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Home>CanineOsteoarthritis:Understandingtheetiology,clinicalpresentation,anddiagnosis

CanineOsteoarthritis:Understandingtheetiology,
clinicalpresentation,anddiagnosis
Oct01,2004
ByStevenC.Budsberg,DVM,MS,DACVS
Osteoarthritisisthemostcommonrheumaticdiseaseencounteredinsmallanimal
practice.Nolongerisosteoarthritisregardedasasimpleconsequenceofagingand
cartilagedegeneration,butrather,thepathologicchangesofosteoarthritismayresult
fromactivebiochemicalandbiomechanicalprocessespartlyduetodisturbancesof
thehomeostaticmechanismsofanabolicandcatabolicpathways.Astothecauseof
osteoarthritis,thereisnooneetiologyanditscausemaybemultifactorial.While
therearemanyinitiatingcauses,osteoarthritisisanirreversibleprocessthatoften
resultsinanendstageclinicalsyndromeofthejoint.Osteoarthritisexhibitsvarying
degreesofseverity,rangingfromamild,intermittentconditionthatcausesmild
discomfortandminimaldisability,toaclinicalstatecharacterizedbyconstantpain
andseveredisability.Clinically,osteoarthritiscanbeachallengingdiagnosisto
make.Thediseaseistypicallyaslowlyprogressiveproblem.Becauseofthewide
rangeofpresentingsigns,osteoarthritisislikelyoneofthemostunderdiagnosed
syndromesindogsand,especially,incats.1,2 Itafflictsatleast20%ofthecanine
populationatanytime.1,3 Thistranslatestoroughly10to12milliondogsinthe
UnitedStates.Therearenoaccurateestimatesofthenumberofcatswith
osteoarthritis.
Asingledefinitionofosteoarthritisremainselusive.Ata1995workshop,the
AmericanAcademyofOrthopaedicSurgeonsproposedthefollowingconsensus
definition:Osteoarthriticdiseasesarearesultofbothmechanicalandbiologicevents
thatdestabilizethenormalcouplingofdegradationandsynthesisofarticular
cartilagechondrocytes,extracellularmatrix,andsubchondralbone.Althoughthey
maybeinitiatedbymultiplefactors,includinggenetic,developmental,metabolic,and
traumaticfactors,osteoarthriticdiseasesinvolveallofthetissuesofthediarthrodial
joint.Ultimately,osteoarthriticdiseasesaremanifestedthroughmorphologic,
biochemical,molecular,andbiomechanicalchangesinbothcellsandmatrixthat
leadtosoftening,fibrillation,ulceration,articularcartilageloss,sclerosisand
subchondralboneeburnation,andosteophyteproduction.Whenclinicallyevident,
osteoarthriticdiseasesarecharacterizedbyjointpain,tenderness,movement
limitation,crepitus,occasionaleffusion,andvariabledegreesofinflammationwithout
systemiceffects.4
Pathophysiologyofosteoarthritis
Forsimplicity,thinkofosteoarthritisprogressioninthreebroadstages.5 Stageoneis
theproteolyticbreakdownofcartilagematrix.Stagetwoinvolvesfibrillationand
erosionofthecartilagesurface,accompaniedbybreakdownproductreleaseintothe
synovialfluid.Finally,duringstagethree,synovialinflammationbeginswhen
synovialcellsingestabreakdownproductthroughphagocytosisandproduce
proteasesandproinflammatorycytokines.However,thesestagesdon'tprogressina
specificorder.Morphologically,osteoarthritisischaracterizedbyarticularcartilage
degenerationandchangesintheperiarticularsofttissues(synoviumandjoint
capsule)andsubchondralbone.Specifically,thepathologicchangesofosteoarthritis
involvearticularcartilagedegeneration,whichincludesmatrixfibrillation,fissure
appearance,grossulceration,andfullthicknesslossofthecartilagematrix.This

pathologyisaccompaniedbyhypertrophicbonechangeswithosteophyteformation
andsubchondralboneplatethickening.Researchalsohasshownsomecontinuity
betweenboneandcartilagechangesinosteoarthritis,suggestinganinteraction
betweenthesetissues.6
Normalarticularcartilageisprimarilycomposedofwater(70%byweightinmature,
healthycartilage),acollagenfibrilnetwork,extracellularmatrix,andchondrocytes.
Duringnormalweightbearing,severaleventsoccurinthejoint.Thedifferentmatrix
componentsmustshareloadsappliedtothearticularsurface.Collagenfibrils
dominatethetensilebehaviorofcartilage,whiletheosmoticpropertiesofthe
proteoglycansprovideresistancetovolumetriccompression.Twoverydesirable
eventsoccurduringcartilageloading:cartilagedeformationandincreasedjoint
conformity.Cartilagedeformationincreasesoverallcontactarea,whichreduces
tissuestresslevels.Andincreasedjointconformityprovidesadditionaljointstability.
Furthermore,theabilitytochangetheshapeoftheloadedcartilagemayhelpform
andretainathingelofconcentratedlubricantbetweenthearticularsurfacesfluidis
distributedawayfromthecompressedregionsofcartilage.Thesepropertiesare
controlledprimarilybythecartilage'sabilitytomaintainhydrationunderpressure,
whichisachievedthroughthelowhydraulicpermeabilityandthehighosmotic
pressureoftheconstituentproteoglycans.
Anearlyeventinosteoarthritisdevelopmentistheincreasingvolume(swelling)of
thecollagen.Thiscanonlyoccurifthecollagennetwork'stensilepropertiesare
altered.Thelevelofaggrecan(aproteoglycan)alsochangesinthetissueearlyin
osteoarthritisdevelopment.
Cytokinesandgrowthfactorsappeartoplayacriticalroleintheinductionand
progressionofosteoarthritis.Proinflammatorycytokines,includinginterleukin1and
andtumornecrosisfactor,inducearticularcartilagedepletionbyincreasingthe
synthesisofmatrixdegradingenzymesanddecreasingmatrixproteinsynthesisin
vitro.
Themaintenanceofnormalcartilagehomeostasisrequiresthecoordinated
synthesisanddegradationofarticularcartilagematrixmacromolecules.Ifthis
balanceinturnoverisinterrupted,matrixdegradationisgreaterthanchondrocyte
replacementoflostmatrix.Ongoing,repetitiveinjuryseemstobeimportantto
cytokinesynthesis,andashiftinthebalancebetweenproinflammatoryandanti
inflammatorycytokinesmaycontributetothedestructiveprocess.Increasedmatrix
synthesisinosteoarthritis,whichoccursinresponsetoinjury,doesn'tappearto
counterbalancematrixloss.Thisisparticularlynoticeableinthecontentof
proteoglycan,whichdecreasesinosteoarthriticcartilage.Asmatrix
metalloproteinasesdamageanddepletethecollagenfibrilnetwork,theremaining
proteoglycansaccumulateadditionalwaterinanunconstrainedfashion,leadingto
increasedcartilagewatercontentandcartilageswelling.Histopathologicchanges
characteristicofosteoarthriticarticularcartilageincludeirreversiblechondrocyteloss
fromnecrosisorapoptosisandchondrocytecloning(ahallmarkofosteoarthritic
cartilage),fragmentationofthecartilagesurface,verticalclefts,bonyremodelingat
thejointperiphery,andpenetrationofthetidemarkbybloodvessels.Multiple
tidemarksareprogressivechangessuggestingincreasingseverity.Osteophytesor
enthesiophytesseenonradiographs,atnecropsy,andonhistologicsectionsare
oftenassociatedwithosteoarthritis,butalonearen'tsufficientforsuchadiagnosis.
Fromabiomechanicalpointofview,thecausesofcartilagedegenerationcanbe
simplifiedtonormalloadingonanabnormalsurfaceorabnormalloadingona
normalsurface.Laxityorincongruityinthejointplacesthetotalloadoverasmaller
areaofarticularcartilage,therebyincreasingthefocalstress.Thefinalresultis
cartilagethinningcausedbymatrixloss,physicalcompression,fragmentation,and
ulceration.59
Clinicalpresentationandriskfactors
Adiagnosisofosteoarthritisismadethroughclinicalsigns,physicalexamination
findings,radiographicfindings,and,occasionally,synovialfluidanalysis.Themost
commonclinicalsignisjointpainandassociatedlamenessthatmaybeacuteor
chronicindogs.10 Chronicpainresultingfromosteoarthritismaybedifficultto
recognize,asit'sfrequentlyinsidiousinonset.Thislikelyscenarioofundetected

chronicpainisespeciallytrueincats.Catsoftenpresentwithahistoryofreduced
appetite,weightloss,reluctancetomove,orfailuretoselfgroom.Osteoarthritis
shouldbeonthelistofdifferentialdiagnosesforcatswiththesenonspecific
complaints.2,10,11 Occasionallyinbothdogsandcats,morespecificsigns,including
therefusaltojumporanovertlimp,signalthepresenceofpain.Regardlessof
historicalfindings,physicalexaminationfindingsmayincludepain,crepitus,
swelling,jointeffusion,periarticularfibrosis,muscleatrophy,andadecreasedrange
ofmotionintheaffectedjoints.10,11 Allformsofjointdisease,includingimmune
mediateddisease,mayhavesimilarphysicalfindingstherefore,thecauseofjoint
diseasemustbeidentifiedbecausethetreatmentvariesaccordingly.Radiographic
osteoarthriticchangesusuallyoccurrelativelylateinthediseaseprocess.These
signsmayincludesclerosisofsubchondralbone,osteophyteformation,periarticular
fibrosis,andjointeffusion.12
Theinitialcausecanbetraumatic,mechanical,inflammatory,hereditary,or
idiopathic.Identificationandeliminationormodificationofriskfactorsisoneofthe
areaswherewemakethemostheadwayincontrollingosteoarthritis.Regardlessof
thecauseofinjury,cartilagehasaverylimitedabilityforintrinsicrepair,andcurrent
treatmentsforosteoarthritis,althoughcontinuouslyimproving,havesubstantial
limitations.Mostpathwaystothedevelopmentofosteoarthritisinvolve
developmentaldiseaseswithcomplexpolygeniccharacteristics,ratherthan
traumaticinjury.Andseveralotherfactors,suchaslifestyle,husbandry,environment,
andtheseverityofthegeneticdisease,playanimportantroleintheclinical
expressionoroutcomeofeachpatient'scondition.
Evenwhendogsaregenotypicallypredisposedtoosteoarthritis,evidencesuggests
thatalteringtheirenvironmentcanstronglyaffectthephenotypicexpressionofthe
gene.Weightisoneofthemostimportantfactorsinphenotypicexpressionof
osteoarthritis.Seminalresearchreportsdescribetheeffectsoflimitedfood
consumptionontheincidenceandseverityofhipdysplasiainLabradorretrievers
overtheirlifetime.1317 Themostdramaticfindingwasthatdogsfedadlibitumhad
significantlyworsehipdysplasiathandogsoffered25%lessfood.Similarly,research
incockerspanielsshowedthatdogswithcruciatediseaseandhumeralcondylar
fracturesweresignificantlyheavierthancontrols.18 Inpractice,weneedtoexplainto
petownersthatanincreaseinbodyweightandbodyconditionscoreincreasesthe
likelihoodofdogsexperiencinganinjuryordiseasethatpredisposesthemto
osteoarthritis.18
Clinicalmanagement
Currentosteoarthritistherapyismainlypalliative,aimingtoreducepainandmaintain
orimprovejointfunction.Osteoarthritismanagementshouldbethoughtofasamulti
stepapproachwiththreeequallyimportantcomponents:weightreduction,exercise
andphysicaltherapy,andpharmacologicmanagement.Thus,initiatingtreatment
requiresalengthydiscussionwiththeclientaboutallmanagementaspects.The
veterinarianmustexamineeachcasecarefully,assessingtheage,normalactivity
levels,and,mostimportant,theowner'sexpectationsfortheanimal'sperformance.
Successlargelydependsontheaccurateassessmentoftheseexpectations.10
Weightreduction
Weightcontrolisamustwhendealingwithosteoarthritis.Thevastmajorityofour
patientswithclinicalmanifestationsofosteoarthritisareobese.Ownereducationand
properdietarymanagementmustbeconsideredineverycase.Inmanycases,
weightreductionwithrestandexercisemodificationdiminishesorcompletely
alleviatestheclinicalsignsofosteoarthritis.
Exercisemodification
Usingthejointinamannerthatconsistentlycausesdiscomfortacceleratescartilage
destruction.Mostpatientswithosteoarthritisarecomfortablewithlighttomoderate
exerciseregimensthatdon'tvarygreatly.Enforcedrestandexercisemodification
shouldbeindividualizedforeachanimal,butexercisepeaksandvalleystendto
exacerbateclinicalsigns.Agoodreferencedocumentsphysicaltherapymethodsto

helptheosteoarthritispatient.19
Medications
Nonsteroidalantiinflammatorydrugs(NSAIDs)areusedintreatingosteoarthritis
becauseoftheirabilitytoreducepaintheyarethemainstayofchronicanalgesia
therapyinsmallanimalmedicine.Themajorweaknessofthesedrugsistoxicity.
Unwantedsideeffectsareespeciallyproblematicincats.AwidevarietyofNSAIDs
arenowavailabletheydecreaseprostaglandinsynthesisbyinhibitingthe
cyclooxygenase(COX)enzyme.20 AtleastthreedifferentCOXenzymesexist(COX
1,COX2,andCOX3)thatareactiveinarachidonicacidmetabolism,andcertain
NSAIDsareselectiveintheiractionsagainsttheseisoenzymes.10 NSAIDsthat
selectivelyinhibitCOX2andspareCOX1willallowanalgesiawithoutthecommon
sideeffectsofCOX1inhibition,whichincludealteredgastrointestinaland
thrombocytefunction.Thesenewerproductsarepotentiallysaferandaseffectivein
alleviatingpainasolderNSAIDs.Inaddition,extensivedatashowthatmanyofthe
antiinflammatoryeffectsofNSAIDsareincrementaltotheinhibitionofarachidonic
acidmetabolism.Additionally,thereisstrongevidencethatNSAIDsactdirectlyinthe
spinalcordandhighercenters.ThemechanismsofhowthedifferentCOX
isoenzymesareinvolvedingeneratingpainfulsensationsaren'tcompletely
understood.10
Bycriticallyevaluatingthecurrentstateofourtreatmentoutcomes,weseeaneedto
improveoureffectivenessintreatingosteoarthritispain.Clinicalexperienceand
experimentalstudiessuggestthatNSAIDsmaynotprovidecompletepainreliefin
canineosteoarthritis.2124Thus,amultimodalapproachfortreatingchronicpainmay
bethebestapproachforthefuture.Studiesrevealtheimportanceofaconstantinput
ofnoxioussignalsfromtheperipheryininducingchangesinthecentralnervous
systemsuchstudiesarebeginningtoredirectourtreatmentmethods.25Thenervous
systemisplasticandinputsfromtheperipherycanactivatevariousreceptorsand
changethewaynociceptivesignalsareprocessedinthespinalcord.26,27 This
cellular"windup"producescentralsensitizationthroughtheactivationofsecond
messengersystems,theproductionofnitricoxideandeicosanoids,andtheinduction
ofimmediateearlygenes.Currentresearchisactivelylookingintotheseareasand
mayprovidenewtreatmentoptionsinthenearfuture.
OtherthanNSAIDs,therearefewanalgesicsavailablethatcanbegivenchronically
intheclinicalsetting.Compoundsthatwillbediscussedactmoreindirectlythan
NSAIDs,eitherearlyintheinflammatorycascadeordirectlyonthetissues
themselves,thusindirectlyprovidinganalgesiceffects.10 Currentresearchisdirected
towardcompoundsthatareknownasdiseasemodifying,orstructuremodifying,
previouslycalledchondroprotectiveagents.Thesedrugscanaffectboththe
inflammatorycascadeandreleaseofmediatorsandalsothetargettissues(cartilage,
bone,andsynovium).Theonlydiseasemodifyingdruglicensedforveterinaryusein
theUnitedStatesispolysulfatedglycosaminoglycansolution(AdequanLuitpold).
Otherproductssuchaspentosanpolysulfateanddiacerhein,whichareapprovedin
othercountries,arecurrentlyundergoingadditionaltestingtoproveefficacyand
safetyintheUnitedStates.Therearemanyotherdrugclasses,suchas
bisphosphonatesandanticytokinecompoundsthatmayprovideadditionaloptionsto
helptreatchronicosteoarthritispaininthefuture.
Nutritionalsupplementsofglucosamineandchondroitinsulfateareavailable.
However,thereisminimalscientificdataavailablefortheseproductstoproveclinical
efficacyinosteoarthritispainreliefinthedogorcat.Anothernutritionalapproachthat
showssomepromiseistheuseoflongchainomega3fattyacids.Themostlikely
modeofactioninthemanagementofosteoarthritisappearstobetheinhibitionof
cytokines,eicosanoids,andothermediatorsinthecomplexinflammatorycascade.
References
1.Johnston,S.A.:Osteoarthritis:jointanatomy,physiology,andpathobiology.Vet.
Clin.NorthAm.27(4):6997231997.
2.Hardie,E.M.:Managementofosteoarthritisincats.Vet.Clin.NorthAm.27(4):945

9531997.
3.Moore,G.E.etal.:Causesofdeathorreasonsforeuthanasiainmilitaryworking
dogs:927cases(19931996).JAVMA219(2):2092142001.
4.Kuettner,K.Goldberg,V.M.:Osteoarthritisdisorders.Rosemont:American
AcademyofOrthopaedicSurgeons,Rosemont,Ill.,1995.
5.Pelletier,J.P.etal.:Etiopathogensisofosteoarthritis.Arthritis&AlliedConditions.
ATextbookofRheumatology,14thEd.(W.J.Koopman,ed.).Williams&Wilkins,
Baltimore,MD,2000pp21952245.
6.Lajeunesse,D.:Theroleofboneinthetreatmentofosteoarthritis.Osteoarthritis
Cartilage12(SupplA):S34382004.
7.Heingard,D.etal.:Biochemistryandmetabolismofnormalandosteoarthritic
cartilage.Osteoarthritis.2ndEd.(K.DBrandt,etal.eds.)OxfordUniversityPressInc.,
NewYork,NY,2003pp7381.
8.Garnero,P.etal.:Molecularbasisandclinicaluseofbiochemicalmarkersofbone,
cartilage,andsynoviuminjointdiseases.ArthritisRheum.43(5):9539682000.
9.Khn,K.etal.:Celldeathincartilage.OsteoarthritisCartilage12:1162004.
10.Budsberg,S.C.Managingthepaincausedbyosteoarthritis.Ettinger'sInsightsin
InternalMedicine2:152004.
11.May,S.A.:DegenerativeJointDisease.ManualofSmallAnimalArthrology.
(J.E.F.HoultonR.W.Collinson,eds.)IowaStateUniversityPress,Ames,IA,1994pp
6273.
12.McLaughlin,R.:Managementofchronicosteoarthriticpain.Vet.Clin.NorthAm.
30(4):9339492000.
13.Kealy,R.D.etal.:Effectsofdietrestrictiononlifespanandagerelatedchanges
indogs.JAVMA220:1315202002.
14.Kealy,R.D.etal.:Evaluationoftheeffectoflimitedfoodconsumptionon
radiographicevidenceofosteoarthritisindogs.JAVMA217(11):167816802000.
15.Kealy,R.D.etal.:Fiveyearlongitudinalstudyonlimitedfoodconsumptionand
developmentofosteoarthritisincoxofemoraljointsofdogs.JAVMA210(2):222225
1997.
16.Kealy,R.D.etal.:Effectsofdietaryelectrolytebalanceonsubluxationofthe
femoralheadingrowingdogs.AJVR54(4):5555621993.
17.Kealy,R.D.etal.:Effectsoflimitedfoodconsumptionontheincidenceofhip
dysplasiaingrowingdogs.JAVMA201(6):8578631992.
18.Brown,D.C.etal.:Bodyweightasapredisposingfactorforhumeralcondylar
fractures,cranialcruciaterupture,andintervertebraldiscdiseaseincockerspaniels.
Vet.Comp.Orthop.Traumatol.9:7581996.
19.Millis,D.L.etal.:Caninerehabilitationandphysicaltherapy.W.B.Saunders.
Philadelphia,Pa.,2004.
20.Johnston,S.A.Budsberg,S.C.:Nonsteroidalantiinflammatorydrugsand
corticosteroidsforthemanagementofcanineosteoarthritis.Vet.Clin.NorthAm.27
(4):8418621997.
21.Lascelles,B.D.Main,D.C.:Surgicaltraumaandchronicallypainfulconditions
withinourcomfortlevelbutbeyondtheirs?JAVMA221:2152222002.
22.Budsberg,S.C.etal.:Efficacyofetodolacforthetreatmentofosteoarthritisofthe
hipjointsindogs.JAVMA214(2):2062101999.
23.Vasseur,P.B.etal.:Randomized,controlledtrialoftheefficacyofcarprofen,a

nonsteroidalantiinflammatorydrug,inthetreatmentofosteoarthritisindogs.JAVMA
206(6):8078111995.
24.Holtsinger,R.H.etal.:Thetherapeuticefficacyofcarprofen(Rimadyl)in209
clinicalcasesofcaninedegenerativejointdisease.Vet.Comp.Orthop.Traumatol.
5:1401441992.
25.Dickenson,A.H.:Spinalcordpharmacologyofpain.BritishJournalofAnesthesia
75:1932001995.
26.Woolf,C.J.:Evidenceforacentralcomponentofpostinjurypainhypersensitivity.
NatureMed.306:6866881983.
27.Urban,L.etal.:Modulationofspinalexcitability:cooperationbetween
neurokininandexcitatoryaminoacidneurotransmitters.TrendsNeurosci.17
(10):4324381994.
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