Taking on the challenge of publishing an International Magazine of Shockwave Therapy

is justified by the great progress in clinicalresearch and results that have been madeknown in several scientific publications and ininternational conferences. Many researchershave dedicated themselves to the developmentof this technology all around the world. TheInternational Society for MusculoskeletalShockwave Therapy, founded in 1997 andheadquartered in Wien, was an importantlandmark and was made possible thanks tothe extraordinary efforts of researchersDr. Wolfgang Schaden and Richard Thiele.Many others could be mentioned but I'd like toremember Dr. Chen Jin Wang, whose work canhelp us find answers to many importantquestions and whose research will play anessential role in this publication.

This publication is open to doctors,veterinarians and physicists who wish topublish their findings in this field. Initially,our projection is for three annual editions.

On behalf of the ISMST, we thank Merck Sharp& Dohme do Brazil for their support whichmade this publication possible. Finally, wehope to contribute effectively to thedevelopment and to increasing awarenessabout the Extracorporal Shockwave Therapy.

Paulo Roberto Dias dos Santos

O desafio de iniciarmos a publicação de umaRevista Internacional de Ondas de Choque éplenamente justificada pelo grande avanço naspesquisas e nos resultados clínicos alcançados,divulgados em várias publicações científicas eem Congressos Internacionais. Váriospesquisadores têm nos últimos anos sededicado de forma expressiva aodesenvolvimento desta tecnologia no mundo.A International Society for MusculoskeletalShockwave Therapy- ISMST fundada em1997 com sede em Viena - Áustria foi ummarco importante na consolidação desta,graças ao trabalho incansável dospesquisadores Dr. Wolfgang Schaden eRichard Thiele, que são responsáveis por boaparte do sucesso alcançado. Muitos outrospoderiam ser citados ,cada um com suaimportância, mas um em especial deve serlembrado o Dr. Chen Jin Wang que temrespondido através de seus trabalhos muitasquestões importantes e certamente terápapel fundamental nesta publicação.

Esta publicação é aberta a médicos,veterinários, físicos e pesquisadores quequeiram divulgar seus trabalhos nesta área.Inicialmente estão previstas três edições anuais.

Em nome da ISMST agradecemos o apoiodado pela empresa Merck Sharp & Dohmedo Brasil sem a qual não seria possível arealização desta.

Finalmente, esperamos contribuir de formaefetiva para o desenvolvimento e divulgação daTerapia por Ondas de Choque Extracorpórea.

Editorial · Editor‘s Note

Editor’s Note .......................................................... 1President’s Message............................................. 18th International Congress of the ISMST........ 2Biological Mechanism ofMusculoskeletal Shockwaves............................ 5Effects of Extracorporeal ShockwaveTreatment on equine tendon healing........... 12Instructions for Authors ................................... 15

It is a great pleasurefor me to welcome youall as members of ourSociety at the firstNewsletter of ISMSTin 2005.

Since 1997 when ISMST was founded inVienna, the development of extracorporealshock wave therapy has grown with recentscientific findings and clinical studies in spiteof the initial scepticism in the orthopedicssurgeons community. A small group ofpioneers has become a renowned internationalsociety with more than 492 members of53 countries and, in the last Annual GeneralMeeting of the ISMST on May 30th 2005,81 new members from 32 countries wereaccepted.

In all ISMST's meetings that I have been

participated, we have discussed about morepossibilities to divulgate the Shock WaveTherapy in our countries to find a generalmedical interest and to keep the minds opento discuss about the understanding, theefficacy and security of this method.

I really think that a Newsletter is a goodidea and an excellent way to share scientificknowledge and the latest news aboutextracorporeal shock wave therapy.

I hope you will be active participants thereforeyou will cultivate the spirit of internationalexchange of ideas, a very healthy habit of this“shockwave family”.

Congratulations!

I am looking forward to seeing you all in Riode Janeiro for the ISMST Congress in 2006.

Ana Claudia Souza - ISMST President

President’s Message

Inside this Issue

Chief Editor• Paulo Roberto Dias dos Santos, MD

(Brazil) - prds@uol.com.br

Associate Editor• Ching-Jen Wang, MD (Taiwan)

w281211@adm.cgmh.org.tw

Editorial Board• Ana Claudia Souza, MD (Brazil)

anaclaudia@cortrel.com.br• Carlos Leal, MD (Columbia)

leal@owc.com.co• Heinz Kuderna, MD (Áustria)

kuderna-unfallchir.wien@aon.ato• Kimberly Eickmeier, MD (USA)

Keickmeier@christieclinic.com• Leonardo Jaime Guiloff Waissbluth,

MD (Chile) - lguiloff@davila.ch• Ludger Gerdsmeyer, MD (Germany)

gerdesmeyer@aol.com• Matthias Buch, MD (Germany)

matthiasbuch@aol.com• Paulo Roberto Rockett, MD (Brazil)

rockett@vant.com.br• Richard Levitt, MD (USA)

falevitt@aol.com• Richard Thiele, MD (Germany)

harthi@t-online.de• Robert Gordon, MD (Canada)

gordon@skockwavedoc.com • Sergio Russo, MD (Italy)

serghiey@hotmail.com• Vinzenz Auersperg, MD (Áustria)

Vinzenz.Auersperg@akh.linz.at• Weil Lowel Jr, MD (USA)

lweiljr@weil4feet.com• Wolfgang Schaden, MD (Austria)

med.eswt.schaden@aon.at

Veterinary Committee • Scott Mc Clure, DVM (USA)

mcclures@iastate.edu• Ana Liz Garcia Alves, DVM (Brazil)

anaalves@fmvz.unesp.br• Ana Cristina Bassit, DVM (Brazil)

anafbassit@uol.com.br

Editorial Office Avenida Pacaembu,1024CEP 01234-000 - São Paulo - Brazil Fone: 55-11-3825·8699E mail : prds@uol.com.br

website: www.ismst.com

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The International Society forMusculoskeletal Shockwave Therapy(ISMST) has been founded 1997 inVienna, the development has beenfast and the society now has about500 members from 53 countriesfrom all over the world. The 8thannual congress this year with250 participants was held at theVienna Marriott Hotel, 85 papershave been presented form 20 differentcountries.

The scientific level of thepresentations has been high andshowed the efficacy of ESWT(extracorporeal shock wave therapy)of the well introduced indications asthere are the plantar heel pain, thetennis elbow, the calcifying tendonitisof the rotator cuff and delayed bonehealing or pseudarthrosis. Like inTaiwan last year there have been mostinteresting publications about basicresearch. Additional we hadpresentations about study design andabout the different special featuresat the different countries concerningreimbursement and logisticalpeculiarities.

The highlights of the congress:During the last years we had a lot

of controversial discussions about high

level studies with randomized, blindedand controlled design showingcontradictory results. Some of thepresented studies at that congresshelped us to understand the reasonsfor these contradictions. On theone hand we got clarity into thediscussions because of the findings ofthe basic research; on the other handwe got results of new studies showingpossible bias of the conflictingstatements. For example there areseveral studies showing, that localanaesthesia has a negative influenceon the outcome of especially lowenergy shock wave therapy (Jan-DirkRompe, Germany; Gerold Labek,Austria).

The results of basic research of thelast years changed our thinking aboutthe effects on the treated tissue, theyall show changes of the molecularbiological structures and enzymaticeffects. Shock waves with an energylevel used in medicine seldom causemechanical breakages or ruptures ofthe tissue. Astonishing is anobservation of Wolfgang Schaden athis retrospective investigations of theresults of the shock wave treatmentsof delayed bone healing andpseudarthrosis at the Meidlinger

Unfall Krankenhaus in Vienna, hefound at several indications betterresults using less energy and/or lessimpulses (his over all success rate isabout 80% healing after ESWT).

These clinical findings areconfirmed by a lot of publications:Markus Maier (Germany) showed inhis trials with rats, that osteoneogenesisis possible without mechanicaldestructions of the tissue and bonerespectively. The working groupsaround Ching-Jen Wang (Taiwan),Sergio Russo (Italy), Helmut Neuland(Germany) and Ludger Gerdesmeyer(Germany) showed impressively theincrease of enzymes in the treatedtissue, for example VEGF (vesselendothelial growth factor), BMP(bone morphogenetic protein), OP(osteogenetic protein), NO (Nitrideoxide) und other enzymes have beenproven. There are reasonable doubts onthe mechanical hypothesis of shockwave mechanisms, as we discussed15 years ago, thinking that microlesions (like ruptures and breakages ofthe bone or the soft tissue in the focus)caused by ESWT induce healing. Themain message of the congress was theunderstanding, that ESWT does notcause mechanical effects, it causes amicrobiological effect, we could say, itcauses healing by bioengineering.

A very interesting effect has beenfound by Ludger Gerdesmeyer(Germany), he demonstrated theantibacterial effect of shock waves,especially at bacteria likeStaphylococcus aureus, MRSA.

There has been taken note of newreports about clinical studies accordinghealing after shock wave therapy onosteochondral lesions, particularly thepapers of Helmut Neuland (Germany),Hideshige Moryia (Chiba/Japan) andRichard Thiele (Berlin) have beendiscussed extensively due to the

8th International Congress of the ISMSTInternational Society for MusculoskeletalShockwave TherapyMay 29th - June 1st, 2005

Vinzenz Auersperg1,Wolfgang Schaden

impressive success of that treatment.An international press conference

held on May 31st, 2005 at theconference venue had good response.Otto Hess (cardiologic professorat the Inselspital Bern, Switzerland)presented the results of hisinvestigations regardingrevascularisation of ischemicmyocardium thru shock wavetherapy, Hildegunde Piza-Katzer(surgeon in chief and professorat the dept. of plastic surgery of theInnsbruck University Clinic, Austria)showed astonishing results of shockwave therapy after burning lesions ofhumeral skin and of a randomizedanimal trial regarding ischemic skinlesions and shock wave therapy andWolfgang Schaden (traumatologist atthe Meidlinger Trauma Center Wien,Austria) demonstrated the results of apilot study concerning shock wavetherapy and skin ulcers of differentreasons (diabetic ulcers, posttraumaticdelayed skin healing etc.). There havebeen reports in the daily news at thenational broadcast channel and in thenews papers and reports at thescientific programmes.

As at the last ISMST congresseswe could organize sessions withveterinarian papers, mainly USAmerican studies with horses havebeen presented. Shock wave therapyin that field is obviously increasing.It is one of the advantages of theISMST as a society, that we held itopen for everyone who is interestedin shock waves, so we have a mixedcomposition of members of all fieldsof application - physicians from alldifferent disciplines, veterinarians,clinical investigators, basicresearchers, manufacturers anddistributors. The scientific levelof the presented papers has risenover the years.

The 8th ISMST Congress hasbeen held together with the5th meeting of the Germanspeaking shock wave societies(5. Dreiländertreffen derÖsterreichischen, Schweizerischenund Deutschen Gesellschaften fürExtrakorporale Stoßwellentherapie).The most important society in thatgroup is the DIGEST(Deutschsprachige InternationaleGesellschaft für Extrakorporale

Stoßwellentherapie), and this societyprovided an award for the best paperregarding shock wave therapy.The last years the first two awardshave been presented to Markus Maierand Ludger Gerdesmeyer. This year itwas a big honour for the ISMST, thatthe ceremony of awarding has takenplace at the opening ceremony of theISMST congress and it was presentedto Jan-Dirk Rompe (Germany) for hisclinical study about differences inoutcome of ESWT regardingtreatment with or without localanaesthetics. At the DIGESTmember's meeting in Vienna theassembly has voted for calling forparticipants for that DIGEST awardalso thru the ISMST correspondence.This is a sign for good relationsbetween the societies and we hopevery much to keep the contact asclose as it is now.

Besides the scientific programmethe social events have been of goodacceptance. special guests have beeninvited for a presidential dinner tocelebrate the 8th birthday of theISMST founded 1997 in Vienna. Areception at the city hall of Vienna asan invitation of the Lord Mayor ofVienna took place on Monday, May30th, 2005. The next day wecelebrated the society evening in bestmood, beginning the event with astreet car drive to a typical Viennesewinery (25 minutes walk after thestreet car drive thru the city, than amagnificent view over Vienna,Viennese winery atmosphere withtypical music and wine and food andlots of scientific discussions, friendlytalks and singing and laughing!). Thewhole meeting was characterized bythe excellent communication, which isthe main interest of the ISMST. So asorganizers we are happy that thecongress was a big success.

We are convinced that this societyis growing and we will get membersof other disciplines, we are alreadydiscussing the name of the societybecause of the new fields of shockwave therapy which are not onlymusculoskeletal. The developmentwill continue! We are very muchlooking forward to the next meeting,the 9th ISMST Congress in Rio deJaneiro from April 20th to April 23rd,2006 (www.ismst.com).

CORRESPONDING ADDRESS:

Dr. Vinzenz AuerspergOrthopaedic Department of theGeneral Hospital Linz (AKH Linz)Krankenhausstrasse 9A-4020 LinzAustria - Europevinzenz.auersperg@akh.linz.ator vinzenz@auersperg.cc

Dinner party. Groups from Brazil and Twain andDr Richard Thiele.

Ana Claudia Souza and Wolfgang Schaden.

4 5

AbstractThese studies were conducted to

investigate the biological mechanismof musculoskeletal shockwaves. Theinvestigations were independentlyperformed in tendon and bone, andat the tendon-bone interface inrabbits. The study limbs were treatedwith shockwaves, whereas the controllimbs received sham treatment with noshockwave. The evaluations includedhistomorphological examination,biomechanical analysis and immuno-histochemical assessments of angiogenic growth indicators includingendothelial nitric oxide synthase(eNOS), vessel endothelial growthfactor (VEGF), bone morphologicalprotein (BMP-2) and proliferating cellnuclear antigen (PCNA).

The results showed higher bonestrength and bone mass, and bettertensile strength of the graft attendon-bone interface in theshockwave group than the controlgroup. Furthermore, shockwavetreatment significantly induced theingrowth of neovascularizationassociated with increased expressionsof angiogenic growth indicators intendon and bone, and at the tendon-bone interface as compared with thecontrol. The effects of shock wavesappeared to be time-dependent aswell as being dose-dependent.

In conclusion, extracorporealshock waves produced consistentbiological effects in tendon and bone,and at the tendon-bone interface.The biological mechanism ofmusculoskeletal shockwaves appearedto stimulate the expressions ofangiogenic growth factors and inducethe ingrowth of neovascularization.Neovascularization may play a role inthe improvement of blood supply andhealing of tendon and bone.

IntroductionExtracorporeal shock wave has

been shown to be effective for certainorthopedic conditions includingnon-union of long bone fracture,1,2,3,4

calcifying tendonitis of theshoulder,5,6,7,8,9 lateral epicondylitis ofthe elbow,10,11,12,13 proximal plantarfasciitis14,15,16 and Achilles tendonitis.17

In animal experiments, shockwavesalso showed positive effects in pro-moting bone healing.18,19,20,21 However,the exact mechanism of shockwavein musculoskeletal disorders remainsunknown. The results of animalexperiments demonstrated thatshockwaves induced neovasculariza-tion at the tendon-bone junction.22,23

We hypothesized that physicalshockwaves might induce biologicaleffects that lead to healing of tendonsand bone. The purposes of the studieswere to investigate the biologicaleffects of shockwaves in tendon,bone and tendon-bone interface andto elucidate the biological mechanismof musculoskeletal shockwaves.

Materials and Methods The approval of The Institutional

Review Board was obtained. Thesestudies were performed under theguidelines and the care and use ofanimals in research.

I. Experimental study in tendonFifty New Zealand white rabbits

of 12 months old with body weightranging from 2.5 to 3.5 Kg were usedin this study. The right limbs (studyside) received shockwave treatmentto the Achilles tendon near theinsertion to heel bone, while the leftlimbs (control side) received shamtreatment with no shock waves.The source of shockwave was froman electrohydraulic OssaTron device(High Medical Technology,Kreuzlingen, Switzerland). Theshockwave tube was focused on theAchilles tendon near the insertion,and the depth of the treatment wasdetermined with the control guide ofthe machine and confirmed withC-arm image. Each of the study limbsreceived a single treatment ofshockwave with 500 impulses at14 kV (equivalent to 0.18 mJ/mm2).

The shockwave dosage so selectedwas based on our previous experi-ences in animal studies.21,22,23 Thesham treatment was performed onthe left limbs (control side) using adummy electrode that did not generateacoustic waves with the impulses. Histomorphological examination

Biopsies of the Achilles tendon-bone unit were performed in 0, 1, 4, 8and 12 weeks with 10 rabbits at eachtime interval with the first biopsyobtained in 24 hours after shockwaveapplication. The decalcifiedspecimens were sectioned andstained with hematoxylin-eosin stain.The tissue distributions and thenumber of new blood vesselsincluding capillary and muscularizedvessel were examined microscopically.Immunohistochemistry analysis

The angiogenic growth markersincluding vessel endothelial growthfactor (VEGF) and endothelial nitricoxide synthase (eNOS) wereexamined to confirm the neovascular-ization, and proliferating cell nuclearantigen (PCNA) was chosen to reflectendothelial cell proliferation withimmunohistochemistry stains.24,25,26

The vessels showing positive VEGFexpression and cells displayingpositive PCNA and eNOS expressionswere counted microscopically andthe numbers of cells and tissueswith positive expression werequantitatively assessed.Results of biological response intendon

The results of eNOS, VEGF andPCNA expressions and the numberof neo-vessel of the study and thecontrol sides are summarized inTable 1. In the study side, asignificant increase in the number ofneo-vessels was noted in 4 to 12weeks, whereas no increase ofneo-vessels was noted in the controlside, and the difference wasstatistically significant. It appearedthat the ingrowth of neo-vessels aftershockwave treatment was timedependent. In the study side,significant increases of eNOS, VEGFand PCNA were noted in as early asone week and lasted for 8 weeksbefore they declined to normal at12 weeks, except PCNA increaselasted until 12 weeks (Fig. 1). In thecontrol side, however, no significantchanges in eNOS, VEGF and PCNAexpressions were noted, and thedifferences between the study andcontrol sides were statistically

Biological Mechanism of Musculoskeletal ShockwavesChing-Jen Wang, MD1, Feng-Sheng Wang,PhD2 and Kuender D. Yang, MD, PhD2

The Department of Orthopedic Surgery1 andMedical Research2 Chang Gung Memorial Hospitalat Kaohsiung Taiwan.

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Histomorphologicalexamination

After biomechanicaltesting, the specimens weredecalcified and sectioned andsubject to hematoxylin-eosin,alcian blue or alizarin redstains (Sigma Chemicals Inc,St. Louis, MO, USA) for thepurpose of distinguishingfibrous tissue, cartilaginousand bony tissues within theregion of interest. Immunohistochemicalexamination

The angiogenic activitiesincluding eNOS, VEGF,BMP-2 and PCNA wereexamined with immunohisto-chemistry stains forverification of neo-vessels.The specimens wereimmunostained for eNOS,VEGF, BMP-2 and PCNA(Santa Cruz Biotechnolog Inc,CA, USA). An antibody againstvon Willebrand factor (vWF)was used to identify theimmunolocalization ofneo-vessels in the fracturesites. The number of positiveimmuno-labeled cells and totalcells in each area werecounted and the percentage ofpositive labeled cells wascalculated. Results of biological response in bone

The histomorphological features showed thathigh-energy shock waves produced significantlymore cortical bone, less fibrous tissue andcomparable woven bone than the control andlow-energy shock waves (Fig. 2). The results oflow-energy shock wave did not differ significantlyfrom the control group.

The results of biomechanical study showed thathigh-energy shock waves demonstrated better bonestrength including peak load, peak stress andmodulus of elasticity than low-energy shock waveand the control (Fig. 3). The low-energy shockwaves showed comparable results as compared withthe control.

The results of positive eNOS, BMP-2, VEGF andPCNA immunostained cells and the numbers ofneo-vessels in the fracture sites of the control,low- and high-energy groups are summarized inTable 2. The numbers of neo-vessels and cells withpositive eNOS, BMP-2, VEGF and PCNA expressionsare significantly higher in high-energy shockwavegroup than the control and low-energy groups(Fig. 4). The data of the low-energy group didnot differ significantly from the control group.The biological effects of shockwaves appeared tobe dose-dependent.

Fig 1a e-NOsFig. 1b VEGF Fig. 1c PCNA

Tendon

Bone

(Control)

Tendon

Bone

(Shock Wave)

Tendon

Bone

(Control)

Tendon

Bone

(Shock Wave)

Tendon

Bone

(Control)

Tendon

Bone

(Shock Wave)

Fig. 1

significant. It appeared that shockwaves stimulated theearly release of eNOS, VEGF and PCNA expressions, andsubsequent ingrowth of neo-vessels.

II. Experimental study in boneTwenty-four New Zealand white rabbits of 12 months old

with body weight ranging from 2.7 kg to 3.6 kg were used inthis study. A 1.5 mm Kirchnur pin was inserted retrogradeinto the canal of the femur through a mini-arthrotomy ofthe knee. A closed fracture of the right femur was createdwith a three-point bend method and was confirmed withradiographs. The rabbits were randomly divided into threegroups with eight rabbits in each group. The first group(the control) received sham treatment with no shock wave.The second group received low-energy shock wave with2000 impulses at 14 kV (equivalent to 0.18 mJ/mm2 energyflux density). The third group received high-energy shockwave with 4000 impulses at 14 KV. Shock waves wereapplied in one week after the operation when the surgicalwounds had healed. The location of the fracture site andthe depth of the treatment were confirmed with the controlguide of the machine and C-arm imaging. The shamtreatment was performed with a dummy electrode that didnot generate acoustic waves with the impulses.

Radiographs of the right femur in A-P and lateral viewswere performed in1,4,8 and 12 weeks. The fracture healingwas evaluated with clinical assessment and confirmed withradiographic examination.Biomechanical examination

The animals were sacrificed at 12 weeks, and a5-cm long femur bone including the callus was harvested.The specimens were subject to biomechanical testing onMaterial Testing System (MTS, Minneapolis, MN) includingpeak load, peak stress and modulus of elasticity. Thebiomechanical testing was similarly performed inhigh-energy, low-energy and control groups.

Time Control Shockwave P-value

(N=50) (N=50)Mean ± SD Mean ± SD

0- week (N=10)eNOS 112 ± 19 104 ± 21 0.57VEGF 14 ± 3 12 ± 4 0.94PCNA 145 ± 21 132 ± 24 0.75Neo-vessel 22 ± 3 24 ± 4 0.93

1-week (N=10)eNOS 124 ± 21 293 ± 31

9

eNOS

Shockwave Control

BMP-2

VEGF-A

Fig. 7

III. Experimental study intendon-bone interface

Thirty-six New Zealand whiterabbits of 12 months old with bodyweight ranging from 2.79 Kg to 3.65 Kgwere used in this study. Arthrotomy ofthe knee was carried out and theanterior cruciate ligament (ACL) wasexcised. The long digital extensortendon was dissected off distally at themusculotendinous junction while the

proximal end was left intact. A tibiatunnel was created with a graftsize-matched drill bit. The distal end ofthe graft was pulled through the tibiatunnel to complete ACL reconstruction.Shockwave application

The left knees received shamtreatment with no shock wave, andwere used as the control group.The right knees received shockwavetreatment immediately after surgery,

and were regarded as the study group.The shockwave tube was focused onthe mid-portion of the tibia tunnel withthe control guide of the device, and thedepth was estimated clinically anddetermined with an ultrasound guide.Each knee was treated with 500impulses of shockwaves at 14 kV(equivalent to 0.18 mJ/mm2) to theright knee. In sham treatment, adummy electrode was used that noacoustic waves were generated withthe impulses. Histomorphological Studies

Twenty-four rabbits were sacrificedat different time intervals with4 rabbits each at 1, 2, 4, 8, 12 and24 weeks. The central portion of theproximal tibia including the tendongraft was harvested. The specimenswere decalcified, sectioned andstained with hematoxylin-eosin stain.The distributions of the tissuessurrounding tendon graft and thebonding of trabecular bone to tendonwere examined microscopically.Biomechanical examination

Twelve rabbits were sacrificed at12 and 24 weeks with 6 rabbits at eachtime interval. The ligament structuresof the knee were removed and onlythe ACL graft was retained. Thetensile strength of the graft wasmeasured with slow load distractioncurve on Material Testing Machine(MTS, Minneapolis, MN). The pulloutstrength, the failure load and themodes of failure were analyzed. Immunohistochemical examination

The decalcified specimens werecut into sections in longitudinal andaxial directions. Sections wereimmunostained for eNOS, VEGF,BMP-2 and PCNA (Santa CruzBiotechnolog Inc, CA, USA) for thepurpose of identifying angiogenicgrowth indicators. An antibody againstvon Willebrand factor (vWF) was usedto identify the immunolocalization ofneo-vessels. The numbers withpositive expression were quantitativelyassessed.Results of biological response intendon-bone interface

The trabecular bone in thesurrounding tissues of the tendon graftincreased significantly with time in thestudy group (P < 0.05), whereas, thechanges in the control group werestatistically not significant (P > 0.05).The difference in the amount oftrabecular bone around the tendongraft between the study and controlgroups was statistically significant

vWF

eNOS

PCNA

BMP-2

VEGF

Fig. 4

Shock wave

Tn

A B

C D

CgTb

Tn

Fs

Tb

ControlFig. 5

The numbers of neo-vessels and cells with positive eNOS, BMP-2, VEGF and PCNA expressions aresignificantly higher in high-energy shock wave group than the control group.

The trabecular bone surrounding the tendon graft increased significantly in the shock wave group ascompared with the control group. The bonding between tendon and bone was much more intimatein the study group than the control.37

8

after 4 weeks. The bonding between tendonand bone was much more intimate in thestudy group than the control group, andthe difference in the percentage of bondingbetween tendon and bone was statisticallysignificant between the study and controlgroups (P < 0.05) (Fig. 5).

The biomechanical testing showed thathigher tensile strength of the graft andbetter pullout failure load noted in theshockwave group than the control group(Fig. 6).

The results of eNOS, VEGF, PCNA andBMP-2 expressions and the number ofneo-vessels at the tendon-bone interface atdifferent time intervals are summarized inTable 3. The numbers of neo-vessels andthe cells with positive immunostain aresignificantly higher in the shockwave groupthan the control group, and the differencewas statistically significant at different timeintervals (Fig. 7).

DiscussionSome authors speculated that

shockwaves relieved pain due to insertionaltendinopathy by hyper-stimulationanalgesia and increase of pain threshold.28

Other authors hypothesized the mechanismof microfracture including micro-disruptionof avascular or minimally vascular tissue toencourage revascularization and therecruitment of appropriate stem cellsconductive to bone healing.27,28 However,there are insufficient data to scientificallysubstantiate either theory concerning themechanism of shockwaves in musculoskeletaldisorders. Many recent studies in animalexperiments demonstrated the modulationof shockwave including neovascularization,osteogenic differentiation of mesenchymalstem cell and release of osteogenic and

Time Growth Shockwave Control P-value

indicator Mean ± SD Mean ± SD

1-week (N=3) eNOS 256±21 112±18

11

angiogenic growth factors.22,23,29,37

Therefore, extracorporeal shockwavesproduced effects of tissue regenerationand/or repair in musculoskeletaltissues, rather than a mechanicaldisintegration.

Many studies demonstrated thatover-expressions of eNOS and VEGFinduced angiogenesis.24,25 The resultsof the current studies demonstratedfor the first time that mechanicalshockwaves stimulated the ingrowth ofneovascularization associated withincreased expressions of angiogenicgrowth markers including eNOS, VEGFand PCNA in tendon, bone andtendon-bone interface.Neovascularization may play a role toimprove blood supply and healing oftendon and bone. Rompe et al38

reported a dose related effects ofshockwave on rabbit tendon Achilles.Wang et al39 demonstrated thatshockwave treatment showeddose-dependent enhancement of bonemass and bone strength after fractureof the femur. The results of thesestudies showed that the effect ofshockwave in musculoskeletal tissuesappeared to be time-dependent as wellas being dose-dependant. Therefore,it seemed likely that physicalshockwaves raised themechanotransduction and convertedinto biological signals that lead to acascade of biological responses intendon, bone and tendon-boneinterface (Fig. 8).

ConclusionThe biological mechanism of

musculoskeletal shockwaves appearedto initially stimulate the expressions ofangiogenic growth factors, andsubsequently the ingrowth ofneovascularization and improvementin blood supply that lead to repair oftendon and bone. Musculoskeletalshockwaves produced consistentbiological effects in tendon and boneand at the tendon-bone interface.In contrast to lithotripsy whereshockwaves are used to disintegrateurolithiasis, shockwaves in orthopedics(orthotripsy) are not been used todisintegrate tissues, but rather tomicroscopically cause interstitial andextracellular biological effectsincluding tissue regeneration.

AcknowledgementThese studies were partially or

totally supported by grants. Thesources of grants are from Chang GungResearch Fund (CMRP 83001) andNational Science Council (NSC91-2314-B-182A-068). No fund was received orwill be received from a commercialparty directly or indirectly related tothe subjects of this article.

The authors like to thank Ya-ZuYang, Yi-Chi Sun and Ya-Hsieh Chuangfor their technical assistances andcollection of data in the studies.

References1. Haupt G. Use of extracorporeal shock

wave therapy in the treatment ofpseudoarthrodesis, tendinopathy andorthopaedic disease. J Urology 1997;158:4-11.

2. Rompe JD, Rosendahl T, Schöllner C,et al. High-energy extracorporeal shockwave treatment of nonunions. ClinOrthop 2001; 387: 102-111.

3. Schaden W, Fischer A and Sailler A.Extracorporeal shock wave therapy ofnonunion or delayed osseous union.Clin Orthop 2001; 387: 90-94.

4. Wang CJ, Chen HS, Chen CE, et al.Treatment of nonunions of long bonefractures with shock waves. ClinOrthop 2001; 387: 95-101.

5. Loew M, Daecke W, Kuznierczak D, etal. Shock-wave therapy is effective forchronic calcifying tendonitis of theshoulder. J Bone Joint Surg 1999; 81B:863-867.

6. Rompe JD, Rumler F, Hopf C, et al.Extracorporeal shock wave therapy forcalcifying tendinitis of the shoulder.Clin Orthop 1995; 321:196-201.

7. Speed CA, Richards C, Nichols D,Burnet S, Wiles JT, Humphrey H,Hazlemann BL. Extracorporeal shockwave therapy for tendonitis of therotator cuff. A double-blind,randomized, controlled trial. J BoneJoint Surg. (Br) 2002; 84: 509-12

8. Wang CJ, Ko JY, Chen HS. Treatmentof calcifying tendonitis of the shoulderwith shock wave therapy. Clin Orthop2001;387: 83-89.

9. Wang CJ, Yang KD, Wang FS. Shockwave therapy for calcifying tendinitisof the shoulder. A two- to four-yearfollow-up. Am J Sports Med 2003;31(3):425-30.

10. Hammer DS, Rupp S, Ensslin S, et al.Extracorporeal shock wave therapy inpatients with tennis elbow and painfulheel. Arch Orthop Trauma Surg 2000;120:304-307.

11. Ko JY, Chen HS, Chen LM. Treatmentof lateral epicondylitis of the elbowwith shock waves. Clin Orthop 2001;387: 60-67.

12. Rompe JD, Hopf C, Kullmer K, et al.Analgesic effect of extracorporealshock wave therapy on chronic tenniselbow, J Bone Joint Surg 1996; 78B:233-237.

13. Speed CA, Nichols D, Richards C,Humphrey SH, Wiles JT, Burnet S,Hazlemann BL. Extracorporeal shockwave therapy for lateral epicondylitis- a double-blind, randomized,controlled trial. J Orthop Res. 2002;20: 895-8.

14. Chen HS, Chen LM, Huang TW.Treat-ment of painful heel syndrome

with shock waves. Clin Orthop 2001;387: 41-46.

15. Ogden JA, Alvarez R, Levitt R, et al.Shock wave therapy for chronicproximal plantar fasciitis. Clin Orthop2001; 387:47-59.

16. Rompe JD, Hopf C, Nafe B, et al.Low-energy extracorporeal shockwave therapy for painful heel: Aprospective controlled single-blindstudy. Arch Orthop Trauma Surg1996; 115:75-79.

17. Perlick L, Schifmann R, Kraft CN,Wallny T, Diedrich O. Extracorporealshock wave treatment of the Achillestendonitis: Experimental andpreliminary clinical results. Z OrthopIhre Grenzgeb 2002; 140(3): 275-80.

18. Delius M, Draenert K, Al Diek Y, et al.Biological effect of shockwave: In vivoeffect of high-energy pulses on rabbitbone. Ultrasound Med Biol 1995;21:1219-1225.

19. Johannes EJ, Kaulesar-Sukul DM,Metura E, et al. High-energy shockwaves for the treatment of nonunions:An experiment on dogs. J Surg Res1994; 57:246-254.

20. Kaulesar Sukul DM. Johannes EJ.Pierik EG. van Eijck GJ. Kristelijn MJ.The effect of high-energy shockwaves focused on cortical bone:An in vitro study. J Surg Res 1993; 54:46-51.

21. Wang CJ, Huang HY, Chen HH, et al.Effect of shock wave therapy onacute fractures of the tibia. A studyin a dog model. Clin Orthop 2001;387:112-118.

22. Wang CJ, Huang HY, Pai CH: Shockwave therapy enhanced neovascular-ization at the tendon-bond junction:an experiment in dogs. J Foot AnkleSurg 2002; 41: 16-22.

23. Wang CJ, Yang KD, Wang FS, HuangCC, Yang LJ. Shock wave inducesneovascularization at the tendon-bonejunction. A study in rabbits. J OrthopRes 2003; 21:984-989.

24. Babaei S, Stewart DJ. Overexpressionof endothelial NO synthase inducesangiogenesis in a co-culture model.Cardiovascular Res. 2002; 55: 190-200.

25. Spyridopoulos I, Luedeman C, ChenD, Kearney M, Murohara T, PrincipeN, Isner M, Losordo DW. Divergenceof angiogenesis and vascularpermeability signaling by VEGF:inhibition of protein kinase Csuppresses VEGF-inducedangiogenesis, but promotesVEGF-induced NO-dependent vascularpermeability. Arteriosclero, Thromboand Vas Biol 2002; 22: 901-6.

26. Nagashima M, Tanaka H, Takahashi A,Tanaka K, Ishiwata T, Asano G,Yoshino S. Study of the mechanism

involved in angiogenesis and synovialcell proliferation in human synovialtissues of patients with rheumatoidarthritis using SCID mice. Lab Invest2002; 82(8): 981-8.

27. Ogden JA, Toth -Kischkat A,Schultheiss R. Principles of shockwave therapy. Clin Orthop 2001; 387:8-17.

28. Thiel M: Application of shock wavesin medicine. Clin Orthop 2001; 387:18-21.

29. McCormack D, Lane H, McElwain J.The osteogenic potential of extracor-poreal shock wave therapy: An in-vivostudy. Ir J Med Sci 1996; 165:20-22.

30. Maier M, Milz S, Wirtz DC, Rompe JD,Schmitz C. Basic research of applyingextracorporeal shockwaves on themusculoskeletal system. An assess-ment of current status. Orthop 2002;31: 667-77.

31. McCormack D, Lane H, McElwain J.The osteogenic potential of extracor-poreal shock wave therapy: An in vivostudy. Irish J Med Sci 1996; 165: 20-22.

32. Wang FS, Wang CJ, Sheen-Chen SMet al. Superoxide mediates shockwave induction of RRK-dependentosteogenic transcription factor(CBFA 1) and mesenchymal cellsdifferentiation toward osteoprogenitors.J Biol Chem 2002; 277: 10931-7

33. Wang FS, Yang KD, Wang CJ, et al.Extracorporeal shock wave promotesbone marrow stromal cell growthand differentiation towardosteoprogenitors associated withTGF-b 1 induction. J Bone JointSurg 2002; 84B: 457-61.

34. Wang FS, Wang CJ, Huang HC, et al.Physical shock wave mediatesmembrane hyperpolarization andRas activation for osteogenesis inhuman bone marrow stromal cells.Biochemical Biophysical ResearchCommunications 2001; 287: 648-655.

35. Wang FS, Yang KD, Kuo YR, Wang CJ,Huang HJ, Chen YJ. Temporaland spatial expression of bonemorphogenetic proteins inextracorporeal shock wave-promotedhealing of fracture defect. Bone 2003;32:387-396.

36. Yang C, Heston WDW, Gulati S, FairWR. The effect of high-energy shockwaves (HESW) on human bonemarrow. Urol Res 1988; 16:427-42.

37. Wang CJ, Wang FS, Yang KD, WengLS, Sun YC, Yang YL. The effect ofshock wave treatment at thetendon-bone interface - Ahistomorphological and biomechanicalstudy in rabbits. J Orthop Res 2004(In press).

38. Rompe JD, Kirkpatrick CJ, Küllmer K,et al. Dose related effects of shock

waves on rabbit tendon Achilles. Asonographic and histological study. JBone Joint Surg 1998; 80B: 546-552.

39. Wang CJ, Yang KD, Wang FS, Hsu CC,Chen HS. Shock wave treatmentshows dose-dependent enhancementof bone mass and bone strength afterfracture of the femur. Bone 2004;34:225-230.

Fig. 8

NeovascularizationPCNAVEGFeNOSBMP

Improved blood supply

Tissue regeneration

Tendon repairBone repair

Biological responses

Physical S.W. energy

A proposed cascade of biological mechanism of extracorporeal shock waves in musculoskeletal tissues.

10

REPRINT REQUEST ANDCORRESPONDENCE TO:

Ching-Jen Wang, M.D.Department of OrthopedicSurgery Chang Gung MemorialHospital at Kaohsiung123 Ta-Pei Road, Niao-Sung HsiangKaohsiung, Taiwan 833Tel: 886-7-733-5279; Fax: 886-7-733-5515E-mail: w281211@adm.cgmh.org.tw

Running title: Biological mechanism ofmusculoskeletal shockwaves.

12 13

front limbs were treated with ESWT.The left front limb of each horse (G2)was not treated with ESWT (controlgroup). The progression of thehealing process in the ESWT-test andcontrol front limbs were monitoredultrasonographically throughout thestudy. These evaluations wereperformed before each of the3 treatments with ESWT (weeks 4, 7,and 10), and 2 and 4 weeks after thelast ESWT (weeks 12 and 14). At theend of the study (120th day after thecollagenase treatment), a tendon wasbiopsied (1.0 X 0.5-cm). After a12-hour fast, each horse waspremedicated with xylazine (1.1 mg/kg, IV) and anesthesia wasinduced with ketamine (2 mg/kg, IV)and diazepam (0.05 mg/kg, IV) andmaintained with continuous IVinfusion of guaifenesin (100 mg/kg),ketamine (2 mg/kg), and xylazine(1.1 mg/kg) to submitted to thesurgical procedure for a tendonbiopsy. Subsequently, horses wererecovered from anesthesia and werekept on stall.

Histological analysis. The fragmentcollected for histology were fixed in10% buffered formalin and routinelyprocessed. Sections were stained withhematoxylin-eosin and Massontrichrome. Histological analysis wasperformed under the light microscopeby an examiner who was unaware ofthe group to which the slidesbelonged. The following featureswere considered: number andcharacteristics of fibroblasts, presenceof an infiltrate and vascularization,presence of collagen fibers andparallelism of collagen fibers scoredon a scale from 0 to 3 (0=absence ofparallelism of collagen fibers, 1+discrete parallelism of collagen fibers,2= presence of 50% of collagen fibersand 3= total parallelism of collagenfibers.

Statistical analyses wereperformed by using a Friedman rankpoint analysis of variance, Wilcoxontest for dependent qualitativesamples, and Mann-Whitney tests forindependent samples. The level ofsignificance was set at p = 0,05.

ResultsSeven days after the collagenase

injections, ultrasonographicevaluations revealed 28,02 and32,70 percentage of the tendonlesions on control and test groups

respectively (table 1). Test andcontrol groups weren't significantlydifferent eather for ecogenicity orpercentage of lesion area, except forthe 90 th day. Therefore the fiberalignment scores for test group wereincreasing faster than for controlgroup which was statisticallysignificant at the end of theexperiment.

Few adverse effects such assmall areas of hair loss andsubsequent development of whitehair after treatment.

DiscussionThe collagenase model has

previously been used for theevaluation of the tendon healing inhorses. This model provides acontrolled mechanism for pairedcomparisons and it has beenconsidered an efficient model fortendinitis study.7,8

The repair process can bemonitored by noninvasive methods,such as ultrasonography or byinvasive methods, such as biopsy oftendons for histologic examination,allowing evaluation for the cellularityand the degree of disorganization ofthe extracellular matrix.9

In horses with collagenase-inducedsuperficial digital flexor tendinitisused in the present study,ultrasonographic evaluations revealed

that treatment of affected tendonswith ESWT had decreased the meanpercentage lesion on 90th and 120thdays more than in control group andbetter ecogenicity score on 60th and90th than control group. Our datacorroborate from findings of otherstudies6,10 as to the use of ESWTin horses with collagenase-inducedsuspensory ligament desmitis, exceptthat they had significant differences.

The mean fiber alignmentultrasonography score differedsignificantly between test and controlgroups. The longitudinal tendon fiberalignment occurred on ESWT group(G1) is an important parameter toreturn the horses with superficialdigital flexor tendinitis to theprevious level of activity withoutrelapse.7

Although the mean value of494,5 fibroblasts per mm2 in theESWT test group did not differsignificantly from 789,5 per mm2 incontrol group, the treatment's valuewas close to 459 fibroblasts per mm2

proposed as normal for horse tendonsby authors.1,7 These data allowed usto speculate that the lower number offibroblast detected in the test group(G1) may represent a later remodel-ing phase in the repair process.

The small amount of residualneoformed vessels and mononuclearinfiltrate observed in the group

AbstractIn the present study, the effects of

the extracorporeal shock wave therapy(ESWT) was assessed in experimentalequine tendinitis. Extracorporeal shockwave therapy may stimulate collagenfiber orientation permitting betterreorientation of the repair tissue. Tenhorses without health problems wereused in this experiment. Superficialdigital flexor tendinitis was induced inboth front limbs of each horse by useof a collagenase injections in eachsuperficial tendon. On the thirtiethday after the collagenase injection, theright front limb of each horse wastreated with ESWT (3 treatments at3-week intervals); the left front limbwas not treated (control limb).Periodically during the study, thehealing process was monitoredultrasonographically and theproportions of tendons affected withlesions were assessed. On the120th day of the experiment, biopsyspecimens were collected from alltendons for histological evaluation.The present results indicate thatESWT improved scar remodeling andtendon wound collagen maturation.

Key words: Shock wave, healing,tendinitis, equine.

IntroductionEquine tendons are frequently hurt

by different mechanisms and thelesions showed degenerativephenomena and inflammatoryalterations of different degrees ofintensity. The healing of these lesionsis often unsuccessful concerningrestoration of the morphologic andfunctional characteristics of the

tendon, thereby compromising thefuture athletic performance orincreasing the risk of recurrence oflesions in the affected horses.1

Many types of treatments have beenused to facilitate healing, but there arecurrently few treatments that stimulatehealing to proceed in a timely manneron a consistent basis.2, 3 As one wouldsuspect by the number of therapiesthat have been tried, none promotehealing in a timely fashion to allowearlier return to normal function.Although long convalescence seems tobe the most effective treatment, thereis still high relapse when the horsereturns to its normal workload.

New treatments such asextracorporeal shock wave therapy(ESWT) represent an option for thetreatment of superficial digital flexortendinitis in horses.3 The ESWT goalis not just to get horse back to worksooner but to promote a better healingi. e. normal collagen alignment of thetendon.3,4 The use of ESWT inVeterinary is at the beginning. So far,there is little information aboutdifferent indications, treatmentregimens and long-term results.Recent studies have shown that shockwave induce neovascularization at thetendon-bone junction, which in turnrelieves pain and improves tissueregeneration and repair.5 Results ofanother recent study suggested thatESWT in horses with suspensoryligament desmitis resulted in increasedamounts of collagen fibrils andextracellular matrix components andhigher immunoreactivity for TGF≤-1(which may possibly representincreased activity of fibroblasts) inaffected ligaments.6 Few controlled

studies have been carried out toinvestigate the experimental use of theextracorporeal shock waves in horses.The purpose of this study was toevaluate the effects of ESWT onaffected tendons of horses withexperimentally induced superficialdigital flexor tendinitis using ultrasonographic and histologicaltechniques.

Materials and Methods This study was approved by the

Ethics in Animal ExperimentationCommittee of Unesp-Botucatu. Tenadult horses (5 males and 5 females)were included in this study. Theanimals were clinically healthy adultArabian horses on average five yearsold, specifically selected in terms of anormal locomotor apparatus.

Superficial digital flexor tendinitiswas induced in both front limbs ofeach horse by use the type Icollagenase injections, 1ml, 2,5mg/ml,in the middle metacarpal third. Foreach collagenase treatment, the horseswere each sedated with romifidine(0.1 mg/kg, IV) and 2% lidocaineadministered in each front limb toprovide local anesthesia of the palmarmetacarpal and palmar nerves and theskin of the lateral metacarpal regionwas prepared aseptically. According toultrasound guidance, collagenase wasinjected into the lateral region of themetacarpus, reaching the center of thesuperficial digital flexor tendon, usingdisposable 30 X 8 hypodermal needle.

Immediately before and 1 weekafter each collagenase treatment,ultrasonographic evaluation of thecollagenase-induced lesions in eachfront limb was performed using a7.5-MHz linear transducer. The extentof each lesion was calculated from themeasurement of the area of the tendonand the area of the lesion.8 Thirtydays after the collagenase treatment,the horses were sedated withromifidine (0.1 mg/kg IV), and weretreated in the right front limb withfocused ESWT (G1). It involvedapplications of 500 shocks (5-mmfocus) over the lateral aspect,500 shocks (5-mm focus) over themedial aspect, and 500 shocks(35-mm focus) over the plantar aspectof the scanned region of superficialdigital flexor tendon and the energydensity was 0.15 mJ/mm2. Everythree weeks for three times, thehorses were sedated and their right

Effects of extracorporeal shock wave treatmenton equine tendon healing

Ana Liz G. Alves, DVM, PhD; Brunna PatríciaAlmeida da Fonseca DVM, Ms; Renée L.Amorim, DVM, PhD; Armen Thomassian, DVM,PhD; Carlos A. Hussni, DVM, PhD;José Luis M. Nicoletti, DVM, PhD

From the Faculdade de Medicina Veterinária e Zootecnia,São Paulo State University, Botucatu - SP (Caminoto, Alves, Colla,Amorim, Thomassian, Hussni, Nicoletti); Supported by Fundaçãode Apoio aos Hospitais Veterinários da Unesp (research supportfoundation of Unesp Veterinary Hospital).

7th 30th 60th 90th 120th

Ecogenicity

G1* 3Aa** 2,5Aa 2ABa 1,5Ba 1Ba

G2 3Aa 2Aa 3Aa 2Aa 1Ba

Percentage of the lesion area

G1 28.02Aa** 18.68Ba 12.45Ca 6.42Da 3.02Da

G2 32.70Aa 24.00Ba 11.37Ca 9.53Ca 6.85Da

Collagen fibers parallelism

G1 0Aa** 1Aa 0Aa 1,5Ba 3Cc

G2 0Aa 0Aa 0Aa 1Aa 1Aa

Table 1. Mean values of ecogenicity in the lesion area, percentage of the lesion areaand parallelism score, observed in the experimental groups through ultrasonogra-phy examination on days 7, 30, 60, 90 and 120 of the experiment.

*G1 = test group; G2 = control group.For each group, medians followed by capital letters did not differ significantly (p>0.05). For eachphase, medians followed by small letters did not differ significantly (p>0.05).The results obtained in the histopatological examination performed on the 120 th day after the lesion,showed fibroplasia, as also reported in literature.1 We observed differences between groups in termsof degree of collagen fiber maturation based on the identification of a low number of fibroblasts perunit area with elongated nuclei, few residual neoformed vessels, a few traces of mononuclear inflam-matory infiltrate and a parallel arrangement of collagen fibers in test group, observed under themicroscope (Table 2).

14 15

submitted to ESWT (G1) indicated ahigher speed of maturation of therepair process compared with control(G2). Similar data were reported byWillians 9 who stated that thereduction of cellularity andvascularization suggests progressivematuration of granulation tissue.

The present results demonstratethat the parallel arrangement ofcollagen fibers in the ESWT test group(G1) was more evident than in controlgroup (G2) (table 2). Whencomparing these results with thosereported by Alves et al.7 and Goodshipand Birch,1,11 it can be observed thatduring the process of tendon repair,collagen fibrils are irregularlydeposited, with predominantlongitudinal alignment as the processmatures. In our study the process ofcollagen fiber remodeling was moreefficient in test group than in thecontrol one.

The fact that ESWT had stimulatedthe alignment of collagen fibers duringthe course of the repair process,led us to believe that the ESWT in thepresent experiment had a highbeneficial effect on the quality oftendon repair.1,11,12 Alves et al.7

emphasized the importance of the highdegree of parallelism of collagen fibers,demonstrating the correlation betweenthis characteristic and the increasedresistance of tendon fibers.

We concluded that the effect ofESWT on tendon lesions allowedfor a significant improvement in thequality of the tendon repair andfavorable prognosis for the horseprincipally due to the arrangement ofthe collagen fibers.

The next phase of a future studycould be the investigation of theproportion of the two types ofcollagen fibers (I and II) in thisrepair tissue and the mechanicalproperties of the scar.

References1. Goodship AE, Birch HL, Wilson AM.

The pathobiology and repair of tendonand ligament injury. Vet Clin North AmEquine Pract. 1994;10(2):323-349.

2. Dyson S. Proximal suspensorytendinitis in the forelimb and thehindlimb. In: Proceedings. Am AssocEquine Pract. 2000;46:127-142.

3. McClure SR, Evans RB. In vivoevaluation of extracorporeal shockwave therapy for collagenase inducedsuspensory ligament tendinitis. In:Proceedings. Am Assoc Equine Pract.2002;48:378-380.

4. Boening KJ, Löffeld S, Weitkamp K,Matuschek S. Radial extracorporealshock wave therapy for chronicinsertion desmopathy of the proximalsuspensory ligament. In: Proceedings.Am Assoc Equine Pract. 2000;46:203-207.

5. Wang CJ, Paich, Avery SY. Shock wavesenhanced neovascularization. at thetendon bone junction. An experimentaldog model, In proceedings. 3rdCongress Of The International SocietyFor Musculoskeletal Shock WaveTherapy, 2000; 96.

6. Caminoto EH, Alves ALG, Amorim RL,Thomassian A, Hussni CA, Nicoletti JL.Ultrastructural and immunocytochemi-cal evaluation of the effects ofextracorporeal shock wave treatmentin the hind limbs of horses withexperimentally induced suspensoryligament desmitis. Am J Vet Res. 2005;66 (5):892-896.

7. Alves ALG, Rodrigues MAM, Aguiar

AJA, Thomassian A, Nicoletti JLM,Hussni CA, Borges AS. Effects ofbeta- aminopropionitrile fumarate andexercise on equine tendon healing:Gross and histological aspects. JEquine Vet Sci. 2001; 21(7):335-340.

8. Foland JW, Trotter GW, Powers BE,Wrigley RH, Smith FW. Effect ofsodium hyaluronate in collagenase-induced superficial digital flexortendinitis in horses. Am J Vet Res.1992; 53(12):2371-2376.

9. Williams IF, McCullagh KG, GoodshipGD, Silver IA. Studies on thepathogenesis of equine tendonitisfollowing collagenase injury. Res VetSci. 1984; 36:326-338.

10. McClure SR, VanSickle D, Evans R,Reinertson EL, Moran L. The effects ofextracorporeal shock-wave therapy onthe ultrasonographic appearance ofcollagenase-induced equine forelimbsuspensory ligament desmitis.Ultrasound in Med & Biol. 2004; 30(4):461-467.

11. Crowe O, Dyson SJ, Wright IM,Schramme MC, Smith RKW. Treatmentof 45 cases of chronic hindlimbproximal suspensory desmitis by radialextracorporeal shockwave therapy. In:Proceedings. Am Assoc Equine Pract.2002;48:322-325.

12. Kersh KD, McClure S, Evans RB,Moran L. Ultrasonographic evaluationof estracorporeal shock wave therapyon collagenase-induced superficialdigital flexor tendonitis. In:Proceedings. Am Assoc Equine Pract.2004;50:257-260.

a Collagenase type I, Sigma, USAb Sedivet, Boehringer Ingelheim, Brasilc Lidocaína 2%, Cristália, Brasild SSD 900, Aloka, Japane Versatron, HMT, Swissf Sedazine, Fort Dodge, Brasilg Vetanarcol, Konig, Brasilh Valium, Roche, Brasili EGG, Henrifarma, Brasil

Table 2. Mean values of number of fibroblast cells in the lesion area and ofparallelism score, observed in the experimental groups through histopathologicalexamination on the 120th day of the experiment.

G1 G2

Mean fibroblast number 494.5a* 789.5a

Median parallelism score 3a 1b

*G1 = test group; G2 = control group.For each group, medians followed by lower case letters were did not differ significantly (p>0.05).

Newsletter of ExtracorporealShockwave Therapy is an international,peer-reviewed journal produced byInternational Society for MusculoskeletalShockwave Therapy(ISMST) and is issuedthree times a year.

Newsletter of ExtracorporealShockwave Therapy offers the opportunityto publish original research, clinical studies,review articles, case reports, clinicallessons, abstracts, book reviews,conference reports and communicationsregarding the scientific or medical aspectsshockwave therapy.

Manuscript SubmissionAll manuscripts should be sent to the

Editor: By e-mail: prds@uol.com.brOn disk and mail to:Dr Paulo Roberto Dias dos SantosRua Nathanael Tito Salmon, 233Osasco - São Paulo - BrazilCEP 06016-075 We encourage authors to submit

manuscripts via e-mail. When submitting bye-mail, print mail address and telephoneand fax numbers also should be included.

Manuscript Categories All articles should be well-written in

plain English, whereby jargon, acronyms,abbreviations and complicated data shouldbe avoided. Scientific research:

Theoretical or experimental (basic orapplied) scientific research or the practicalapplication of this research. The articleshould consist of an abstract, key words,introduction, methods, results, discussion,and conclusion.

Length: The manuscript should be nolonger than 2,500 words, including title page,abstract, references, legends and tables.Review articles:

Review articles on topics of generalinterest are welcomed. Reviews shouldinclude the specific question or issue thatis addressed and its importance for theshockwave therapy community, andprovide an evidence-based, balancedreview on this topic. The article shouldinclude a description of how the relevantevidence was identified, assessed forquality, and selected for inclusion;synthesis of the available evidence suchthat the best-quality evidence shouldreceive the greatest emphasis; anddiscussion of controversial aspects andunresolved issues. Meta-analyses also willbe considered as reviews. Authorsinterested in submitting a review manuscriptshould contact the editorial office prior tomanuscript preparation and submission.

Length: Approximately 2,000 to 2,500words and no more than 40 references. Case reports

Authors are encouraged to submitarticles with interesting case reports withrelevant information regarding diagnosisand therapy, unique for shockwavetherapy. The articles should be short,accurate and easy to understand, andshould consist of the following:

- A summary with the clinical relevance;

- An introduction explaining the clinicalproblem;

- A short report of the cases, consistingof history, physical examination, furtherinvestigation, treatment and follow-up.

- A discussion, whereby the clinicalconsequences are described and the mostinteresting aspects of the case report.

Length: Approximately 750 to 1,200words and a maximum of 15 references. Clinical lesson

Authors are invited to give a descriptionand background information ofdevelopments in the field of furtherdiagnostics and clinical tests and methodsthat are relevant to all aspects ofshockwave therapy, training andrehabilitation. It is not necessary toinclude examples of patients, as in casereports. The articles should be up-to-date,short, accurate, and easy to understandand should contain the following:

- A summary with the clinicalrelevance (max. 150 words)

- And introduction with the theme ofthe article

- A description of the used test methodor diagnostic

- A conclusion with the practicalrelevance and practical tips.

Length: Approximately 750 to 1,200words and a maximum of 5 references.National organisationcommunications

National organisations are invited todescribe any aspect of medical care orscience in their country, e.g. the functionof their medical committee, medical careof their players, research that is beingconducted etc.

Approximately 300 to 500 wordsLetters to the editor:

Letters discussing an article that hasbeen published in Journal ofExtracorporeal Shockwave Therapy havethe greatest chance of acceptance if theyare sent in with 2 months of publication.Letters that are approved will be forwardedto the author, who will have 6 weeks torespond. The original letter and the replywill be published simultaneously.

Length: Such letters should not exceed400 words of text and 5 references.Research Letters reporting originalresearch also are welcome and should notexceed 600 words of text and 6 referencesand may include a table or figure.Review of the Literature

Authors are invited to submitsummaries of published article of particularinterest for the shockwave therapycommunity. The opinion of the authorshould be stated following each summary.

Length: Such a review should beapproximately 500 to 700 words. A reviewof three articles simultaneously should beno longer than 1,000 words. Conference reports and Abstracts

Authors are invited to submit reportsof conferences they have attended, and toinclude one to three photographs taken atthe meetings. Please include the namesand highest titles of the persons that canbe identified in the photographs.Summaries of work presented at theconference may be submitted forpublication as well.

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– Journal: Kibler WB. The role of thescapula in athletic shoulder function. Am JSports Med. 1998;26(2):325-337.

– Book: Perry J. Biomechanics of theshoulder. In: Rowe CR, ed. The shoulder.London: Churchill Livingstone, 1988:1-15.

• Footnotes should be avoided.

Review processContributions will be reviewed by the

editorial board for scientific research,review papers, case reports, clinicallessons, and abstracts. Manuscripts shouldmeet the following criteria: material isoriginal; writing is clear; study methods areappropriate; the data are valid; conclusionsare reasonable and supported by the data;information is important; and topic hasgeneral shockwave therapy interest.

Manuscripts with insufficient priorityor quality for publication are rejectedpromptly. Other manuscripts are sent toexpert consultants for peer review. Peerreviewer identities are kept confidential,but author identities are known byreviewers. The existence of a manuscriptunder review is not revealed to anyoneother than peer reviewers and editorial staff.

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PODER rápido e prolongado

Referência bibliográfica: 1. Malmstrom K, Sapre A, Coughlin H et al. Etoricoxib in acute pain associated with dental surgery: A randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Clin Ther 2004;26(5):667-679.

Resumo do estudo: estudo com distribuição randômica, de grupos paralelos, que envolveu 398 pacientes com dor moderada a intensa após extração de, pelo menos, dois terceiros molares. Os pacientes receberam uma dose única de 60 mg, 120 mg,180 mg ou 240 mg de ARCOXIA, 400 mg de ibuprofeno e placebo. Os pacientes interromperam dois cronômetros durante o tratamento: quando alcançavam alívio perceptível da dor e quando alcançavam alívio significativo da dor. A intensidade e o alívioda dor foram medidos já 15 minutos após a administração da dose. O início da analgesia ocorreu já 24 minutos após a dose em pelo menos 50% dos pacientes tratados com 120 mg de ARCOXIA e a analgesia persistiu por até 24 horas após a dose em72% dos pacientes tratados com essa dose; as doses mais altas de ARCOXIA não proporcionaram nenhum efeito clínico adicional.

ARCOXIA (etoricoxibe), MSD. INDICAÇÕES: tratamento agudo e crônico dos sinais e sintomas da osteoartrite e da artrite reumatóide, da gota aguda e da dismenorréia primária; alívio da dor aguda e crônica. CONTRA-INDICAÇÃO: hipersensibilidade a qualquer componente doproduto. PRECAUÇÕES: ARCOXIA não é recomendado para pacientes com doença renal avançada; se o tratamento for necessário, recomenda-se monitorização rigorosa da função renal desses pacientes. Deve-se ter cautela ao iniciar o tratamento com ARCOXIA em pacientes comdesidratação considerável e considerar a possibilidade de retenção hídrica, edema ou hipertensão quando ARCOXIA for utilizado em pacientes com edema, hipertensão ou insuficiência cardíaca preexistentes. Os médicos devem estar cientes de que determinados pacientes podem desen-volver úlcera(s) no trato gastrintestinal superior, independentemente do tratamento, especialmente naqueles com mais de 65 anos de idade. Foram relatados aumentos de ALT e/ou AST em cerca de 1% dos pacientes tratados durante mais de um ano em estudos clínicos; essas alteraçõesdesapareceram em seguida e, em cerca de metade dos casos, sem interrupção do tratamento. Em caso de disfunção hepática persistente, ARCOXIA deve ser descontinuado. ARCOXIA deve ser utilizado com cautela por pacientes que já tenham apresentado crises agudas de asma,urticária ou rinite causadas pelo uso de salicilatos ou inibidores não específicos da cicloxigenase. ARCOXIA pode mascarar a febre, que constitui um sinal de infecção. ARCOXIA só deve ser usado durante os dois primeiros trimestres da gravidez se o benefício potencial justificar o possívelrisco para o feto. Não se sabe se ARCOXIA é excretado no leite humano; por isso, quando ARCOXIA for administrado a nutrizes deve-se considerar a importância do medicamento para a mãe ao se decidir entre descontinuar a amamentação ou a medicação. A segurança e a eficáciaem pacientes pediátricos não foram estabelecidas e, em geral, não foram observadas diferenças no perfil de segurança e na eficácia do medicamento entre pacientes idosos (65 anos de idade ou mais) e pacientes mais jovens. INTERAÇÕES MEDICAMENTOSAS: Tratamento crônicocom varfarina: a administração de 120 mg de ARCOXIA uma vez ao dia foi associada com aumento no tempo de protrombina de aproximadamente 13% (International Normalized Ratio - INR). Rifampicina: ocorreu redução de cerca de 65% das concentrações plasmáticas doetoricoxibe quando este foi administrado com a rifampicina. Metotrexato: doses de 60 mg e 90 mg ao dia de ARCOXIA durante 7 dias não exerceram efeito na concentração plasmática ou na depuração renal de 7,5 mg a 20 mg de metotrexato em doses únicas semanais para otratamento da artrite reumatóide. Em um estudo, a dose de 120 mg de ARCOXIA aumentou a concentração plasmática do metotrexato em 28% e reduziu a depuração renal do metotrexato em 13%; por isso, deve-se monitorar a toxicidade relacionada ao metotrexato quando foremadministradas doses maiores que 90 mg de ARCOXIA ao dia com essa medicação. Inibidores da ECA: relatos sugerem que pode haver diminuição dos efeitos anti-hipertensivos dos inibidores da ECA quando ARCOXIA for administrado com essas medicações. Lítio: relatos sugerem quepode haver aumento dos níveis plasmáticos de lítio quando ARCOXIA for administrado com lítio. Ácido acetilsalicílico em baixas doses: pode ser utilizado concomitantemente a ARCOXIA; este, porém não exerce efeitos sobre as plaquetas e não substitui o ácido acetilsalicílico paraprofilaxia cardiovascular. REAÇÕES ADVERSAS: as seguintes experiências adversas relacionadas à medicação foram relatadas (incidência ≥1%) em estudos clínicos de 12 semanas sobre osteoartrite, artrite reumatóide ou dor lombar crônica: astenia/fadiga, tontura, edema demembros inferiores, hipertensão, dispepsia, pirose, náuseas, cefaléia e aumento de ALT e AST. O perfil de experiências adversas relatadas nos estudos sobre gota aguda e analgesia aguda foi similar ao relatado nos estudos combinados de osteoartrite, artrite reumatóide e dor lombarcrônica. POSOLOGIA: Osteoartrite: 60 mg uma vez ao dia. Artrite Reumatóide: 90 mg uma vez ao dia. Gota Aguda: 120 mg uma vez ao dia (somente durante o período sintomático agudo). Dor Aguda e Dismenorréia Primária: 120 mg uma vez ao dia (somente durante o períodosintomático agudo). Dor Crônica: 60 mg uma vez ao dia. (Doses maiores que as recomendadas para cada indicação ou não apresentaram eficácia adicional ou não foram estudadas; portanto, as doses acima são as doses máximas recomendadas.) Insuficiência Hepática: em pacientescom insuficiência hepática leve (escore de Child-Pugh 5-6), a dose de 60 mg uma vez ao dia não deve ser excedida. Em pacientes com insuficiência hepática moderada (escore de Child-Pugh 7-9), a dose de 60 mg em dias alternados não deve ser excedida. Não há dados clínicosou farmacocinéticos em pacientes com insuficiência hepática grave (escore de Child-Pugh >9). Insuficiência Renal: o tratamento com ARCOXIA não é recomendado para pacientes com doença renal avançada (clearance de creatinina