Rev. bras. ortop. vol.50 número4

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rev bras ortop.2015;50(4):482–485

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Case

Report

Atypical

femoral

fracture

due

to

chronic

use

of

bisphosphonates:

case

report

夽

Eduardo

Frois

Temponi

∗

_,

_Lúcio

_Honório

_de

_Carvalho

_Junior,

_Lincoln

_Paiva

_Costa

HospitalMadreTeresa,BeloHorizonte,MG,Brazil

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Articlehistory: Received13July2014 Accepted26August2014 Availableonline10July2015

Keywords: Osteoporosis Femoralfractures Bisphosphonates

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Thecausalrelationshipbetweenchronicuseofbisphosphonatesandoccurrencesofatypical femoralfractureshasnotyetbeenestablished.Nonetheless,itisknownthattheirchronic useismorerelatedtofractureswithapatterndifferingfromthatofclassicalosteoporotic fractures.Atypicalfracturesarestillrareeventsandthebenefitfromusingbisphosphonates remainsgreaterforpreventionandtreatmentofosteoporosis.Therearefewstudiesguiding thediagnosisandmanagementofthesefractures,thusmakingitdifficulttoachievebetter results.Inthisreport,wepresentthecaseofanelderlypatientwithanatypicalfemoral fracturethatwasmanagedinaccordancewithguidancefromtheAmericanSocietyfor BoneandMineralResearch.

Fratura

femoral

atípica

devida

a

uso

crônico

de

bifosfonato.

Relato

de

caso

Palavras-chave: Osteoporose Fraturasdofêmur Bifosfonato

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Arelaçãocausalentreousocrônicodosbifosfonatoseaocorrênciadefraturasfemorais atípicasnãotemsidoaindaestabelecida.Todavia,sabe-sequeousocrônicodosbifosfonatos temtidomaiorrelaçãocomfraturascompadrãodiferentedasclássicasfraturas osteoporóti-cas.Fraturasatípicassãoaindaeventosraroseobenefíciodousodosbifosfonatosaindaé maiornaprevençãoenotratamentodaosteoporose.Poucosãoosestudosqueorientamo diagnósticoeaconduçãodessasfraturas,oquedificultamelhoresresultados.Nesterelato apresentamoscasodepacientedaterceiraidadecomfraturafemoralatípicaconduzida segundoorientaçãodaSociedadeAmericanaparaPesquisaÓsseaeMineral.

夽

WorkperformedintheOrthopedicsandTraumatologyService,HospitalMadreTeresa,BeloHorizonte,MG,Brazil.

∗ _{Corresponding}_author_.

E-mails:dufrois@hotmail.com(E.F.Temponi),luciohcj@gmail.com(L.H.deCarvalhoJunior). http://dx.doi.org/10.1016/j.rboe.2015.06.016

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rev bras ortop.2015;50(4):482–485

483 Introduction

Bisphosphonatesaretodayamongthemaintypesof medica-tionsprescribedworldwidefortreatingosteoporosis.Several studies have proven that they have an important role in reducing theincidenceofvertebral and non-vertebral frac-tures when used for treating senile and postmenopausal osteoporosis.1,2 _The_indications_for_using_these_medications alsoextendtoothermetabolicdiseasessuchasbone metas-tasis, Paget’s disease and hypercalcemia.3,4 _The _action _of bisphosphonatesoccursthroughinhibitionofthefunctionof osteoclasts.Thisinducesapoptosisofosteoclastsand gives risetosignificantsuppressionofremodelingandconsequent lossofbonebalance.5_However,_the_use_of_these_medications isnotfreefromcomplications.

Severalcaseserieshavealreadyindicatedthatthereisan associationbetweenatypicalfemoralfracturesandprolonged use ofbisphosphonates. These fractures differfrom classi-calosteoporoticfractures inseveralrespects,including the mechanismofaction,locationandfractureconfiguration.6–8 AlthoughtheAmericanSocietyforBoneandMineralResearch (ASBMR)haspublishedguidelinesforevaluatingandfollowing upfracturesthatareconsideredatypical,littleisknownabout thisparticulargroupofinjuries.9_The_aims_of_the_present arti-cleweretopresentacaseofatypical fracturinginducedby chronicuseofbisphosphonatesandtoreviewthe characteris-tics,epidemiology,pathogenesisandtreatmentofsuchcases, soastoaidorthopedicsurgeonsinconductingsimilarcases.

Case

report

Thepatientwasa90-year-olddark-skinnedwomanofweight 75kgandheight1.50m,whopresentedapainfulconditionof mechanicalpatterninherrightthighthatstartedin Novem-ber2013.Previously, shehad been abletowalk withinher community.Shesufferedinvolutionofhergaitpatternasthe painfulconditionintensifiedandbecamecapableofwalking onlyathome,withthehelpofawalkingframe.Shedidnot haveanyhistoryoffallsoranylocaltraumaticfactor.Shewas knowntopresentsystemicarterialhypertension, non-insulin-dependentdiabetesmellitus,cardiopathyandosteoporosis, whichwereallbeingtreatedwithdrugs.

Shesoughttheorthopedicsandtraumatologyoutpatient clinicofourserviceinFebruary2014,inordertohaveher com-plaintinvestigated.Shehadahistoryofaleft-sideproximal femoralfracture6yearspreviously,whichhadbeentreated atourinstitution,withoutanycomplaint.Shealsoreported thatsincethen,shehadbeenusingcalciumreplacementand hadkeptonusingbisphosphonatesoverthesameperiod.She didnotpresentanyabnormalityintheclinicalexamination, exceptfordiscomfortinherrightlower limb,atthighlevel when walking. Serial radiographs demonstrated normality andgoodevolutionoftheleft-sidefracturethathadpreviously beentreated,butwitharchingofthefemoralcorticalboneand sclerosisofthelateralwallinitsmiddlethird.Inthelightof thesefindings,magneticresonanceimagingofthethighwas requested.Thisshowedthepresenceofincomplete fractur-ingoftheposterolateral/lateralcorticalbonewiththickening

oftheadjacentcorticalboneandboneedema,inassociation withslightunilamellarperiostealthickening.Investigationof laboratoryparametersdidnotshowanyassociatedmetabolic abnormality(Fig.1).

Giventhesefactorsandthesymptomaticcondition,a sur-gicalapproachwasindicated.Therewasdiscussionregarding the best fixation method: intramedullary fixation using a cephalomedullarynailorfixationusingaplate.Inthisspecific case,aninitialattemptwasmadetouseanintramedullary nail,butbecauseofdiaphysealarchingandtheriskof wors-eningtheexistingfracture,itwasdecidedtoplacealocked plateasabridge.

Today,thepatientpresents4monthsofpostoperative evo-lution, with involution of the symptomatic condition and improvementofthegaitpattern,andwithoutanycomplaints. Shealreadypresentsradiologicalindicationsoffracture con-solidation(Fig.2).Becauseofthehistoryofapreviousproximal femoral fracture and the atypical fracture induced by bis-phosphonates (high risk of new fractures), it was decided tomaintainthesupplementationofcalciumandvitaminD, withdrawtheuseofbisphosphonatesandstartthepatienton denosumab.

Discussion

Becauseofthelackofcriteriafordefiningatypicalfemoral

fractures, the ASBMR has established major and minor

conditions for diagnosing these fractures.The presenceof the major conditions is fundamental for designating the fracture asatypical anddistinguishing itfrom osteoporotic fractures, while the minor conditions may be associated with atypical fractures but are notfundamental (Table1).9 Atypicalfemoralfractureshavebeencorrelatedwithseveral factors,includingAsianancestry,bilateralfractures, indica-tivesignsandsymptoms,chronicuseofcorticosteroidsand proton pumpinhibitors, vitaminDdeficiencyandpresence ofdiabetesmellitusandrheumatoidarthritis.7,8_The_ASBMR has estimated that the accumulated incidence of atypical fracturesis0.9to78casesper100,000individualsperyear. Theincreaseeachyearistwocasesper100,000after2years

Table1–Majorandminorconditionsfordiagnosing

atypicalfemoralfractures.

Majorconditions Minorconditions

-Absenceofanytraumatic conditions

-Femoralfractureinany diaphyseallocation:frombelow thelessertrochantertoproximal tothesupracondylarregion -Transverseorshortoblique fracture

-Non-comminutivefracture -Medialspokeincomplete fractures;fracturesthatinvolve onlythelateralcorticalbonein incompletecases

-Periostealthickeningin thelateralcorticalbone -Indicativesymptoms -Comorbiditiesin associationwiththeuseof medicationsthat

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rev bras ortop.2015;50(4):482–485

Fig.1–Preoperativeradiologicalevaluation.(a,b)Radiographicimagesshowingareaofsclerosisinthemiddlethirdand synthesismaterialfrompreviousfemoralfractureand(c,d)magneticresonanceimagingslicesshowingareaofincomplete fractureintheposterolateralcorticalbone,withpermeatingedema.

ofuseofbisphosphonatesandthisrisesto78per1,000,000 everyyearafter8yearsofuseofthismedication.9

Severalpathogenicmechanismsthatexplainthe relation-ship betweenchronicuse ofbisphosphonates and atypical femoralfractureshavebeenstudied.Chronicuseis respon-sibleforthedeleteriouseffectonbonequality,becausethis inhibits bone remodeling atcell level. Although increased remodeling predisposes toward bone fragility, this effect

also contributes toward an accumulation of architectural damage, reductionof the heterogeneity ofthe cell matrix, increasedglycationofthefinalproductsandlossesthrough remodeling.1,2,7–9 _After_a_condition_of_atypical_femoral frac-turehasbeendiagnosed,useofbisphosphonatesshouldbe halted.TheideaofvitaminDandcalciumsupplementation should beevaluated; introduction of bone anabolic agents shouldbeconsidered(denosumaborteriparatide);laboratory

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rev bras ortop.2015;50(4):482–485

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testsshouldbeusedtoidentifyanyexistenceofpredisposing metabolicconditions;thecontralateralsideshouldbe eval-uated, given that the risk of bilaterality is 28–44.2%; and lastly,the best fixationmethod should beevaluated.8,9 _No controlledstudiescomparingfixationwithplatesandscrews inrelationtointramedullaryfixationhavebeenconducted, althoughthelatterhasthetheoreticalbenefitofpresenting consolidationthroughendochondralrepair.Therefore,there is a certain degree of preferencefor using nails for treat-ingatypicalfemoralfractures.8–10_Despite_all_the_care_that_is takentoday,andthebetterknowledgeavailable,the progno-sisforthesefractures isstillpoor,withdescriptionsofthe needtorepeat the procedure inup to44% ofthecases in somestudies.Thetimetakenforconsolidationtobeachieved thathasbeendescribed intheliteraturerangesfrom12 to 60months.

The screening for evaluating bone abnormalities in all patients receiving bisphosphonates is inadequate because of the low incidence rate of these fractures and because radiological abnormalities are often unidentifiable. Never-theless, in view of the presence of pain of mechanical patterninpatientswhomakechronicuseofbisphosphonates, carefulassessmentneedstobemadeusingserial radiolog-icalimaging,scintigraphyandmagneticresonanceimaging, in order to institute early diagnosis and treatment.5,8–10 Because many questions relating to atypical femoral frac-turesstilldonothaveanswers,furtherstudiesaimingtoward better histomorphometric and bone biomechanical evalu-ations and the relationship of these fractures to certain medications are fundamental.Moreover,discussiontoward creating a national register of atypical femoral fractures will ensure better understanding and discussion of these cases.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgment

TheauthorsacknowledgetheFroisTemponifamilyformaking thedataandimagesofthecaseavailable.

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