; DonJoy, Carlsbad, CA, USA) for 6 weeks postoperatively andunderwent a standard rehabilitation program under the supervisionof a physical therapist. Briefly, patients undertook an initial6 weeks of passive range of motion exercises, followed by active-assisted range of motion exercises from 6 to 10 weeks, and aconservative strengthening program from 10 to 16 weeks. Allpatients followed the protocol consistently.
PRO measures
Four PRO measures were used at 16 weeks after surgery: (1) theOxford Shoulder Score (OSS); (2) the QuickDASH questionnaire;(3) a visual analog scale (VAS) for rating pain, and (4) the 12-item Short Form Health Survey (SF-12). The OSS is a 12-itemquestionnaire evaluating pain and function that has been validatedagainst general health and clinical measures and has demonstratedgood reliability in evaluating outcome after shoulder sur-gery.13,14,27 The QuickDASH is an 11-item questionnaire evalu-ating pain, symptoms, and physical function in patients withupper limb musculoskeletal disorders4 and has also demonstratedgood reliability, validity, and responsiveness.4,19 The VASrequired patients to rate their pain intensity on a 0- to 10-cmsliding scale (0 ¼ no pain, 10 ¼ worst pain imaginable) in thepreceding 24 hours. A 1.4-cm improvement on the VAS has beenreported as the minimal clinically important change in patientsundergoing nonoperative treatment for rotator cuff disease.33
Finally, the SF-12 is a generic health-related quality of lifescore36 that produces a physical (PCS) and mental (MCS)component subscale.
Isokinetic strength evaluation
Isokinetic strength was assessed at 16 weeks after surgery in allpatients using a Biodex Isokinetic Dynamometer (Biodex, Sys-tem 4, Shirley, NY, USA). Patients were seated with the trunkstabilized using rigid straps, and adjustments were made forhumeral and forearm length in accordance with each patient’sstature. Patients were instructed to undertake maximal concentricexternal/internal humeral rotation, followed by arm flexion, at anangular velocity of 60�/s. External/internal humeral rotation wasperformed in the modified-neutral position with the elbow in 90�
of flexion and the forearm in a neutral position. Arm flexion wasperformed with the elbow fully extended. Each trial consisted of3 maximal repetitions. Two trials on each upper limb were un-dertaken, alternating between the nonoperated and operatedlimbs, with the first trial always undertaken on the nonoperatedside. During each effort, patients were asked to perform to theirmaximal muscle strength, although without exerting themselvesto excessive pain. Verbal encouragement was provided, stan-dardized across all patients and trials. Patients were givenadequate rest between trials to minimize fatigue, although thiswas not standardized and was determined by the patient’s indi-vidual readiness to proceed. The peak torque (Nm) and time topeak torque (seconds) were obtained for all trials.
Radiologic evaluation
Radiographic analysis was performed using MRI at 16 weeks aftersurgery. A Sonata Maestro Class 1.5-T unit (Siemens, Erlangen,Germany) with 40 mT/m gradient power was used for all scans.Multiple images were obtained in oblique coronal, oblique sagittal,and axial planes with short-tau inversion recovery and turbo spinecho T1-weighted sequence. MRI assessment was performed by afellowship-trained musculoskeletal radiologist with more than20 years of experience. MRIs were graded according to the Sugayaclassification32: grade 1 ¼ no tear (sufficient tendon thickness withhomogeneously low intensity); grade 2 ¼ sufficient tendon thick-ness but with partial high intensity; grade 3¼ insufficient thicknessbut no tendon discontinuity; grade 4 ¼ small full-thickness retear(the presence of a minor discontinuity); grade 5 ¼ large full-thickness retear (the presence of a major discontinuity).
Statistical analysis
To address the first goal of this study, independent-sample t testswere used to determine if residual tendinopathy or partial-thickness tendon retears (Sugaya grade 2 or 3) led to poorerstrength and functional scores compared with an intact repair(Sugaya grade 1). Participants were grouped according to their 16-week postoperative MRI Sugaya grading (grade 1, 2, or 3), andthose with grade 4 or 5 were omitted from the analysis (n ¼ 2).Group means (standard deviation) for the Sugaya grading classi-fications are presented.
To address the second study goal, discriminant analysis wasused to determine if the Sugaya grading (presence and severity of
Table II Scores for the patient-reported outcome and isokinetic strength measures used for patients with intact (Sugaya grade 1) andpartial-thickness (Sugaya grade 2 and 3) supraspinatus tendon retears)
Variable Sugaya classification Group comparison
Grade 1(n ¼ 21)
Grade 2(n ¼ 23)
Grade 3(n ¼ 14)
Grade
1 vs 2 1 vs 3 2 vs 3
OSS 39.2 (6.4) 39.2 (5.1) 40.7 (8.0) 0.849 0.475 0.524VAS for pain 1.5 (1.4) 1.3 (1.3) 1.4 (2.0) 0.631 0.909 0.815QuickDASH 21.7 (12.4) 17.5 (11.9) 18.3 (17.8) 0.263 0.497 0.882SF-12
PCS 42.1 (8.1) 42.7 (5.8) 44.0 (9.3) 0.812 0.541 0.611MCS 53.7 (11.6) 55.3 (7.7) 54.9 (9.6) 0.615 0.749 0.914
Arm flexionPeak torque, Nm 77.1 (22.6) 76.5 (15.4) 74.9 (18.9) 0.922 0.768 0.780Time to peak torque, sec 0.53 (0.36) 0.56 (0.45) 0.52 (0.46) 0.393 0.312 0.387
External humeral rotationPeak torque, Nm 75.8 (21.2) 71.1 (16.8) 82.4 (21.8) 0.417 0.377 0.084Time to peak torque, sec 0.54 (0.45) 0.61 (0.42) 0.54 (0.42) 0.411 0.300 0.150
MCS, Mental Component Subscale; OSS, Oxford Shoulder Score; PCS, Physical Component Subscale; QuickDASH, 11-question Disability of the Arm, Shoulder
and Hand; SF-12, 12-item Short Form Health Survey; VAS, visual analog scale.) Data are presented as mean (standard deviation). Independent-sample t-test comparisons are provided between groups (P values).
Clinical scores cannot classify cuff status 539
tendinopathy or a partial-thickness retear) could be predictedusing PRO measures or strength data, or both. Linear combina-tions of predictor variables were formed to serve as the basis forclassifying patients into 2 groups: a partial-retear group (Sugayagrades 2 and 3) and an intact-repair group (Sugaya grade 1). Whendiscriminant analysis is used, it is recommended that the numberof variables should be used so that there are data for at least 3subjects per variable and that the number of variables should notexceed the number of individuals in the smallest group.7,34 Theserequirements were satisfied in our analysis. The discriminantanalysis used the method of Wilks lambda and a stepwise forwardinclusion model. Analyses were evaluated in terms of a higheigenvalue, high canonical correlation squared, low and significantWilks lambda (P < .001), and a high percentage of correctlyclassified participants, as suggested by Carter and Ackland,7 withsuccessful classification exceeding 80%. We began the analysiswith the variable that had the highest prediction (QuickDASH),and then added variables to a maximum of 5. Statistical analysiswas performed using SPSS 22.0 software (IBM Corp, Armonk,NY, USA). Statistical significance was determined at P < .05.
Results
Group means (standard deviations) are presented for pa-tients classified by Sugaya grades 1 (21 [36%]), 2 (23[40%]), or 3 (14 [24%]), and these groups were comparedat 16 weeks after surgery (Table II). One patient did nottolerate the postoperative MRI scan due to claustrophobiaand instead underwent an US performed by an experiencedmusculoskeletal radiologist. This tendon repair was intact,with no evidence of thinning or discontinuity, so for thepurpose of this study, it was included in the grade 1 Sugaya
classification. No significant differences (P > .05) in PROor isokinetic strength measures were observed among these3 groups by the Sugaya tear classification system at16 weeks after surgery (Table II).
Descriptive variables for the groups with intact (Sugayagrade 1) and residual tendinopathy and partial retear (Sugayagrade 2 and 3 pooled) are reported in Table III, with no dif-ferences (P > .05) observed at 16 weeks after surgery.Discriminant analysis results in Table IV revealed theQuickDASH produced a 97% true-positive rate for predictingpartial retears but also a 90% false-positive rate. The ability todiscriminate between groups was enhanced with up to 5 var-iables entered; however, only 87% of the partial-retear groupand 36% of the intact-repair group were correctly classified.
Discussion
This study evaluated the early clinical, functional, and MRIstatus of the supraspinatus tendon after arthroscopic sur-gical repair. Firstly, we investigated whether differences incommon shoulder PRO measures and isokinetic strengthtests could be observed between patients with intact repairsor partial-thickness tendon retears, classified by MRI, at16 weeks after rotator cuff repair surgery. Secondly, wedetermined whether early postsurgical tendon healing couldbe predicted using these PRO measures and strength tests.
This study found no significant difference in shoulderPRO and strength measures between patients stratified bythe Sugaya MRI classification system (grades 1, 2, or 3) forrotator cuff tears at 16 weeks after surgery. Studies haveinvestigated the diagnostic accuracy of clinical examination
Table III Mean scores for all patients classified with aSugaya grade 1, 2, or 3 outcome and for patients with intactrepairs (Sugaya grade 1) or with partial-thickness (Sugayagrade 2 and 3 pooled) supraspinatus tendon retears
Variable Intactrepair(n ¼ 21)
Partialretear(n ¼ 37)
Total(n ¼ 58)
Mean (SD) Mean (SD) Mean (SD)
Oxford Shoulder Score 39.2 (6.4) 40.1 (6.3) 39.6 (6.3)Visual analogscale for pain
1.5 (1.4) 1.4 (1.6) 1.4 (1.5)
QuickDASH 21.7 (12.4) 18.1 (14.6) 19.2 (13.7)SF-12 (PCS) 42.1 (8.1) 43.2 (7.5) 42.6 (7.6)SF-12 (MCS) 53.7 (11.6) 55.1 (8.1) 54.5 (9.6)Arm flexionPeak torque, Nm 77.1 (22.6) 76.0 (17.0) 76.5 (18.9)Time to peaktorque, sec
0.53 (0.36) 0.52 (0.44) 0.52 (0.41)
External humeralrotationPeak torque, Nm 75.8 (21.2) 75.0 (19.9) 75.7 (20.0)Time to peaktorque, sec
0.54 (0.45) 0.60 (0.42) 0.58 (0.43)
MCS, Mental Component Subscale; PCS, Physical Component Subscale;
QuickDASH, 11-item version of the Disabilities of the Arm, Shoulder and
Hand; SD, standard deviation; SF-12, 12-item Short Form Health
Survey.
540 J. Colliver et al.
for rotator cuff pathology21-23 and concluded that mostclinical tests are inaccurate. This study showed that clinicalevaluation is also inaccurate after surgery in differentiatinga completely intact supraspinatus tendon repair from arepair with residual tendinopathy or partial-thickness retearat 16 weeks after surgery. In this study, all concomitantpathology (lesions of the long head of biceps, acromialspurs and acromioclavicular arthropathy) that might haveaffected the outcome evaluations had been treated at thetime of surgery.
Although discriminant analysis revealed that theQuickDASH produced a 97% true-positive rate for pre-dicting partial retears, it also produced a 90% false-positiverate whereby it incorrectly predicted a retear in 90% ofpatients whose repaired tendons were in fact intact. Theaddition of other shoulder PRO measures or isokineticstrength evaluations did not greatly improve the capabilityof predicting the patient’s early tendon repair outcome.This study concludes that combining such measures doesnot give confidence in the diagnosis of partial-thicknesstendon retears. Some form of imaging assessment (MRI orUS) should be used if necessary for the purpose of diag-nosing residual tendinopathy or partial-thickness tendonretearing after arthroscopic supraspinatus repair.
However, the early use of shoulder-specific PRO mea-sures or strength evaluations remain important in guidingthe rehabilitation process after rotator cuff repair as well as
the patient’s specific return to work or sport. Although notspecific, these measures appear sensitive for identifyingincomplete tendon tearing at 16 weeks after surgical repair.Nho et al26 reported that 100% of retears occurred in thefirst 3 months after surgery. Kluger et al24 reported thatmost early postoperative retears appear to be a failure toheal and that repair site integrity at 6 months was a pre-dictor of 7-year clinical outcome. On the basis of our re-sults, if a patient has a QuickDASH score that is greaterthan the mean value we report at 16 weeks after surgery,then incomplete healing or partial-thickness retearing of thetendon requires exclusion by an imaging assessment.Although these results suggest that PRO measures andshoulder strength in a patient with a completely intactrepair is equivalent to that of a partial-thickness tendonretear at 16 weeks after surgery, the natural history inongoing high-demand work or sport is for partial tears todeteriorate. Therefore, early diagnosis of a failing cuffrepair by subsequent imaging in these patients may allowfor a decelerated rehabilitation program or vocationalcounselling on restricted work duties and prognosis.
This study has some acknowledged inherent limitations.Firstly, the patient follow-up was limited to 16 weeks. In aprimate model of rotator cuff repair, Sonnabend et al29
reported that a significant proportion of Sharpey fibersstart to reconstitute at 3 months, with maturation seen at 4months. However, if clinical, functional and MRI evalua-tions were to be repeated at a later time (such as12 months), it is possible that more structural tearing mightbe observed, contributing to more pain, diminished func-tion, and improved diagnostic accuracy of the combinedtesting protocol. Although the primary aim of this studywas to assess early postoperative tendon healing, futureresearch may include a longer-term follow-up.
A second limitation is that the PRO instruments we usedare used routinely through our clinical practice andresearch, and we appreciate other shoulder-specific scoresare available. It is possible that differences (or an improvedpredictive capacity) may be observed in other clinical andfunctional shoulder evaluations.
Thirdly, strength tests also have some inherent limita-tions because they are unable to differentiate between truemuscular weakness, muscular inhibition, and pain-relatedweakness.5 The results of the isokinetic strength tests alsorely on the patient making a maximal effort. Clear, stan-dardized instructions and verbal encouragement were pro-vided to all participants, but we acknowledged that this wasthe first time many of the patients would have maximallystressed their operated-on limb since surgery and that somemay have been hesitant to exert maximal effort. However,Bigoni et al5 reported that isokinetic strength testing is apowerful tool for evaluating strength after rotator cuffsurgery, so it may be that alternate testing protocols,incorporating shoulder abduction, may more accuratelydiscriminate between groups. Although maximal loading ofthe supraspinatus during shoulder abduction may be more
Table IV Discriminant analysis for variables predicting an intact repair (grade 1 Sugaya classification) or partial-thickness tendonretear (grade 2 and 3 Sugaya classification)
Prediction variables enteredy Statistic) Number classified (%)
Actual groupmembership
Predicted group membership
EV CC WL SigIntact repair(n ¼ 21)
Partial retear(n ¼ 37)
A. QuickDASH 0.011 0.104 0.989 0.465 Intact repair 2 (10) 19 (90)Partial retear 1 (3) 30 (97)
B. QuickDASH, ER Pk Tq 0.034 1.82 0.967 0.429 Intact repair 4 (18) 18 (82)Partial retear 3 (10) 28 (90)
C. QuickDASH, ER Pk Tq, OSS 0.039 0.194 0.962 0.594 Intact repair 5 (23) 17 (77)Partial retear 4 (13) 27 (87)
D. QuickDASH, ER Pk Tq, OSS, TPT ER 0.045 0.207 0.957 0.717 Intact repair 7 (32) 15 (68)Partial retear 4 (13) 26 (87)
E. QuickDASH, ER Pk Tq, OSS,TPT ER, AF Pk Tq
0.045 0.207 0.957 0.837 Intact repair 8 (36) 14 (64)Partial retear 4 (13) 26 (87)
OSS, Oxford Shoulder Score; QuickDASH, 11-item version of the Disabilities of Arm, Shoulder and Hand.) EV, eigenvalue; CC, canonical correlation; WL, Wilks lambda; Sig, prediction significance of the discriminant function.y ER Pk Tq, peak torque for humeral external rotation at 60�/s; AF Pk Tq, peak torque for arm flexion at 60�/s; TPT ER, time to peak torque in humeral
external rotation.
Clinical scores cannot classify cuff status 541
specific for eliciting pain and weakness, the aim of thisstudy was to evaluate whether these tests could predictearly (16-week) outcome, which we consider too early tomaximally stress the supraspinatus. Again, this also high-lights the need for longer-term evaluation.
Finally, our sample size had 80% power to detect only alarge effect size of 0.85 as estimated from prior studies, andtherefore, we can be confident that our data provide evi-dence that such large differences in outcome betweengroups do not exist. We may have failed to detect smallergroup differences with the available sample size.
Conclusion
This study found no significant difference in the shoul-der PRO measures used or in the isokinetic strengthevaluation between patient groups stratified by theSugaya MRI rotator cuff classification system at16 weeks after surgery. Furthermore, the presence of anintact repair or partial-thickness tendon retear after ro-tator cuff surgery could not be accurately predicted bythese clinical and functional shoulder evaluations at16 weeks. Our results suggest that if accurate classifi-cation of tendon healing is required in the early stageafter rotator cuff surgery, then medical imaging shouldbe used. This will give confidence in patient manage-ment of appropriate return to work or sport rehabilitationprograms. Reliance on PRO measures and functionalscores alone to make an accurate assessment is notsupported by our data.
Acknowledgments
We thank Arthrex for their financial support in under-taking the clinical evaluations for this study.
Disclaimer
Financial support was provided by Arthrex to assist inthe clinical evaluations for this study. The authors, theirimmediate families, and any research foundations withwhich they are affiliated have not received any financialpayments or other benefits from any commercial entityrelated to the subject of this article.
References
1. Ainsworth R, Lewis J. Exercise therapy for the conservative man-
agement of full thickness tears of the rotator cuff: a systematic review.
Br J Sports Med 2007;41:200-10. http://dx.doi.org/10.1136/bjsm.2006.
032524
2. Ardic F, Kahraman Y, Kacar M, Kahraman MC, Findikoglu G,
Yorgancioglu ZR. Shoulder impingement syndrome: relationships be-
tween clinical, functional, and radiologic findings. Am J Phys Med
Rehabil 2006;85:53-60. http://dx.doi.org/10.1097/01.phm.0000179518.
85484.53
3. Barber A, Hrnack SA, Snyder SJ, Hapa O. Rotator cuff repair healing
influenced by platelet-rich plasma construct augmentation. Arthros-
copy 2011;27:1029-35. http://dx.doi.org/10.1016/j.arthro.2011.06.010
542 J. Colliver et al.
4. Beaton DE, Wright JG, Katz JN, Upper Extremity Collaborative
Group. Development of the QuickDASH: comparison of three item-
reduction approaches. J Bone Joint Surg Am 2005;87:1038-46.
http://dx.doi.org/10.2106/JBJS.D.02060
5. Bigoni M, Gorla M, Guerrasio S, Brignoli A, Cossio A, Grillo P, et al.
Shoulder evaluation with isokinetic strength testing after arthroscopic
rotator cuff repairs. J Shoulder Elbow Surg 2009;18:178-83. http://dx.
doi.org/10.1016/j.jse.2008.09.002
6. Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM,
Krishnan SG. Arthroscopic repair of full-thickness tears of the
supraspinatus: does the tendon really heal? J Bone Joint Surg Am
2005;87:1229-40. http://dx.doi.org/10.2106/JBJS.D.02035
7. Carter JE, Ackland TR. Sexual dimorphism in the physiques of world
championship divers. J Sports Sci 1998;16:317-29.
8. Charousset C, Bellaiche L, Kalra K, Petrover D. Arthroscopic repair of
full-thickness rotator cuff tears: is there tendon healing in patients
aged 65 years or older? Arthroscopy 2010;26:302-9. http://dx.doi.org/
10.1016/j.arthro.2009.08.027
9. Cheung EV, Silverio L, Sperling JW. Strategies in biologic augmen-
tation of rotator cuff repair: a review. Clin Orthop Relat Res 2010;468:
1476-84. http://dx.doi.org/10.1007/s11999-010-1323-7
10. Cho NS, Rhee YG. The factors affecting the clinical outcome and
integrity of arthroscopically repaired rotator cuff tears of the shoulder.
Clin Orthop Surg 2009;1:96-104. http://dx.doi.org/10.4055/cios.2009.
1.2.96
11. Codsi MJ, Rodeo SA, Scalise JJ, Moorehead TM, Ma CB. Assessment
of rotator cuff repair integrity using ultrasound and magnetic reso-
nance imaging in a multicenter study. J Shoulder Elbow Surg 2014;23:
1468-72. http://dx.doi.org/10.1016/j.jse.2014.01.045
12. Cohen J. Statistical power analysis for the behavioral sciences. Hill-
sdale, NJ: Lawrence Erlbaum Associates; 1988 (ISBN No. 978-
0805802832).
13. Dawson J, Fitzpatrick R, Carr A. Questionnaire on the perceptions of
patients about shoulder surgery. J Bone Joint Surg Br 1996;78:593-
600.
14. Dawson J, Hill G, Fitzpatrick R, Carr A. The benefits of using patient-
based methods of assessment. Medium-term results of an observa-
tional study of shoulder surgery. J Bone Joint Surg Br 2001;83:
877-82.
15. Franchignoni F, Vercelli S, Giordano A, Sartorio F, Bravini E,
Ferriero G. Minimal clinically important difference of the disabilities
of the arm, shoulder and hand outcome measure (DASH) and its
shortened version (QuickDASH). J Orthop Sports Phys Ther 2014;44:
30-9. http://dx.doi.org/10.2519/jospt.2014.4893
16. Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The
outcome and repair of completely arthroscopically repaired large and
massive rotator cuff tears. J Bone Joint Surg Am 2004;86:219-24.
17. Goldberg JA, Bruce WJ, Walsh W, Sonnabend DH. Role of commu-
nity diagnostic ultrasound examination in the diagnosis of full-
thickness rotator cuff tears. ANZ J Surg 2003;73:797-9. http://dx.
doi.org/10.1046/j.1445-2197.2003.02790.x
18. Gulotta LV,Rodeo SA.Growth factors for rotator cuff repair. Clin Sports
Med 2009;28:13-23. http://dx.doi.org/10.1016/j.csm.2008.09.002
19. Gummesson C, Ward MM, Atroshi I. The shortened disabilities of the
arm, shoulder and hand questionnaire (QuickDASH): validity and
reliability based on responses within the full-length DASH. BMC
Musculoskelet Disord 2006;7:44. http://dx.doi.org/10.1186/1471-
2474-7-44
20. Harryman DT 2nd, Mack LA, Wang KY, Jackins SE, Richardson ML,
Matsen FA 3rd. Repairs of the rotator cuff. Correlation of functional
results with integrity of the cuff. J Bone Joint Surg Am 1991;73:982-9.
21. Hegedus EJ, Goode A, Campbell S, Morin A, Tamaddoni M,
Moorman CT 3rd, et al. Physical examination tests of the shoulder: a
systematic review with meta-analysis of individual tests. Br J Sports
Med 2008;42:80-92. http://dx.doi.org/10.1136/bjsm.2007.038406.
discussion 92.
22. Hegedus EJ, Goode AP, Cook CE, Michener L, Myer CA, Myer DM,
et al. Which physical examination tests provide clinicians with the
most value when examining the shoulder? Update of a systematic
review with meta-analysis of individual tests. Br J Sports Med 2012;
46:964-78. http://dx.doi.org/10.1136/bjsports-2012-091066
23. Hughes PC, Taylor NF, Green RA. Most clinical tests cannot accu-
rately diagnose rotator cuff pathology: a systematic review. Aust J
Physiother 2008;54:159-70. http://dx.doi.org/10.1016/S0004-9514(08)
70022-9
24. Kluger R, Bock P, Mittlbock M, Krampla W, Engel A. Long-term
survivorship of rotator cuff repairs using ultrasound and magnetic
resonance imaging analysis. Am J Sports Med 2011;39:2071-81.
http://dx.doi.org/10.1177/0363546511406395
25. Murrell GA, Walton JR. Diagnosis of rotator cuff tears. Lancet 2001;
357:769-70.
26. Nho SJ, Shindle MK, Adler RS, Warren RF, Altchek DW,
MacGillivray JD. Prospective analysis of arthroscopic rotator cuff
repair: subgroup analysis. J Shoulder Elbow Surg 2009;18:697-704.
http://dx.doi.org/10.1016/j.jse.2008.11.018
27. Olley LM, Carr AJ. The use of a patient-based questionnaire (the
Oxford Shoulder Score) to assess outcome after rotator cuff repair.
Ann R Coll Surg Engl 2008;90:326-31. http://dx.doi.org/10.1308/
003588408X285964
28. Park MC, Elattrache NS, Ahmad CS, Tibone JE. ‘‘Transosseous-
equivalent’’ rotator cuff repair technique. Arthroscopy 2006;22:1360.
e1-1365.e5. http://dx.doi.org/10.1016/j.arthro.2006.07.017.
29. Sonnabend DH, Howlett CR, Young AA. Histological evaluation of
repair of the rotator cuff in a primate model. J Bone Joint Surg Br
2010;92:586-94. http://dx.doi.org/10.1302/0301-620X.92B4.22371
30. Sonnabend DH, Hughes JS, Giuffre BM, Farrell R. The clinical role of
shoulder ultrasound. Aust N Z J Surg 1997;67:630-3.
31. Sorensen AA, Howard D, Tan WH, Ketchersid J, Calfee RP. Minimal
clinically important differences of 3 patient-rated outcomes in-
struments. J Hand Surg Am 2013;38:641-9. http://dx.doi.org/10.1016/
j.jhsa.2012.12.032
32. Sugaya H, Maeda K, Matsuki K, Moriishi J. Repair integrity and
functional outcome after arthroscopic double-row rotator cuff repair. A
prospective outcome study. J Bone Joint Surg Am 2007;89:953-60.
http://dx.doi.org/10.2106/JBJS.F.00512
33. Tashjian RZ, Deloach J, Porucznik CA, Powell AP. Minimal clinically
important differences (MCID) and patient acceptable symptomatic
state (PASS) for visual analog scales (VAS) measuring pain in patients
treated for rotator cuff disease. J Shoulder Elbow Surg 2009;18:927-
32. http://dx.doi.org/10.1016/j.jse.2009.03.021
34. Tatsuoka MM. Multivariate analysis; techniques for educational and
psychological research. New York: Wiley; 1971 (ISBN No.
0471845906).
35. van Kampen DA, Willems WJ, van Beers LW, Castelein RM,
Scholtes VA, Terwee CB. Determination and comparison of the
smallest detectable change (SDC) and the minimal important
change (MIC) of four-shoulder patient-reported outcome measures
(PROMs). J Orthop Surg Res 2013;8:40. http://dx.doi.org/10.1186/
1749-799X-8-40
36. Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health
Survey: construction of scales and preliminary tests of reliability and
validity. Med Care 1996;34:220-33.