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ManagingDJD:

theNSAIDSMattBrunke,DVM,CCRP,CVPP,CVAACVSMRCareerPathCandidate

GarretPachtinger,VMD,DACVECC

COO,VETgirl

Introduction

JustineA.Lee,DVM,

DACVECC,DABTCEO,VETgirl

Introduction

• Thetech-savvywaytogetonlineveterinaryCE!• Asubscription-basedpodcastandwebinarserviceofferingveterinaryRACE-approvedCE

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Videoarchives On-demandvideo

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Cecertificates

• MattBrunke,DVM,CCRP,CVPP,CVA

• ACVSMRCareerPathCandidate

Speakerintroduction

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Alittleaboutme…..Iliketokeepbusy

HowmanyofyouseeDJD/OA?

• CCLDz• HipDysplasia• ElbowDysplasia• OCD• Trauma• Athletic/WorkingCanines• Obesity• Conformationissues

Osteoarthritisisthe#1CauseofChronicPaininDogs

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1.GaynorJetal.TheEssentialGuidetoPainManagement:AcompleteResourceforVeterinaryPainManagement2003.2.JohnstonSA.VetClinNAmSmallAnimPract27:699-723;1997.

• Chronicpain

• Decreasedactivity

• Anoverallnegativeimpactonthepatient

• Interfereswithhuman-animalbond

• Decreasedfoodintake

• Euthanasiafordogsthatbecomenon-responsivetotreatment

Impact

Affects20%ofDogsinU.S.

WhenareyoufindingOA/DJDpatients?

• Everyexamyoudo!– DOGSandCATS• Especiallygeriatrics – ageisNOTadisease• Knowyournormal– flex/extendeverypatient• History?’s– troublewithstairs?Lessactive?• Feelfor:jointthickening,musclewasting,decreasedelbowflexion,decreasedhipextension

• Lookfor:scuffmarksonnails,poorposture,swayback,unevenpadwear

• CartilagedamageoccursWAYbeforeradiographicchanges

PathophysiologyofOA/DJDinvolvestheentirejoint

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CartilagedamageinitiatesOA/DJD• Initialtrauma=fibrillationofcartilagesurface,damagetochondrocytes,releaseof:

• Cartilagedegradationproducts(CDPS)

• Matrixmetalloproteinases(MMPs)• Nitricoxide(NO)andinflammatorycytokines

• MMPs/CDPSareengulfedbysynoviocytes,whichrelease:

• Inflammatorymediators:PGE2,TNF,IL1b andMMPs

• Allcontributetocycleofinflammation,degradationandpainofosteoarthritis

InitialCartilageDegradation

EndStageCartilageDegradation

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OtherChangesinOA/DJD

• ThickeningofJointCapsule• Remodelingofsubchondralboneè sclerosis• Osteophyteformation

• SynoviocytesreleaseBoneMorphogeneticProteins(BMPs)• Periosteummesenchymalstemcelltodifferentiateintochondrocytes• Initiateosteophyteformationè jointmouseorimpingeonperiosteum

• Bottomline:OAbecomesaviciouscycle• Jointislessabletobearstressandforces:

• Furtherjointdamage• Clinicalsigns

Pro-inflammatoryMediatorsCauseProgressiveJointDamage

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1.PelletierJPetal.ATextbookofRheumatology,KoopmanW(ed).14thEd:2195-2245.Lippincott,WilliamsandWilkins;Baltimore,2000.

2.CleggPDetal.EquineVetJ.29:335-342;1997.3.Martel-Pelletieretal.FrontiersinBioscience4:D694-D703;1990.

Pro-inflammatoryMediators• PGE2• IL-1,IL-6,TNFMatrixMetalloproteinases

SynoviocytesReleasePro-inflammatorymediators(TNFandIL-1b)MMPs

Pro-inflammatoryMediatorsCauseProgressiveJointDamage

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1.PelletierJPetal.ATextbookofRheumatology,KoopmanW(ed).14thEd:2195-2245.Lippincott,WilliamsandWilkins;Baltimore,2000.

2.CleggPDetal.EquineVetJ.29:335-342;1997.3.Martel-Pelletieretal.FrontiersinBioscience4:D694-D703;1990.

OngoingInflammationistheSourceofBoththeProgressiveNatureandPainofOsteoarthritis

• ProstaglandinE2(PGE)andotherinflammatorycytokinesleadto:• Progressivedegradationofthejoint• Stimulationofnociceptorsinsynovium,jointcapsuleandsubchondralbone

• PGEisalsoreleasedindorsalhornandcontributestothepainsignal

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JohnstonSA.VetClinNA,SAP,31:39-53:2001.

JointInflammationisOneSourceofPaininOA/DJD

• Cartilageisanueral;cartilagedamagealoneisnotpainful• Inflammationstimulatesnociceptorsfoundin:

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• Thejointnociceptorsinitiatepathologicalpain

JointCapsule Synovium

SubchondralBone Periosteum

NeurogenicInflammation

• Isanadditionalstepinthenociceptivepathway• Involvetheantidromic releaseofneurotransmittersnearthejoint• NeurotransmitterssuchasSubstancePè inflammatorymediatorswithinthejoint

• Contributestojointpainandinflammation

1.JohnstonSA.VetClinNA,SAP,31:39-53;2001.2.CoutauxA,etal.JointBoneSpine.,72:359-371;2005.

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Pro-inflammatorymediatorsinitiatepainandhyper-sensitizetheCNS

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1. CamuF,Shil,VanlersbergheC.Drugs.63Suppl1:1-7;2003.2. JohnstonS.VetClinicsofNA:SmallAnimalPractice,31:39-53;2001.

1.Johnston,SA.VetClinNAmSmallAnimPract27:699-723;1997.2.CamuF,etal.Drugs.63Suppl1:1-7;2003.3.MuirWW.VeterinaryPainManagement,Gaynor,JandMuirWW.(Eds),Mosby,Columbus2003.

SummaryofInflammatoryProcessofOA

• OAisachronicprogressivelydestructivediseasethatinvolvestheentirejoint• Inflammationisakeycomponentofbothjointdestructionandpain• Acutepainresolvesaftertheinitialinjuryheals• Chronicpaininvolvesstructuralchangesofthedorsalhorn,ismoreintensethanacutepain,andmoredifficulttocontrol

• TreatmentconsiderationsforOAshouldaddressinflammationaswellaspain

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Multimodalapproach NSAIDisthecornerstoneoftherapy

• Quickaction• Anti- “itis”

• Butwhathappenswhen:• Ownerdeclinesit?• Patientcan’ttakeit?• It’snotworking?• Wehavelostthepharmacy?

NutritionOptions/Goals

• Minimizeobesity• Keepupproteininseniorpets–keepmusclemass

• FortifiedwithOmega-3’s

Obesity– aheavyissue

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ObesityEffects- Two-fold

• Biomechanicalstresscontributestoclinicalsignsandprogressionofdisease

• Adipokinessecretedbywhitefatcellscontributetotheprogressiveinflammationofosteoarthritis

• Leptinlevelsareelevatedinobesedogs• Inhumanswithosteoarthritis,increaseleptinlevelscorrelatewithelevatedMMPsandNOinsynovialfluid

• Adiponectinisanti-inflammatory,butlevelsarelowinobesedogs

• Inhumanpatientswithkneeosteoarthritisthereisasignificantcorrelationwithadiponectin:leptinratios 1.CicuttiniFM,etal.JRheumatol.1996;23:1221-1226.

2.TodaY,etal.Rheumatol.1998;25:2181-2186.3.Marshalletal.VetCompOrthoTraumatol2009;5:339-345.

EffectsofweightlossonOA

• Humanswithincreasedbodymassindex(BMI)experienceOAinnon-weightbearingjoints,whichresolveswithweightloss

• DecreaseinBMI,isassociatedwithsymptomaticrelieffromkneeOAinman• Systematicreviewofcaninestudiesfound

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PreventingObesityDecreasesIncidenceofOA

WeightLossReducesSignsofOA

Omega-3dietsindogs Andcats!

Nutritionalsupplements

• Glucosamine• Chondroitin• MSM• ASU• More?• Atalkforanotherday

Rehabilitation(PhysicalTherapy)

PhysicalModalities • Therapeuticlaser,ultrasound,TENS,etc.

ManualTherapies• Jointmobilization• Massage• ROM,stretching

TherapeuticExercise– CoreofPT

• Corestrengthening• Weightbearing• Proprioception• Underwatertreadmill

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GoalofRehabilitationwithOA

BuildMuscleSupportAroundJoint

ReducePain

WeightLosswhenindicated

Maintain/ImproveMuscleMass

ReachingGoalswithRehab

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• Athometherapies

• In-clinicrechecksandtherapy

• Concurrentpainmanagementshouldbeconsideredaspartoftherehabilitationprogram

ProgramCanThenBeTailoredtoIndividualPatient

• Beginwithpatientassessment

– Determinemobilitystatus,limbgirth,rangeofmotion

– Assessbodyconditionscore

DeterminingGoal

Thermotherapy

Becreative.DON’TUSEELECTRIC HEATINGPADS.

LightAmplificationbyStimulatedEmissionofRadiation• Photobiomodulation• Activatecytokinesandothertissuefactors

• Decreasepainandinflammation• Increasewoundhealing• Alwaysusegoggles• Canuseinacupuncture• Notoncancerorpregnancy• AnotherlectureJ

ManualTherapy

• Skilledhandmovementtechniquesintendedto:• Improveissueextensibility

• IncreaseROM

• Inducerelaxation

• Mobilizeormanipulatesofttissuesandjoints

• Modulatepain

• Reduceswellingandinflammation

TherapeuticExercises

• Theoccupationaltherapyaspectofrehab• Buildongoingfromdowntoup,andthenmimickingthefunctionsneededtobeinanormalenvironment

• Returntofunction

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Cavaletti Rails Peanuts

BalanceBoardandRolls

• Corestrength- Yoga• Makesuregoodtraction• Useyourweighttohelpshift• Candojustfrontlimbsorhindlimbs

• Rhythmicstabilization

CoreStrengthening

Walking

• Agreatexercise• Onleash,continuousmovement– flatnon-slipsurfaces

• Atapaceappropriateforthepatient,nottheowner

• Startwith10-12minutestwiceaday,increaseeachweekby3-5minutes

• Addinhills,varyingtraction(sand,snow,highgrass)

Hydrotherapy– anotherpresentation

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Treadmills

• Diagnostictoolalso• Safeandcontained• Feetalwaystouchingground• Buoyancy• Takesafewseconds/minutetogetthemusedtoit

Polysulfated Glycosaminoglycan• FDAapproved,diseasemodifyingosteoarthritisdrugs;fordogsandhorses;water-based,forintramuscularInjection

• Dosage:2mg/lbbodyweight,IM,twiceweeklyforupto4weeks(maximumof8injections)

• MOA:specificisnotknown;invitrostudiesshow;• Inhibitserineproteinases;PGE2synthesis;metalloproteases,hyaluronidasesandothers

• Stimulatesynthesisofprotein,collagen,proteoglycans,andhyaluronicacid• Anecdotally“maintenance”injectionsmonthly• OfflabelSQusage• OfflabelfelineSQusage

• 1.Adequanprescribinginformation.NADA 141038,NovartisAnimalHealth,US,INC.

PolysulfatedGlycosaminoglycan–ClinicalStudies

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• Treateddogshadstatisticallysignificantimprovementinrangeofmotionandtotalorthopedicscoreoverplacebotreatedcontroldogs

Efficacy

• 2.1%ofdoghadadversereactionsincluding– Transientpainattheinjectionsite(1incident)– Transientdiarrhea(1incidenteachin2dogs)– Abnormalbleeding(1incident)– Theseeffectsweremild,self-limiting;didnotrequireinterruptionof

therapy

Safety

• DonotuseindogsshowinghypersensitivitytoPSGAG,orindogswithknownorsuspectedbleedingdisorders

• Usewithcautionindogswithrenalorhepaticimpairment

OtherDiseaseModifyingOADrugs(DMOAD)

• Zydax – Pentosan• Parnellproduct,availableinAustralia,maybecomingtotheUS

• Potentialbenefitforhorses• Noevidenceindogscurrently

AdjunctAnalgesics• UseinadditiontoorasareplacementforNSAIDS• Amantadine– onlydrugstudiedtotreatcanineosteoarthritis

• IndogswithosteoarthriticpainrefractorytoanNSAIDs,additionofamantadineimprovedphysicalactivity

• Mightbeausefuladjuncttherapyfortheclinicalmanagementofcanineosteoarthriticpain.

• 3-5mg/kgSID,catstoo

• Gabapentin– Calciumchannelmodulator– catsanddogs• 5-10mg/kgSID-TID

• Amitriptyline– SSRI– norepinephrine- catsanddogs• 0.5-1.0mg/kgSID-BID

• 1.LascellesBDX,etal. JVetInternMed.22(1):53-9,2008.

MoreAdjunctAnalgesics

• Acetaminophen– dogsnotcats.• 10-15mg/kgTID(bridgedrug)

• Localanesthetics– Lidocaine,bupivacaine,mepivacaine• Opioids– morphine,meperidine,methadone,oxymorphone,hydromorphone,fentanyl,fentanylpatches,butorphanol,pentazocine,nalbuphine,buprenorphine,codeine

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Tramadol• Metabolismandeliminationisrapidandvariableamongdogs• Whenadministeredorallyorintravenouslytothedog,metabolismoftramadolandallmetabolitesisrapid

• Thereismuchvariabilitybetweendogs,possiblybreeds• Paincontroldidnotnecessarilycorrelatewithplasmalevelsoftheactivemetabolite(O-desmethyltramadol)

• Affectsona-adrenergicorserotoninreceptorsmaycontributetoanalgesiceffectsinthedog

• Regardlessofmechanismofaction,studiessuggestoraldoseshouldbe5mg/kgq6hoursor2.5mg/kgq4hours

• AdditionallystudiesforaffectsincanineOAareneeded• 1.KukanichB,PapichMG.JVetPharmacolTherap.27,239-246:2004.

• 2.GiorgiMetal.VetResCommun33,875-885:2008.

• 3.KukanichB,PapichMG.AJVR.72,256-262;2011.

WhatisGALLIPRANT®(grapiprant tablets)?

• Galliprant isafirst-in-classnon-cyclooxygenase(COX)inhibiting,non-steroidalanti-inflammatorydrug(NSAID)inthepiprant class.

• Piprants areanewlyrecognizeddrugclass,establishedanddefinedbytheWorldHealthOrganizationin2013asprostaglandinreceptorantagonists(PRA).

• UniquemechanismofactionbyantagonizingtheprostaglandinE2(PGE2)EP4receptor.• PGE2itsphysiologiceffectsthroughbindingoffourdifferentreceptors,EP1,EP2,EP3andEP4.

• EP4receptorhasbeenidentifiedastheprimaryreceptorresponsibleformediatingpainandinflammationassociatedwithosteoarthritis.GALLIPRANTselectivelyblockstheEP4receptor,thusblockingPGE2elicitedpain.

Aratana - Galliprant® ESWT– ExtracorporealShockWaveTherapy• Shortdurationacousticwavesatlowfrequencyandhighpressure

• 100xatmosphericpressure inmicroseconds• Mechanismslacking– butreported

• reducedinflam/shorttermanalgesia• improvedvascularity,neovascularization• increaseboneformation• realignmentoftendonfibers• enhancedwoundhealing

• ImprovedweightbearingandcomfortableROMsimilartoNSAIDs

• Heavysedationoranesthesiausuallyrequired• Repeatingtreatmentq2-3weeksfor3-4treatments

• NoconcurrentNSAIDS

ESWTResearch ESWTResearch

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PEMF- PulsedElectromagneticFieldTherapy PEMF- PulsedElectromagneticFieldTherapy

PEMFResearch- Human PEMFResearch- Human

TCVM– TraditionalChineseVeterinaryMedicine

• Acupuncture• Electro– mostpublisheddata

• HerbalTherapy• FoodTherapy

Electroacupuncture forpain

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KinesiologyTaping

• Worksonlifting• Improvebloodflow,lymphaticreturn

• Painmitigation• Inflammation• Neurosensoryawareness

KinesiologyTaping– PainofOA/DJD MoreResearch

Intraarticular injections– TargetedTherapy

• Easytolearn• Sedated• Radiographs– verifythedisease• SterilePrep

IAInjections- Options

• Corticosteroids• HyaluronicAcid• RegenerativeMedicine

• PlateletRichPlasma(PRP)• StemCellTherapy

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IAInjections- Corticosteroids

• (20mg)ofmethyl-prednisoloneacetate

• Triamcinolone– 0.22mg/kgtotal

• Lesssystemiceffectswithtriamcinolone

IAInjections- HyaluronicAcid

• Increaseviscosityofjointfluid• Anti-inflammatory• Analgesic• Induceproductionofsynovialfluid

• Manydifferentoptions• Molecularweight

• Combinewithsteroid?

HA-article IAInjections– RegenerativeMedicine

• In-clinicandoutsideoptions• In-clinic– samedayharvestandtreatment,singleanesthesia

• Outside– culture,banking.• Buttwoanesthesiaepisodes

IAInjections– RegenerativeMedicine- PRP

• PlateletRichPlasma• 60ccofblood– 4ccofplatelets• Positiveeffectsonangiogenesisandextracellularmatrixremodeling

• Fibrinformatrix• Growthfactors–VEGF,TGFB,IL8• Cellproliferationanddifferentiation

• Stemcellrecruitmentandchemotaxis

Whichdoweuse?

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IAInjections– RegenMed– StemCells

• BoneMarrowvs.Adipose?• Contributetogeneratingnewtissue

• Chemotacticforprogenitorcells• Supplygrowthfactors• Makeextracellularmatrix• Angiogenesis• Anti-apoptosis• Anti-inflammatory• Anti-fibrotic

StemCellResearch

RecentResearch PromisingResults

TreatmentIA• MildOAandsynovitis

• HAweeklyx3weeksorsinglePRPinjection

• NoresponsetoHA,singlePRPinjection

• Acutepost-op(8-12weeks)• HAweeklyx3weeksorsinglePRP• IfnoresponsetoHA,singlePRPinjection

• ModerateOA• PRPinjectionweeklyx2injections(repeatifneeded)

• IfnoresponsecombinationMSC/PRP

• SevereOA• PRPeveryotherweekfor2-3treatments

Or• MSC/PRPcombinationfollowedbyboosterinjectionin9-12months

Or• IAsteroid

• 1injectionfollowedbya2nd ifneededin3-4weeks(maxof4injectionsperyear)

CopyrightS.Canapp 2017

TreatmentIA

• Expecteddurationoftreatment:• HA- 6monthsofrelief

• 80%respondwell• 10%respondfair• 10%don’trespond

• PRP- 9-12monthsofrelief• PRP/MSC- 18-24monthsofrelief

• Postregenerativemedicinetreatment• Noshockwavetx• Nolasers(4weeksforcells,2wks PRP)• Nocoldorwarmpacks• Noultrasoundtherapy• NoNSAIDS

• 8weekswithMSCorPRP/MSC• 2weekswithPRPtx

Copyright2017

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WhattechniquesdoIuse?

• Alloftheoneswejustmentioned!

• Iadjusttomypatient’sneeds,client’sneeds/wants

• IofferwhatIwoulddoifitwasmypet!

Evenmoreoptions

• Botulinumtoxin• Monoclonalantibodyfornervegrowthfactor– dogsANDcats• Undenatured TypeIICollagen• RadiationTherapy

Summary

• Treatearly– beproactive,notreactive• Don’twaituntilseverecartilagedamage• Weightlossandexercisearecrucialinallstages• Multimodalapproach• Includepainmanagement

UpdatedGuidelines

• https://www.aaha.org/public_documents/professional/guidelines/2015_aaha_aafp_pain_management_guidelines_for_dogs_and_cats.pdf

Thankyou ContactInfo

• Email:drmattbrunke@gmail.com• DrBrunke.wordpress.com• Cell(notforclients)518-470-7586• Office:VOSM– VeterinaryOrthopedicsandSportsMedicine• VOSM.com

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