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Aenor J. Sawyer, MDAsst. Clinical Professor

Dept of Orthopaedic SurgeryUCSF2012

Disclosures� Textbook: Bone Densitometry in Growing Patients:

Guidelines for Clinical Practice� Springer

� Otherwise:� None related to this Topic

Acknowledgements� Colleagues and Conference Organizers

� Images: Altas of Osteoporosis, Eric Orwell� © Copyright Current Medical Group a part of Springer

Science+Business Media 2009

� International Osteoporosis Foundation� Slide Kits and Publications for Patients and Physicians

Outline1. Introduction2. Vertebral Compression Fx

IncidenceConsequences

3. Bone Health Intervention Evaluation Treatment

4. Prevent the next Fracture

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Fractures: Associated with morbidity and mortality

7Cooper C, Am J Med, 1997;103(2A):12S-17S

40%Unable to walk independently

30%Permanentdisability

20%Death within

one year

80%One year after a

hip fracture:Unable to carry out at least one independent activity of daily living

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Increased Risk of Additional FxsRisk for additional fxs after one OP

fracture

1 VCF = 5 fold inc. in risk of 2nd VCFPrior hip fx = 10 fold inc. of 2nd hip fxAnkle fx = 1.5 fold inc risk hip fxKnee fx = 3.5 fold inc risk of hip fxOlecranon fx = 4.1 fold inc risk of hip fxLumbar spine fx = 4.8 fold inc risk of hip fx

SO… How do we intervene?Prevention of underlying skeletal insufficiencyPrevention of First FracturePrevention of Subsequent Fractures

These fractures are commonand have bad consequences:• increased morbidity• increased mortality• increased risk of recurrence

Osteoporosis�A disease characterized

by low bone mass and micro-architectural deterioration of bone tissue leading to reduced bone strength and a consequent increase in fracture risk.

10 year Hip Fracture Probability (%)

Femoral BMD T-score (SD)-3 -2 -1 0 10

10

20

50

60

70

80Age

(years)Women

Fracture risk depends on age and BMD

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Ability of bone to withstand load:Bone quality

Bone density is felt to acct for approx 60% of susceptibility to fracture,

Other determinants of bone strength� Morphometry, Geometry – diameter, length� Micro-architecture – cortical thickness and

porosity, arrangement and # of trabeculae. � Direction and extent of crosslinking of collagen

Load characteristicsDirection, amount and rate of load application are important in whether bone fails under load.

� With cyclical loading also consider magnitude, frequency of loading and interval repair periods

BONE: Acquisition and Loss

Age in Years

10 20 30 40 50 60 70 80 90

ActiveGrowth

SlowLoss

RapidLoss

Less RapidLoss

Peripubertalperiod

Peak bone mass

Early post-menopausal loss

Fracture threshold

Heaney RP. Osteoporosis Int 2000; 11: 985-1009

Influences on Bone Mass

Illness

MalnutritionMedication

ETHNICITY

Age-related changes in geometry Adaptation to maintain whole bone strength

Seeman. Lancet 2002; 359: 1841-50 Seeman. N Engl J Med. 2003; 349:320-3

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Age v. Mechanical PropertiesAge-Related Degradation of Mechanical Properties

Mechanical Property

Age-Related Decline, % per decade

Modulus 1.5–4Strength 2.1–5Ultimate tensile strain 5.1–9

Energy absorption (work) 6.8–12

Fracture toughness 4.1Impact energy 300

•Tissue-level mechanical properties degrade with age, as early as age 20 •Stiffness and strength:

• degrade 1% to 5% per decade

•Ductility and toughness :• more severe degradation of 8% to 12% per decade

•Age-related changes in collagen cross-linking, formation of advanced glycation end products, and increases in mineralization and porosity all affect tissue stiffness and strength, but more importantly these factors have an inordinate effect on tissue ductility and fragility.

20-year-old 80-year-old

Age-related changes in femoral neck cortex and association with hip fracture

Those with hip fractures have:• Preferential thinning of the inferior anterior cortex• Increased cortical porosity

Bell et al. Osteoporos Int 1999; 10:248-57

Jordan et al. Bone, 2000; 6:305-13

Mayhew et al, Lancet 2005

Age-related changes in trabecular microarchitecture

� Decreased bone volume, trabecular thickness and number

� Decreased connectivity

� Decreased mechanical strength

Image courtesy of David Dempster

Age-related changes in bone properties associated with fracture risk = decreased quantity and quality� Decreased bone mass and

BMD� Altered geometry� Altered architecture� Cortical thinning� Cortical porosity� Trabecular deterioration Images from L. Mosekilde, Technology and

Health Care. 1998

young

elderly

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Why are vertebra so susceptible?

Primarily Trabecularbonewhich has5x turnover rate of cortex.

Bone loss often occurs earliest where turn over is highest.

Vertebral compression fractureso Most common osteoporotic

fracture type, o Signif Morbidity and Mortalityo Deformity: Insidious, progressiveo Associated with

- Deformity, height loss, back pain- Impaired breathing

o Often silent, undetectedo Predict future spine and hip

fractures22

Possible causes of VCFs� Primary osteoporosis – changes with aging and Postmenopausal� Secondary osteoporosis� Drug-induced (corticosteroids, tobacco, barbituates, heparin)� Endocrine (hyperparathyroidism, diabetes)� Miscellaneous (renal failure, COPD, rheumatoid arthritis, hepatic

disease or transplant)� Osteolytic lesions� Multiple Myeloma� Bone metastases� Paget’s disease

� TraumaMany trauma cases are misclassified� Many have low bone mass and low VitD

Merck Manual, 16th ed., 1992The spine in Paget’s diseaseby Dell’Atti, C.; Cassar-Pullicino, V. N.; Lalam, R. K.; Tins, B. J.; Tyrrell, P. N. M.Journal: Skeletal Radiology Vol. 36 Issue 7

Presentation of VCFAcute Event:� Sudden onset of back pain

with little or no traumaChronic Manifestations:� Loss of height (½”/yr ) or

>1.5cm over past 2 yrs� Spinal deformity

(“Dowager’s hump”)� Protuberant abdomenGold et al., Osteoporosis 1996,2001

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CG

Biomechanics of Pathologic Spine Fractures

•Center of gravity (CG) moves forward•Large bending moment

created•Posterior muscles and

ligaments must counterbalance increased bending•Anterior spine must resist

larger compressive stresses

White III and Panjabi 1990

� Knees bend, pelvis tilts forward to counteract forward bending

�Change in balance1�Decrease in gait velocity1� Increased muscle fatigue1� Increased risk of falls and

additional fractures2

Biomechanics after VCFMay Increase fall risk

1 Gold et al., Osteoporosis 2001 2 Ross et al., Annals Int Med 1991

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Increased MortalityProspective study of 9,575 women

followed > 8 years demonstrated:� Patients with VCF have a 23-34% increased mortality

rate compared to patients without VCF� VCF patients are 2-3xs more likely to die of pulmonary

causes� Most common cause of death was pulmonary

disease, including COPD and pneumonia

Kado et al., Arch Intern Med 1999

Initially unrecognized VCFs on Chest X-ray

32

934 women age 60 and older, hospitalized for various reasonsChest x-rays reviewed for fracture

Gehlbach SH et al, Osteoporos Int, 2000;11:577-582

020406080

100120140

Fractures Mentioned inRadiologist’s Report

52%

Mentioned inDischargeSummary

23%

Mentioned in Record

Osteoporosis

17%

Treatment forOsteoporosis

7%Numb

er of

subje

cts

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Clinical Management Goals� Identify when a pt has a VCF� Etiology:� Other Processes?� Osteoporosis?

� Define fracture configuration � Develop multidisciplinary

treatment plan� Heal this fracture� RESUME MOBILITY� Prevent the next fracture

Work up�History and Physical Exam�Labs�Imaging: � Plain Radiographs (correlate with painful

level, presence of other fxs? review prior films if available)� MRI� CT Scan � Bone Scan� DXA/VFA

HISTORY AND PHYSICAL EXAMHistory:PAIN?� Recent event?� No Trauma does not exclude OP fx� Trauma does not exclude OP fx� Is the pain different than baseline back pain?� Fx Hx� Prior Bone wu/rx?� Prior Level of Fct in Hx� Fall historyPHYSICAL EXAM: � HEIGHT, � Tap Test� Trunk mobility� SL stance: balance and pelvic sx

Basic Metabolic Bone Labs� CBC with diff� Comprehensive metabolic panel� To include Ca, Mag, Phos, Alk phos, albumin

� Vit D 25 OH� Intact PTH� TSH, Free T4� PTH� Bone turnover markers – not consistent� Bone resorption - Urine NTX or serum CTX or uri CTX � Bone formation - Bone-specific alkaline phosphatase or osteocalcin(Use 1 marker or 1 resorption and 1 formation marker.)

� Bone Biopsy – not routinely used except in atypical presentations without clear diagnosis or in patients with ROD to establish the presence of adynamic bone.

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X-RAYIdeal is AP and Lateral x-ray

Parallel to endplate

Use comparison films to assess progression

Use cone down or centered AP & Lat views if needed

May also need to compare prior CXRs

Not all VCFs are Osteoporotic FracturesMay need MRI, CT or Bone Scan

Multiple MyelomaMetastasis OsteoporoticFracture

DXA

T SCORENormal -1 and above

Low bone mass -1 to -2.5

Osteoporosis < -2.5

Established osteoporosis

< -2.5 and one or more fractures

DXA/VFA� DXA Based vertebral Fracture Analysis

� Knowing a patient has already had a fracture will affect:

- patient risk for subsequent fracture(predictive of future fx risk, indep of BMD)

- treatment decision making (provider & patient)� Should be added to DXA studies of VCF pts, or all

DXA patients over 50

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Vertebral fractures semi-quantitative grading

41

Normal

Anterior Middle Mild fracture

MiddleModerate fracture

MiddleSevere fracture

Anterior

Anterior

Posterior

Posterior

Posterior

Genant HK & Jergas M, Osteoporos Int, 1993;14 (suppl 3):S43-55

Grade0

1

2

3

Treatment: Non Operative� Treatment Protocol

– Bed rest– Narcotic analgesics– Braces– Modalities for symptomatic relief– PT for fall assessment, mobility trg, d/c disposition, HEP– Prevent the next fracture!

Include in treatment plan how to identify and treat underlying bone disorder

Conservative management of patients with an osteoporotic vertebral fracture: a review of the

literature.Sources of data : PubMed, Medline, Cochrane, CINAHL and Embase

databases using various combinations of the keywords ‘osteoporosis’, ‘vertebral compression fractures’, ‘brace’, ‘bracing’, ‘orthosis’, ‘conservative management’ and ‘rehabilitation’ over the years 1966 –2011. Paucity of RCTs.

Summary: Conservative management of VCF has not been standardized. Forms of conservative treatment commonly used in these patients include bed

rest, analgesic medication, physiotherapy and bracing. Reviewed the best evidence available on the conservative care of patients with

osteoporotic VCFs and associated back pain, focusing on the role of the most commonly used spinal orthoses.

*Until the best conservative management for patients with VCFs is defined and standardized, no conclusions can be drawn on the superiority or otherwise of vertebral augmentaion techniques over conservative management.

J Bone Joint Surg Br 2012 Feb;94(2):152-7.Longo UG, Loppini M, Denaro L, Maffulli N, Denaro V Need MORE + better studies

VCF Operative Treatment OptionsVertebral Augmentation� Designed to stabilize painful VCFs� Debate between best method� Each has reported complications and beneficial

series� Is there a benefit to restoring height, correcting

kyphotic deformity and not putting cement in under pressure

� Is there a benefit to vertebral augmentation over pharmacologic treatment for quicker relief of symptoms and earlier mobilization

� DEBATE EXPANDED as to INDICATIONS

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Physical Therapy�Safe Mobility �Fall prevention strategies�Balance and

Proprioprioception� training�Limb, core, targeted back

strengthening techniques

VCF TreatmentRest: Compounds problems of bone

loss, muscle and balance loss– Prolonged symptoms

– decreased mobility, increased dependence, narcotic use

– Exacerbates bone loss and muscle wasting–loss up to 2% per week reported after prolonged bed rest1 1 Johnell et al., Osteoporosis Int 2000

– Further deformity may contribute to further problems– Poor appetite, increased fall risk, mech load on ant

column

Pharmacological agents for treatment of osteoporosis

Effective therapies are available and includeCa, Vit D

Anitresorptives – Bisphosphonates, RankL inhibitorAnabolic – TeraparatideCalcitonin, Strontium, Raloxifine, HRT

� Can reduce vertebral, hip and other fractures by 30% to 65%

Nutrition Summary:Daily Calcium and Vitamin DWomen� < 50 yo: 1,000 milligrams (mg) of calcium* � 400 - 800 international units (IUs) of vitamin D every day.

� Age 50 and older: 1,200 mg of calcium*� 800-1,000 international units (IUs) of vitamin D every day.

Men� < 50yo: 1,000 milligrams (mg) of calcium* � 400-800 IUs of vitamin D every day.

� Age 50-70: 1,000 mg of calcium* and� 800-1,000 IUs of vitamin D every day.

� Age 71 and older: 1,200 mg of calcium* � 800-1,000 IUs of vitamin D every day.

*This includes the total amount of calcium you get from both food and supplements. Daily Calcium Recommendations� Titrate Vit D 25OH 40-100 ng/ml

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Pharmacological agents for treatment of osteoporosis

Effective therapies are widely available and

can reduce vertebral, hip and other fractures

by 30% to 65%, even in patients who have already

suffered a fracture

Bisphosphonates� Alendronate (FOSAMAX®)� Risedronate (ACTONEL®)� Ibandronate (BONVIVA®)� Zolendronate (ACLASTA®)� Denosumab

Pharmacological agents shown to reduce fracture risk

SERMs• Raloxifene (EVISTA®)

ANABOLICSStimulators of bone formation• rh-PTH (FORTEO®)

Mixed mode of action• Strontium ranelate

(PROTELOS®)Hormone therapy• Estrogen / progestin

Anti-fracture efficacy of the most frequently used treatments for postmenopausal osteoporosis

As derived from placebo controlled randomized trials

51

Drug Vertebral fractures Non-vertebral fractures (hip)

Alendronate + + + + +Calcitonin (nasal) + 0Etidronate + 0HRT + + +PTH + + + + +Raloxifene + + + 0Risedronate + + + + +Strontium ranelate + + + +

Adapted from Delmas PD, Lancet, 2002;359:2018-2026

Denosmab and VCF trials: showed a decrease in fracture rates comparable to those achieved with zoledronic acid and teriparatide

Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of

randomized, controlled trials.Abstract• Purpose: assess the effects of calcitonin versus placebo for the treatment of acute pain in patients sustaining stable, recent, osteoporotic vertebral compression fractures. •Source: MEDLINE (1966-2003), EMBASE (1980-2003), Cochrane Controlled Trial Registry (2003, volume 3), other databases, and conference proceedings. • Combined results from five randomized controlled trials, involving 246 patients, determined that calcitonin significantly reduced the severity of pain using a visual analogue scale following diagnosis. •Pain at rest: reduced as early as 1 week into treatment and this effect continued weekly to 4 weeks). Benefits also seen with sitting, standing, walking.• Side effects were gastrointestinal, minor and often self-limited. •Conclusions: Calcitonin appears to be effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilization.

Knopp, et al. Osteop Intl 2005 Oct;16(10):1281-90. Epub 2004 Dec 22.

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Calcitonin update: Mar 5, 2013� (Reuters) - A panel of advisers to the Food and Drug Administration

recommended on Tuesday that the agency no longer support the marketing of calcitonin salmon as a treatment for osteoporosis in post-menopausal women.� The panel voted 12-9 that the benefit of calcitonin salmon products in

treating bone-thinning associated with osteoporosis is outweighed by a potential increase in the risk of cancer.� Last July, European regulators recommended that long-term use of

calcitonin be curtailed after a review found evidence of a small increased risk of cancer with long-term use of the drugs.� They ruled that the benefits of calcitonin-containing medicines

did not outweigh their risks in the treatment of osteoporosis and that they should no longer be used for this condition.� They recommended that the drugs should only be authorized for short-

term use in Paget's disease, a bone disorder; for acute bone loss due to sudden immobilization; and for excess calcium in the blood caused by cancer.

PTH effects on risk of new vertebral fractures over 18 months

54

Risk

redu

ction

(RR)

Placebo(n=448) rhPTH 20(n=444)

64 22100%

75%50%

0%25%

% of

wome

n

8

0246

101214

RR 0.35

65%

N patients with 1 or more fractures1 5 10

1520

25 30

Ser Val Ser Glu Ile Gln Leu Met His Asn

Leu

Gly

LysHisLeuAsnSerMetGluArgValGlu

Trp

Leu

Arg Lys Lys Leu Gln Asp Val His Asn Phe

Placebo PTH 20 µgNeer RM et al, N Engl J Med, 2001;344:1434-1441

Pharmacologics for Acute Care� Starting to see anti-resorptives and anabolic bone

agents being used in the acute care of fragility fractures.

�When is it ok to start them?�Which ones will help or hinder the acute fx healing

process?� How long to keep them on? � Indications?� Augment surgical care with Pharmacologics

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IF 50+ and back pain, think VCF!Identify, evaluate and treat the underlying cause of the fracture or back

pain.Document: low bone mass, osteoporosis, fragility fracture and initiate

evaluation and referralCall a VCF when you see it, even if not acute. (inc risk for subs fx)Consider assoc fractures (pelvic, sacral insufficiency fxs, atypical fem fx -

BPs)Establish referral mechanisms for Bone Health Specialists, DXA,

Metabolic Bone Panel at your facility. MAKE IT EASY so you do it. In all spine patients over 50 – Consider screening with FRAX (or

similar), DXA, Vit D, AVS with education with reminder to discuss this with PMD.

PREVENT THE NEXT FRACTURE!

Start Now:� For every patient 50+ include Bone Health� Ask: Who is taking care of your bones? FX Hx? OP dx /treatment?� HEIGHT � Measure Ca & Vit D and treat!� Frax risk assessment� Metabolic Bone Panel� Educate Patient� Establish follow up, inform PMD

� RESOURCES: � Tools: � Check lists, order sets� Own the Bone

� Educational materials in office � Provider and patient� NOF, IOF, ASBMR, AAOS

� Local: ABH/FORE

UCSFSKELETAL HEALTH SERVICE

Bone Health across the lifespan…Pediatric to Geriatric

Orthopaedic Institute Mission Bay

skeletalhealth@ucsf.edu

Who wants their next fracture prevented?

Who wants their next fracture prevented?

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THANK YOU Fx 50+� ORDERS: � 1. Labs: Metabolic Bone Screen - CBC, Comp Met Panel (include Alk Phos, Ca, phos, creatinine, LFTs, albumin), TSH, free T4, intact PTH, 25(OH)Vit D� 2. Nutritional supplements: Ca and Vit D: 1000 IU vitamin D3 (cholecalciferol) per day and 1250 mg Ca carbonate (500 mg elemental Ca per tablet) twice a day. � Once 25 OH Vit D level is available (if > 30 ng/ml, continue 1000 IU cholecalciferol/day; if 20-30 ng/ml give 2000 IU cholecalciferol/day; if < 20 ng/ml give 50,000 IU ergocalciferol immediately and then twice weekly for 4 weeks and re-measure level). � 3. Spine xrays if - Ht loss .1.5 cm over past 2 yrs, hx of increasing kyphosis, � 4. PT: “for safe mobility, fall risk screening and fall prevention instruction” � 5. Education about Bone Health (include: patient/family informed of increased risk for subsequent fractures) - designated person to be identified (PA, NP, PT, RN, other?)� 6. DC orders: DXA Scan (post discharge) if not done in past 2 yrs, continue Ca/vit D supplements, F/U with PMD, Referral to Endocrine/Renal if needed

NUTRITION POSITIVE BONE EFFECTS:

• CALCIUM

• VIT D

•VIT A *

• PROTEIN

• ADEQUATE CALORIES

NEGATIVE BONE EFFECTS:

• SODIUM

• Soft Drinks (Phos, displaces intake of healthy stuff)

• CALORIC RESTRICTION

•CAFFIENE, TOBACCO

Adult Bone Improves with ExerciseWalking briskly, running and strength training have

shown to mildly increase or attenuate bone loss AND decrease fracture risk.

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Every Fracture is an Opportunity

Regardless of Mechanism of Injury or Age or Gender

Mair suggests thatjī in wēijī is closer to "crucial point" than to "opportunity."

Thank you!

Aenor.sawyer@ucsf.edu