Rev. Bras. Reumatol. vol.55 número1

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

ww w . r e u m a t o l o g i a . c o m . b r

Brief

communication

Analysis

of

the

influence

of

pharmacotherapy

on

the

quality

of

life

of

seniors

with

osteoarthritis

Katia

F.

Salvato

_,

_João

_Paulo

_M.

_Santos

_,

_Deise

_A.A.

_{Pires-Oliveira}

_,

_Viviane

_S.P.

_Costa

_,

Mario

Molari

_,

_Marcos

_T.P.

_Fernandes

_,

_Regina

_C.

_{Poli-Frederico}

_,

Karen

B.P.

Fernandes

a_{UniversidadeNortedoParaná,Londrina,PR,Brazil}

b_{PontifíciaUniversidadeCatólicadoParaná,Londrina,PR,Brazil}

a

r

t

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e

i

n

f

o

Keywords:

Osteoarthritis Elderly

Functionalstatus Functionaldisability Qualityoflife

a

b

s

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t

Aims: Thisstudyaimedtoassesstheinfluenceofpharmacotherapyonhealth-related qual-ityoflifeofelderlywithostheoarthritis.

Methods:Longitudinalstudyinvolving91olderadultsfrombothgenders(Age:70.36±5.57 years) from EELO project with self-reported knee or hip ostheoartritis, confirmed by radiographicanalysis.Dataregardingpharmacotherapywasassessedbyastructured ques-tionnaireandthequalityoflifewasanalyzedbySF-36questionnaireattheinitialmoment andtwoyearsthereafter.Alldomainsfromqualityoflifeweregroupedinphysicaland mentalcomponentsforfurtherdataanalysis.

Results:Astatisticallysignificantdeclineinbothphysicalandmentalcomponentsofquality oflifewasobserved(Wilcoxontest,p<0.05).However,itwasobservedaslighteddeclinein physicalcomponentsingrouptreatedwithchondroitin/glucosaminewhencomparedto other groups,accordingtoKruskal–Wallistest(p=0.007).Ontheotherhand,itwasnot observedanyinfluenceofpharmacologicaltreatmentonmentalcomponentsof health-relatedqualityoflife(p>0.05).

Conclusions: Treatmentwithcondroitin/glucosamincontributestoalowerdeclinein physi-calcomponentwhileithadnoinfluenceonmentalcomponentofhealth-relatedqualityof lifeinolderadultswithostheoartritis.

©2014ElsevierEditoraLtda.Allrightsreserved.

∗ _{Correspondingauthor.}

E-mail:[email protected](K.B.P.Fernandes). http://dx.doi.org/10.1016/j.rbre.2014.08.005

Análise

da

influência

da

farmacoterapia

sobre

a

qualidade

de

vida

em

idosos

com

osteoartrite

Palavras-chave:

Osteoartrite Idoso

Funcionalidade Incapacidadefuncional Qualidadedevida

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e

s

u

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o

Objetivos: Analisarainfluênciadafarmacoterapiadaosteoartritenaqualidadedevidade idosos.

Métodos: Estudolongitudinal,doqualparticiparam91idososdeambososgêneros(idade: 70,36±5,57 anos), integrantes do projeto Estudo sobre Envelhecimentoe Longevidade (EELO),portadoresdeosteoartritedequadrile/oujoelho,confirmadaporanálise radiográ-fica.Foramlevantadosdadossobreafarmacoterapiadaosteoartritemedianteousode questionáriosestruturadoseaqualidadedevidafoianalisadapeloquestionárioSF-36,no momentoinicialedoisanosapósacoletadedados.Osdiferentesdomíniosdaqualidade devidaforamagrupadosemdomíniosfísicosementaisparaposterioranálisedosdados.

Resultados:Foiobservadoumdeclínioestatisticamentesignificativotantonoscomponentes físicosquantomentaisdaqualidadedevidadosindivíduos(testedeWilcoxon,p<0,05).Foi observadomenordeclínionocomponentefísicodaqualidadedevidaparaosusuáriosde condroitina/glicosaminaemcomparac¸ãocomogrupotratadocomanti-inflamatóriosou nãotratado,segundootestedeKruskal–Wallis(p=0,007).Poroutrolado,nãofoiobservada influênciadotratamentofarmacológicosobreocomponentementaldaqualidadedevida (p>0,05).

Conclusão: Otratamentocomcondroitina/glicosaminacontribuiuparamenordeclíniodo componentefísico enãoinfluenciou oscomponentesmentaisda qualidadedevida de idososcomosteoartrite.

©2014ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Osteoarthritis(OA),alsoknownasarthrosisand

osteoarthro-sis, is a chronic degenerative disease caused by the

deteriorationofthecartilageandtheformationofmarginal osteophyte,withboneoutgrowthsonthesurfacesandatthe marginsofthejoints.1 _{Itischaracterizedbypainand} func-tional limitations,it has slow evolution, as aresult ofthe imbalancebetweentheformationandeliminationofthemain elementsofthecartilage.2

OA is age-related,1 _{being the rheumatic disorder more} prevalentamongtheelderly,3_{affectingapproximately10%of} theworld’selderlypopulation.4_{Despitethereisnoaccurate} datainBrazil,Backerstudy5_{showsprevalenceof26.3%.Inthis} context,itrepresentsoneofthemostfrequentcausesof dis-abilityandpaininthemusculoskeletalsystem.3_KneeOAis themostcommonmanifestation,affecting23%oftheelderly population,althoughthesenumbersareevenhigheramong elderlywomen.6_{However,theprevalenceofOAcanreach40%} amongindividualsaged74orolder.6

Thecartilagelesionmaybecausedbyamechanical aggres-sionorduetoinflammatoryjointdisease,andithasstrong geneticpredisposition.1,2

Its pathophysiology is characterized by severe changes in the joint surface (loss of articular cartilage, ulceration, remodelingandsclerosisofthesubchondralbone),with sud-denbiochemical changesinthe proteoglycans,resulting in catabolicandanabolicprocessesinthecartilagemetabolism, withreducedlevelsofchondroitinandglucosaminesulfates.1

Its symptoms are basically constant: localized articular

pain, which accentuates with increasing load and

move-ment(worseatthebeginningofthemovementandatrest), reduced range of motion, muscle weakness,joint stiffness afterrest,crepitusandincreasedarticularvolume,with conse-quentprogressiveinabilitytoperformusualactivities,suchas gait.1

OAisinitiallytreatedwithphysicalmeasures,analgesics, steroidalandnonsteroidalanti-inflammatories(NSAIDs),and surgical treatment is indicated for the most severe cases only.However,basedontheactualknowledgeofthedisease

pathophysiology, disease modifying drugs, such as

chon-droitin and glucosamine seems to be able to abolish or

reduce its symptoms, increasing functional status of the patients.2,7

Qualityoflifeisanimportantitem inthehealthofthe individual that should be considered in the study of OA.8 AccordingtotheWorld HealthOrganization(WHO),quality oflifeistheindividual’sperceptionoftheirpositioninlife, inthecontextofcultureandinthevaluesystemsinwhich they live and inrelation totheir goals, their expectations, theirstandardsandconcerns.9_{Theinstrumentsthatassess} qualityoflifemaybeinfluencedbytheimpactofthehealth conditioninlife,includingthephysical,emotionalandsocial domains.10

Patients

and

methods

Ethicalprocedures

ThisstudywasapprovedbytheResearchEthicsCommittee (protocolno.0063/09).Beforeanyprocedurewasundertaken, patientswere briefedonthenatureoftheworkandsigned afreeandinformed consentforminwhichtheyagreed to participateinthestudy.

Outlineandstudypopulation

Ninety-oneelderlypatientswithOAfromasubsampleofEELO projectwereincludedinthislongitudinal,observationalstudy.

EELO was a thematic project developed in the city of

Londrina, Paraná, which aimedto examine the social and

demographicconditionsandhealthindicatorsofelderly indi-viduals of this city.The project had a totalsample of508 seniors,whowereselectedinarandomandstratifiedmanner fromtherecordsofBasicHealthUnitsfromthiscity.

Thecriteriaforinclusionwere patientsofbothgenders, aged60yearsorolderanddiagnosisofhipandkneeOA,either receivingclinicallyprescribeddrugtreatmentornotandwho hadsignedafreeandinformedconsent.

The criteria for exclusion were individuals with full or partialprostheticsinanyofthejointsbeingevaluated,with concomitant diagnosis of other osteoarticular/muscle dis-eases, suchas rheumatoid arthritis,fibromyalgia, systemic

lupus erythematosus and other rheumatic diseases with

severecognitive impairmentorthose whohavenotagreed tosignthefreeandinformedconsentform.

Instrumentation

Astructuredinterviewguidewithquestionsaboutgender,age, weight,height, race,previous occupation and occupational statuswasusedtocharacterizetheprofileofseniorpatients withOA.Theformula:weight(kg)/height2 _(m2_)wasusedto

calculatethebodymassindex(BMI).

Astructuredquestionnairewithinformationaboutdrug type,dosageanddurationofthetreatmentofpatientswithOA wasusedtoevaluatethedrugtreatmentadoptedbythe indi-viduals.Thenthepatientsweredividedintothreesubgroups accordingtothetreatment,forfurtherstatisticalcomparison: controlgroup(individualswhoarenotmakinguseof med-ication forOA), anti-inflammatorygroup (individualsbeing treated with steroidal anti-inflammatories and NSAIDs) or thechondroitin/glucosaminegroup(individualsbeingtreated withthechondroitin+glucosamineassociation).

The Medical Outcomes Study 36 Short-Form Health

Survey(SF-36) questionnaire, translated and validated into PortugueseandcurrentlyrecommendedbytheAmerican Col-legeofRheumatology,wasusedtoassessthequalityoflife. TheSF-36questionnaireisaninstrumentthatcoversthe fol-lowingdomains:functionalcapacity,physicalaspects,bodily pain,generalhealthcondition,vitality,socialaspects, emo-tionalaspectsandmentalhealth.

The first four domains (functional capacity, physical aspects, bodily pain, general health condition) assess the

physicalhealth orphysicalcomponent, whilethe last four (vitality,socialaspects,emotionalaspectsandmentalhealth), thementalhealthormentalcomponent.Thescoreofeach domainvariesfromzeroto100,inwhichzerocorrespondsto theworsthealthconditionand100,tothebest.Eachdomain isanalyzedseparately,andthereisnooverallscore.11

Procedures

Data collection procedures were carriedout intwo stages. Withtheobjectiveofevaluatingthevariationinthequality oflifeoftheseelderlypatientsovertimeandwith pharma-cotherapy,thesewerereevaluatedtwoyearsaftertheinitial collection,i.e.,thefirstevaluationwasmadein2010andthe secondin2012.

Statisticalanalysis

AdatabasewaspreparedintheStatisticalPackageforSocial Sciences(SPSS)program,version15.0,fromthedatacollected. Aconfidenceinterval(CI)of95%wasestablishedforalltests applied(p<0.05).

Initially, the Shapiro–Wilk normality testwas usedand, as the datadid notdisplaya normaldistribution, descrip-tivedata,suchasmedianand interquartilerange(median; Q1–Q3)andnonparametrictestswereappliedtocomparethe groups.

TheWilcoxontestwasusedtocomparethedifferencein the physical and mentalcomponents ofthe life qualityof eachgroupbetweenevaluations(initialevaluationandfinal evaluation,carriedouttwoyearsaftertheinitialanalysis).

Inordertoanalyzeifanypharmacologicaltreatmentwould be related to a smaller decline of functional capacity, the variationofphysicalandmentalcomponentsofthequality oflife () wascalculated, and the Kruskal–Wallistest was usedtocomparegroupsunderdrugtreatment(control× anti-inflammatory×chondroitin/glucosamine).

Results

Ninety-oneelderlypatientswithOA,predominantly female (71.4% of the sample), participated in the study. The age oftheindividualswas 70.4±5.6years,and itwasobserved thatthestudypopulationpresentedhighBMI(29±5.2).The descriptive data of the study population are presented in Table 1. Table 2 lists the results ofthe groups inthe first andsecondevaluations,withastatisticallysignificantdecline of the physical and mental components of quality of life (p<0.05, Table 2) in all groups, according to the Wilcoxon test.Itwasobservedthatusers ofchondroitin/glucosamine hadasmallerdeclineinthephysicalcomponentofquality oflifewhencomparedtothegroupbeingtreatedwith anti-inflammatories,oruntreated,accordingtotheKruskal–Wallis test(p=0.007,Table2,Fig.1A).Ontheotherhand,theinfluence

of the pharmacological treatment on the mental

–100 –50 0 50

–100 –50 0 50

Control

Anti-inflammatory

Chondroitin/Glucosamine

Control

Anti-inflammatory

Chondroitin/Glucosamine

Physical Comp.

∇

Mental Comp.

∇

A

B

Fig.1–Variationofphysical(PhysicalComp.,A)andmental(MentalComp.,B)componentsofqualityoflifeinrelation topharmacologicaltreatment.

Table1–Characterizationofthevariablesofthestudy population.

Variables Average Standard

Deviation

Age 70.36 5.57

BMI 28.99 5.25

Gender Absolute

frequency(n)

Relative frequency(%)

Male 26 28.6

Female 65 71.4

Total 91 100.0

Pharmacologicaltreatment Absolute frequency(n)

Relative frequency(%)

Control 50 54.9

Anti-inflammatorydrugs 27 29.7

Chondroitin/Glucosamine 14 15.4

BMI,bodymassindex.

Discussion

OAisthemostcommonjointdiseaseintheworld,6_which jus-tifiestheimportanceofthestudyofthisdisorderonqualityof lifeofseniorpatients.Moreover,OAiscloselyrelatedtoaging, causingpainandfunctionaldisability,withmajorsocial, psy-chologicalandeconomiclosses,triggeringtheworseningof qualityoflifeoftheseindividuals.5

Astheindividualages,thediseasetendstoprogressasa resultofthebiomechanicalaspects,causingdeficitin func-tionalityandqualityoflife,10_{sincethereisaprocessinversely} proportionalbetweendiseaseprogressionandthequalityof lifeofpatients,12_{asdemonstratedintheresultsofthisstudy.} TheBMIaveragewas28.99,corroboratingotherstudiesthat showanassociationbetweenOAandoverweight,since obe-sityisthemostsignificantfactorfortheonsetofthedisease.13 In addition to that, obesity isassociated withlower social classes.14

Thissamplewascomposedmostlybywomenand, accord-ingtoevidenceobservedinotherstudies,womentendtohave greaterjointinvolvementasthequalityoflifedeclines,10 facil-itating the explanation ofthe negative variation perceived inallgroups.Thisresultcouldbeexplainedbygreaterjoint

Table2–Comparisonofgroupsinofthe1stand2ndevaluationsandwithregardtovariationofphysicalandmental componentsofqualityoflife.

Groups Lifequality

1stevaluation

Lifequality2nd evaluation

p

Physicalcomponents

Control 77.500 48.375 <0.001

Anti-inflammatorydrugs 78.667 48.000 <0.001

Chondroitin/glucosamine 80.417 56.375 0.003

Mentalcomponents

Control 87.625 65.437 <0.001

Anti-inflammatorydrugs 82.275 55.662 0.037

involvement,probablyassociatedtoclinical and functional

changes.15_{OAismuchmorefrequentamongwomenabove}

theageof55,16_{especiallyamongwomenfromlower social} classes.14

Thus,onecaninferthat poorer qualityoflifeis associ-atedwithaworsefunctionalcapacityofpatientswithOA,17 sincethemainproblemsofOAarepainanddiscomfort,which inturn cause functional limitations and changes in social behavior.18

Whileseveraladvanceshavebeenmadeintryingto elu-cidatethepathogenesisoftheOA,focusingonjointdamage andchangesinthejoint’ssynovialfluid,19_{thereisstillnocure} forthisdisease,12_{anotherfactorthathelpsusunderstanding} theworseningofthequalityoflifeofthepatientsobservedin thisstudy.12

Althoughthereisnocure,treatmentscanbedividedinto conventional(drugandphysiotherapy)andsurgical,andthe choiceoftreatmentwilldependlargelyontheseverityofthe jointdamage.12

Thepharmacologicaltreatmentaimstorelievethesigns and symptomsof the disease and wheneverit is possible, reduceitsprogression.Thus,thegoalsofthistreatmentare painrelief,improvingthequalityoflife,increasingmobility, increasingtheabilitytowalkandreducingtheprogressionof thedisease.12

It was observed that the group treated with the chon-droitin/glucosamine association showed a statistically less significantvariation,leadingtotheassumptionthatthisclass wouldhavebetterclinicalefficacy.Theglucosaminesulfate associated with chondroitin hydrochloride belongs to the groupofOA-modifyingdrugs.Itisknownthatthedrugblocks apotentialchangeoftheviscoelasticpropertiesofthe carti-laginoustissue.12

The variation observed in the group treated with anti-inflammatorydrugs didnot showa statisticallysignificant difference,probablyduetomodeofactionofthisdrugtype thatactonthegeneraltreatmentofsymptoms(pain,feverand inflammation).However,thereisstillcontroversyovertheir effectivenessinpainfrommusculoskeletalconditions,with significantvariationintheresponseofthesedrugsaccording toeachindividual.20_{Accordingtoseveralrandomclinical} tri-als,NSAIDsproducedbetterresultswithregardtopainwhen comparedtoplacebo,butwithworseresultswhencompared topatientstreatedwithpainkillers.21

NSAIDs operate by inhibiting the synthesis of

prostaglandins, which is known as a primary

anti-inflammatorymechanism;prostaglandinsare inflammatory

mediators that contribute to pain and inflammation in a

process mediated by cyclooxygenase enzymes (COX-1 and

COX-2),19 _{i.e., they inhibit COX-1 and COX-2. Despite the} biomechanicalcharacteristicsofthedisease,its

pathophysi-ologyis causedbyanimbalancebetween themechanisms

offormationanddegenerationofthecartilagematrix,being this process regulated byproinflammatory cytokines, such asthe interleukin-1(IL-1), the tumornecrosisfactor alpha (TNF-alpha)andproteinases.Despitebeingwidelyused,the efficiencyandsafetyofNSAIDsasamethodoftreatmentof OAhavenotyetbeenelucidated.12_{Thesizeofthesampleand} thelackofevaluationofdrugseffectsinthesenseofbeingor notbeingdose-dependentwerelimitingfactorsforthisstudy.

Therefore,wesuggestsubsequentpopulation-basedstudies toconfirmtheseresults.

Conflicts

of

interest

Theauthorsdeclarenoconflictofinterest.

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