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© 2018 Journal of Natural Science, Biology and Medicine | Published by Wolters Kluwer - Medknow180
Original Article
IntroductIon
Painisthemostcommoncomplaintinosteoarthritis(OA),whichrestrictsthephysicalactivityofthepatientsaswellasdecreasesworkperformance.[1]InOAoftheknee,painmayarisefromperiostealelevation,trabecularmicrofractures,capsulardistension,and/orsynovialinflammation.Factorscomplicating determination of the source of painmayincludevarusorvagusdeformity,weight issues, and theemotionalimpactofchronicpain.Oncethecauseofpainis identified, treatment plan can be formulated.[2] Painis themost common reason in patientswithOA to seekmedicalhelp.[3]ThecurrenttreatmentstrategiesforOAaimtoeducate thepatientaboutOA,alleviatepain,optimizeandmaintain joint function and prevent or suppress theprogressionofadversestructuralchangeaffectingthejointtissues.[4]
Commonlyusedpharmacologicalagentsforpainmanagementare nonsteroidal anti‑inflammatory drugs (NSAIDs).[5]Most of the patientswithOA takemedication for a longperiodandhaveanumberofcomorbidities,whichrequiresconcomitantmedication,increasingthelikelihoodofadverseevents includinggastrointestinal (GI) injury.[6]There is anincreasingdemandformoreeffectiveandsafertreatmentforOA.PiroxicamisanNSAID,anoxicamderivative,whichareenolicacidsthatinhibitcyclooxygenase(COX)enzymenon
A Comparative Study of Efficacy and Safety of Piroxicam and Naproxen in the Management of Pain in Osteoarthritis of the
KneeYaseen Mohammed, Sarala Narayana, H. S. Arun1
Departments of Pharmacology and 1Orthopaedics, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka, India
Introduction: Osteoarthritis(OA)isadegenerativejointdiseaseandcauseforfunctionaldisability.OAischaracterizedbytheinsidiousonsetofpainandlimitedrangeofmovements.PiroxicamandnaproxenareusedinOA,rheumatoidarthritis,acutegoutyarthritis,migraine,dysmenorrhea,andpostoperativepain.TheaimofthisstudywastocomparetheefficacyandsafetyofthesedrugsinpatientswithOAoftheknee.Materials and Methods:Thiswasarandomized,open‑label,comparative,parallelgroupstudyconductedinpatientswithOAofkneejoints.Theyreceivedeitheroralpiroxicam20mgornaproxen500mgtwicedailyfor6weeks.ThepainwasassessedusingVisualAnalogScale(VAS)andWesternOntarioandMcMasterUniversitiesArthritisIndex(WOMAC)scoresatbaseline,2nd,4th,and6thweek.Patientsatisfactionscore(PSS)andqualityoflifewereassessedatfollow‑up.AdverseeffectswereassessedusingtheWorldHealthOrganizationcausalityscale.Descriptiveandinferentialstatisticswereused. Results:Atotalof110patientswererecruited,47malesand63females,100completedthestudy(51inGroupPand49inGroupN).BothpiroxicamandnaproxensignificantlyreducedVASandWOMACscoresatthe2nd,4th,and6thweek(P=0.001)comparedtobaseline,butthiswasnotsignificantbetweenthegroups.PSSwassignificantly(P=0.03)highat4thand6thweekwhencomparedtoweek2withbothmedications,butbetweenthemedications,itwasinsignificant(P=0.10).Theadverseeffects suchasepigastricdiscomfort,nausea,andvomitingwereobservedwithboth thedrugs,but itwasmorewithnaproxen.Conclusion:Piroxicamwasaseffectiveasnaproxeninrelievingpainandimprovingtherangeofmovementswithlessadverseeffects.
Keywords:Kneejoints,naproxen,osteoarthritis,piroxicam
Address for correspondence: Dr. Sarala Narayana, Departments of Pharmacology, Sri Devaraj Urs Medical College,
Sri Devaraj Urs Academy of Higher Education and Research, Tamaka, Kolar, Karnataka, India.
E‑mail: [email protected]
Access this article online
Quick Response Code:Website:www.jnsbm.org
DOI:10.4103/jnsbm.JNSBM_154_17
Abstract
How to cite this article: MohammedY, Narayana S,Arun HS.Acomparativestudyofefficacyandsafetyofpiroxicamandnaproxeninthemanagementofpaininosteoarthritisoftheknee.JNatScBiolMed2018;9:180‑4.
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Mohammed, et al.: Mohammed et al Piroxicam and naproxen in osteoarthritis
Journal of Natural Science, Biology and Medicine ¦ Volume 9 ¦ Issue 2 ¦ July-December 2018 181
selectively.Itresultsininhibitionofprostaglandinproduction,whichisthemainmediatorofpain.Ithasalonghalf‑life(t½)ofapproximately50handavailableasoralformulation,andhence, it is suitable for use inOA.[5] It is also used in themanagementofpostoperativepain,musculoskeletaldisorders,anddysmenorrhea.[7]IthasshownclinicalefficacyinrelievingpainassociatedwithOAandrheumatoidarthritis,especiallywhere there is an associated inflammatory component.[8] Italso suppresses primary and secondary lesions of adjuvantarthritis.[9]NaproxenisanNSAID,apropionicacidderivativeandisanonselectiveCOXenzymeinhibitor.Itiswell‑absorbedorallyandhasat½of14h.[5]Ithasclinicallyprovenefficacywithregardtoanalgesiaandreliefofmorningstiffness.[10]Ithassideeffectssuchasabdominalpain,gastritis,drowsiness,nausea,vomiting,dizziness,andpruritis.
mAterIAls And methods
A randomized, open‑label, comparative, parallel group,prospectivestudywasconductedinpatientsdiagnosedwithOAofkneejoints.ThisstudywascarriedoutbytheDepartmentsofPharmacologyandOrthopaedicsinR.LJalappaHospitalandResearchCentreattachedtoSriDevarajUrsMedicalCollege,Tamaka,Kolar,fromJanuary2015toJune2016.Patientsofeithergender,agedbetween40and70yearswithsymptomaticidiopathicOAofbilateralkneejointinvolvementforaminimumperiodof6months,radiologicalevidenceofOAofkneejointsandmorning stiffnessof<30mindurationwith crepitusonmotionwere included in the study.Exclusioncriteriawere:patientswithahistoryofsurgeryoracutetraumatothekneejointwithin6months,historyofpepticulcer,GIbleeding,psychiatricillness and bronchial asthma, acute inflammatory arthritis,pseudogout, or severe osteoporosis, thosewith derangedhepaticorrenalparametersandalsowhowerehypersensitivetopiroxicamornaproxen.PatientswithpainduetoOAofkneejointswererecruited,randomizedbysimplerandomizationina1:1ratiointotwogroupsof55each,withGroupPreceivingpiroxicam20mgandGroupNreceivingnaproxen500mg,bothmedicationsgivenorallytwicedailyfor6weeks.Patientswerefollowedupat2nd,4th,and6thweek.Thepatientsrecruitedinbothgroupswerematchedintermsofage,gender,weight,andbodymassindex(BMI).Theywereinstructedtoperformthemildexercise(kneeflexionandhamstringstretch),applyhotfomentation,anduseIndianstyletoilet.
Demographicdetailsandrelevanthistorywerecollectedfromthepatientat the timeof recruitment.Clinicalexaminationincluding general physical examination and knee jointsexamination(inspection,palpation,therangeofmovementsandmeasurements) was performed. Routine laboratoryinvestigations such as complete hemogram, randombloodsugar,bloodurea,serumcreatinine, liver function test,andurine routinewere carried out at baseline.X‑rays of kneejointsweretakenatbaselinefordiagnosis.Rheumatoidfactorwasdonewhenrequired.TheVisualAnalogScale(VAS)[6]andWesternOntario andMcMasterUniversitiesArthritisIndex (WOMAC)[1] scoreswere assessed at baseline and
at each follow‑up.TheVAS scorewas graded from 0 to10accordingtopatient’sresponse.WOMACisasubjectivescoreconsistingofsubscalesintermsofpain,stiffness,andphysicalfunction.Alltheparametersweregradedonascaleof0–4dependingontheseverity,fromnonetosevere.ThereductioninWOMACscoreindirectlyindicatesimprovementin thequalityof life(QOL).If theVASscorewas>3afterinitiatingthetreatmentwithstudydrugs,oraltramadol50mgwas used as rescue analgesic. Patients’ satisfactionwithrespecttopainreliefwasassessedusingpatient’ssatisfactionscore(PSS)ateachfollow‑up.PSSwasgradedas1=poor,2=fair,3=good,and4=excellent.Duringthefollow‑up,thesafetyofthedrugswasmonitoredusingtheWorldHealthOrganizationcausalityscale.
Statistical methodsTodetectameandifferenceofVASscoreof0.98attheendof1monthwithaneffectsizeof0.564,powerof80%,alphaerrorof5%,anddropoutrateof10%,therequiredsamplesizewas55patientspergroup.Thedemographicdatawereanalyzedusingdescriptivestatistics.TheVASandWOMACscoreswereassessedusingrepeatedmeasureanalysisofvariancefollowedbyBonferroniposthoc testwithin thegroup andunpairedt‑testbetweenthegroups.AdverseeventswereanalyzedusingChi‑squaretest.Patient’ssatisfactionscorewasanalyzedusingWilcoxonandMann–WhitneyU‑test.QOLwasanalyzedusingdescriptivestatistics.Thevalueof P <0.05wasconsideredasstatisticallysignificant.
results
PatientswithOAofboththekneejointsrecruitedwere110but100patientscompletedthe6weeksstudyperiod[Figure1].Theanalysiswasperformedforpatientswhohavecompletedthestudy.Thedemographicparameterssuchasage,gender‑wisedistribution,BMI,andoccupationwerecomparableinboththegroups.Among110patients, themajorityofpatientsinbothgroupswerefemales(57.3%).Housewivesconstitutedfor>40%inboththegroups[Table1].
TheVASscorewithinthegroupsandbetweenbothmedicationsisrepresentedinTable2.
ThereductioninmeanVASscorewasstatisticallysignificantateachfollow‑upcomparedtobaselineinbothgroups(P=0.001).Byweek6,therewassignificant(P=0.001)decreaseinVASscorewithboththemedications.ThereductioninmeanVASscorewasnotsignificant(P=0.20, P =0.81, P =0.38)betweenthetreatmentsatanypointoftime[Table2].Theareaunderthecurveforareductioninpaininpatientsreceivingmedicationsin both the groups [Figure 2]was calculated by trapezoidmethod.Thedecreaseintheareaoftrapezoidoveraperiodindicatesthereducedintensityofpainwithbothmedications.Whenthisareawascomparedbetweenmedications,itwaslesswithpiroxicam(5.33)comparedtonaproxen(5.45)atweek6.
TheWOMAC scorewithin the groups and between bothmedicationsisrepresentedinTable3.Thereductioninpain,
Mohammed, et al.: Mohammed et al Piroxicam and naproxen in osteoarthritis
Journal of Natural Science, Biology and Medicine ¦ Volume 9 ¦ Issue 2 ¦ July-December 2018182
stiffness, and physical function scoreswere statisticallysignificant (P = 0.001) atweeks 2, 4, and 6 compared tobaselinewith both themedications [Table 3]. Based onthe physical function subscale ofWOMAC, reduction inscoreindicatesgradualimprovementintheQOLat2nd,4th,and6thweek.When the scoresof subcaleswere comparedbetween groups, the reductionwas insignificant at eachfollow‑up.ThereductioninWOMACscorewasstatisticallysignificant (P = 0.001) atweeks 2, 4, and 6 compared to
baselinewithboththemedications.Morethan75%decreaseinthescorewasobservedatweek6.ThereductioninmeanWOMAC scorewas insignificant between piroxicam andnaproxenatallthefollow‑upvisits.
Inpiroxicamgroup,64.7%ofpatientsgradedtheirsatisfactionas good at both 4th and 6thweek.Nearly 5.9%of patientsexpressed their satisfaction as excellent atweek 6.ThisincreaseinPSSatbothweekswasstatisticallysignificantascomparedtoweek2(P=0.03).At4thweek,60.7%ofpatientsgradedtheirsatisfactionasgood,whereas63.2%at6thweekingroupN.PSSwassignificantlyimprovedat4thand6thweekcompared toweek 2with naproxen (P = 0.03). PSSwasinsignificantbetweenthemedications(P=0.10)[Figure3].Adverseeffectswithpiroxicamandnaproxenwereepigastricdiscomfort(19.2%vs.32%),nausea(15.3%vs.18.8%),andvomiting(15.3%vs.24.5%).Thesesymptomsweretreatedwithomeprazole20mgoncedailytilltheysubsided.
dIscussIon
OA is one of the most common degenerative diseaseparticularlyaffectingthekneejoints,anditisthemajorcause
Table 1: Comparison of demographic parameters between Group P and Group N
Variables Group P (n=55) Group N (n=55)Age(years),mean±SD 55.24±9.80 52.03±9.00Male/female 23/32 24/31BMI(kg/m2),mean±SD 25.80±4.32 26.00±4.57Housewife 24 22Farmer 16 18Teacher 8 9Tailor 7 6BMI:Bodymassindex,SD:Standarddeviation
Figure 1: Consort flow chart representing recruitment, randomization and follow‑up
Mohammed, et al.: Mohammed et al Piroxicam and naproxen in osteoarthritis
Journal of Natural Science, Biology and Medicine ¦ Volume 9 ¦ Issue 2 ¦ July-December 2018 183
of disability in elderly.OA is a disease of synovial jointscharacterizedbyinflammationofthejointcapsule,cartilagelossalongwithperiarticularbonedamage.Itisassociatedwithpain,impairedmuscularstability,reducedrangeofmovement,andfunctionaldisability.OArarelyoccursbeforetheageof
40yearsbutby75yearsatleast85%ofthepopulationhaveeitherclinicalorradiographicevidenceofthedisease.OAisanappropriatemodeltoassesstheefficacyofnewanalgesicsatrepeateddoses.[5]NSAIDsarewidelyusedforthetreatmentof pain in patientswithOA.However, they are associatedwithadverseeffectsmainlyGI,suchasepigastricdiscomfort,dyspepsia,abdominalpain,nausea,andvomiting.Thus,thedecisiontoprescribeNSAIDsisbasedontheireffectivenesstoreducepainwithlessadverseeffects.
In thepresent study,110patientsdiagnosedwithmoderateto severeOA of both the knee jointswere recruited andrandomizedasshowninFigure1.Theyreceivedpiroxicam20mginGroupPornaproxen500mgingroupNtwicedailyfor6weeks.Onehundredpatientscompletedthestudyperiod.Mostofthepatients(70%)wereinthefifthdecadeoflifewhichsubstantiatesthatOAoccurrenceincreasesasageadvances.Someof thefactorscontributing toOAinelderlycouldbedegenerativechangesinthemenisci,jointligaments,increasedboneturnoveraswellascalcificationofjointtissues.[11]
Thefemalepatientsweremoreinboththegroups.AstudybyRugstadetal.,comparingpiroxicam20mgwithnaproxen750mgoncedailyinOAofthekneealsohadmorefemalepatients.[12]Thiscouldbebecauseinwomen,tendonsaremoreelasticandkneejointsarenotalignedstraightasinmenwhichleadtoinjuriesandmaymanifestasOAinthelaterpartoftheirlife.Inaddition,femalepatientswhosemothershadOAmightdevelopthisdiseaseinthesamejointandatthesameage.Estrogenprotectscartilagefrominflammation,butduringandaftermenopause,thedecreasedestrogenlevelleadstohighriskofOA.[13]Obesitycontributes toextra stressonknees,whichleadstocartilagebreakdown,andinthisstudy,mostpatientswereoverweight.
WeobservedthatbothpiroxicamandnaproxensignificantlyreducedtheVASscoresat2nd,4th,and6thweekcomparedtobaseline[Table2].Thereduction inpainwassignificant inpatientsreceivingeithermedication,andalsotherewasagoodclinicalresponse.Betweenthegroups,reductioninVASscorewasnotstatisticallysignificantatanyofthefollow‑upvisits.InastudybyRichyetal.,piroxicamwassimilarinefficacycomparedtootherNSAIDsinreducingpaininpatientswithOAoftheknee.[14]Allegrinietal.havereportedthatpiroxicam
Table 3: Comparison of subscales of Western Ontario and McMaster Universities Arthritis Index within and between the groups at all evaluation points
Mean±SD P (between groups)Group P Group N
PainsubscaleBaseline 13.25±2.25 13.27±1.95 0.422ndweek 09.92±1.74* 09.81±1.62* 0.364thweek 07.03±1.34* 07.00±1.41* 0.286thweek 04.35±0.82* 04.41±0.86* 0.17
StiffnesssubscaleBaseline 04.73±0.50 04.58±0.53 0.262ndweek 03.51±0.50* 03.55±0.54* 0.414thweek 02.51±0.50* 02.55±0.54* 0.746thweek 02.00±0.00* 02.02±0.14* 0.32
PhysicalfunctionsubscaleBaseline 39.63±3.34 39.56±2.92 0.542ndweek 29.66±3.57* 30.40±2.85* 0.404thweek 19.47±3.08* 20.07±3.25* 0.126thweek 09.52±2.28* 09.89±1.99* 0.20
*P=0.001whencomparingtheevaluationpointswithbaseline.SD:Standarddeviation
Table 2: Comparison of mean visual analog scale scores within and between the groups at all evaluation points
Mean±SD P (between groups)
Group P Group NBaseline 8.00±1.51 7.78±1.45 0.402ndweek 5.52±1.35* 5.45±1.32* 0.204thweek 3.53±1.10* 3.55±1.12* 0.816thweek 1.80±0.70* 1.90±0.60* 0.38*P=0.001whencomparingtheevaluationpointswithbaseline.SD:Standarddeviation
Figure 3: Patient’s satisfaction scoreFigure 2: Area under curve – piroxicam and naproxen
Mohammed, et al.: Mohammed et al Piroxicam and naproxen in osteoarthritis
Journal of Natural Science, Biology and Medicine ¦ Volume 9 ¦ Issue 2 ¦ July-December 2018184
patchwaseffectivecomparedtoplaceboinreducingpainduetoOAofthelumbarvertebra.[15]Alhoetal.studyshowedthatpiroxicamandnaproxenweresimilarinefficacywhenusedforOAofthehipjoint.[16]Inthisstudy,theintensityofpainexperiencedbythepatientsover6weeksisrepresentedbytheareaunderthecurveandthosereceivingpiroxicam(5.33)hadmarginallybetterpainreliefcomparedtonaproxen(5.45)atweek6asshowninFigure2.
The parameters ofWOMACdepicting pain, stiffness, andphysicalfunctionweresignificantlyreducedinbothgroupsateachfollow‑upcomparedtobaseline[Table3].Inthisstudy,boththedrugssignificantlyreducedWOMACscoreat2nd,4th,and6thweekcomparedtobaseline.ReductioninWOMACscoreimpliesareductioninpain,improvementinflexibilityofjoints,andrangeofmovements.Thishelpsthepatientincarryingoutday‑to‑dayactivitiesindependently,thusreductioninthisscoreindicatesimprovementintheQOLofthepatients.TherewasnosignificantreductioninWOMACscoresbetweenthegroupsduringthefollow‑upperiod.InastudybySmithetal., itwasobserved thatNSAIDssuchaspiroxicamandnaproxenreducedpainsimilartoopioidsinpatientswithOAoftheknee.[17]ReductioninVASandWOMACscorestothesameextentbyboththedrugsinourstudyimpliesthattheyareequallyefficaciousinreducingthesymptomsandsignsofOA.
Wealso assessed thePSSat 2nd, 4th, and6thweek. Inboththegroups,morenumberofpatients expressed satisfactionas “Good” with the study medications. There was animprovementinPSSinboththegroupsfrom2ndweekto4thand6thweek[Figure3].Therewasnosignificantdifferenceinthesatisfactionscorebetweenpiroxicamandnaproxen(P=0.10).This shows thatpatients inboth thegroupshadpain reliefandwere able to perform their regular activitieswith lessdependence.Most of our patientswere in thefifth decadeof life duringwhich they have to depend on their familymembersforsupport,sincetheycouldcarryouttheiractivitiesindependently,theirsatisfactionscoresimproved.
In this study, bothmedicationswerewell‑tolerated, andadverse effectsweremild in nature.The adverse effectssuch as epigastric discomfort, nausea, and vomiting,wereobservedwithboththedrugs,butthenumberwasmorewithnaproxen than piroxicam, and thesemanifestationsweretreatedsymptomatically. In thestudydonebyRichyetal.,patientswithOAof knee observed that piroxicam causedlesser adverse effects compared to otherNSAIDs exceptmeloxicam.TheadverseeffectswerelessevenwithtwicedailyadministrationofpiroxicamcomparedtooncedailyintakeofotherNSAIDs.[14]
conclusIon
The pain relief and patient satisfactionwere similarwithboththedrugsbutanumberofadverseeffectswerelesswithpiroxicam,suggestingittobeabetteralternativetonaproxeninpatientswithOAofkneejoints.
Financial support and sponsorshipNil.
Conflicts of interestTherearenoconflictsofinterest.
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