1

etal-on-metalbearingsintotalhipreplacementhaveexperiencedaresurgenceofpopularityinrecenttimes.Thisisduemainlytoasignificantnumberoflong-termclinicalstudieshighlightingtheremarkablylowwearratesofmetal-on-metalbearingsimplantedoverthepast40years.1-4Clinicalcomplicationswiththeearlygenerationcomponentsusuallywererelatedtomanufacturingissuessuchas,impropertolerancesandpoordesign.5Recentadvancementsinmanufacturingtechnologyhaveenabledmoreprecisetolerances,surfacefinish,anddesignsthatprovideanincreasedrangeofmotion(Figure1).DocumentedclinicalsuccesswithmoderndeviceshasledtotheFDAgrantingmarketapprovaltosomeorthopediccompaniesintheUS.6,7

etal-on-metalbearingsintotalhipreplacement

Introduction

M

MetalIons–AScientificReview

Metal-on-metalisparticularlyattractiveinthetotalhipnotonlyduetotheultra-lowwearexhibitedinnumerousclinicalandsimulatorstudies1–8(Figure2),butalsoduetotheflexibilityaffordedbydesignsbasedonthepropertiesofcobaltchromiumalloy.Thisflexibilityenablestheuseoflargediameterheadsinavarietyofacetabularconfigurations.Largermetal-on-metalfemoralheadscanprovideincreasedrange-of-motionandstability,aswellasincreasedresistancetodislocation.9-12Theincorporationoflargerdiameterfemoralheadsintoceramicandpolyethylenebearingspresentsdesignchallengesduetoimpingementconcernswithceramics,andincreasedbrittlenesswiththinpolyethyleneliners,allleadingtoanincreasedriskofmechanicalfracture.13,14Metal-on-metalcomponentsdonotposeariskofmechanicalfracture.Currentmetal-on-metaldesignsallowtheuseofthelarger38mmheadsinacetabularcomponentsizesassmallas46mm.

Despiteitslengthyandpositiveclinicalhistory,therehavebeenconcernsexpressedregardingthelong-termbiologicalconsequencesofmetal-on-metalweardebris,particularlythereleaseofcobaltandchromiumionsintothebody.Questionsaboutmetalionsandtheirbiologicaleffectsarenotnew.Manystudieshavebeenconductedoverpastdecades.Allhavefailedtoestablishacausallinkbetweenionrelease,andcancerorothernegativesystemiceffects.15–22Aswitheachbearingsurface,certainunknownsstillexist,andinrecenttimes,fueledbyrumorsandmisinformationaboutthemetalions,thedebatelingerson.Followingarefivereasonswhymanyleadingresearchersconsiderthemetaliondebatetobeinconsequential.

Metal-on-metalhasexhibitedultra-lowwearratesnotonlyinsimulatorstudies,butalsothroughpublishedin-vivowearstudiesasshowninthein-vivowearcomparisonabove.

RadialClearanceµmSphericity=10µmSurfaceFinishRa=1µm

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Figure1

Figure2

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itallium™orcobaltchromiumalloyhasbeeninuseinorthopedicsformorethan80yearssinceitsfirstusebyDr.Smith-Petersenintotalhipreplacementsurgeryin1917.23Thestrengthanddurabilityofcobaltchromehasbeenappliedtoavarietyofbearingsurfacesovertheyearsincludingtotalknees,elbows,shouldersandhips.Cobaltchromewasfirstusedinmetal-on-metalapplicationsasearlyas1958indesignssuchastheRing,Muller,McKee/Farrar,andSivashprostheses.Sincethoseearlydaysoforthopedics,hundredsofthousandsofpatientshavereceivedmetal-on-metalimplants,withthemajoritybeingimplantedinEurope.Interestingly,40yearsandhundredsofthousandsofimplantslater,metal-on-metalionreleaseremainsanon-issueamongmostEuropeanorthopedicsurgeons.

Throughoutthehistoryofmetal-on-metalvariousauthorshaveexaminedtheionreleaseissue.Followingarebriefsummariesofsomeoftheirfindings.

TheRiskofCancerFollowingTotalHiporKneeArthroplasty,JBJS,May200115

Dr.Tharani,etal.,reportedontheriskofcancerfollowingtotalhiporkneearthroplasty.15Ninedifferentstudiesencompassing140,000totalhipandkneecaseswerecombinedandstatisticallyevaluatedinordertocomparetherelativeriskofcancertothatofthegeneralpopulationoracontrolgroup.Intheseninestudiesatotalof25casesofmalignantdiseasewerereported,and34%ofthecancersoccurredwithinthefirsttwoyearsofimplantation.Thesefindingsshowed,“theavailabledatadonotsupportacausallinkbetweentotalhiparthroplastyandthedevelopmentofcancer.”Inaddition,noincreasedriskofcancerwithametal-on-metalhipimplantversusapolyethyleneimplantwasfound.Long-termconcernsaboutmetal-on-metalinthehipshouldbeweighedagainstthestudydatashowingthat34%ofthecancersaftertotaljointreplacementoccurredwithinthefirsttwoyears,andwerenotassociatedwiththetotaljointimplant.

1 Cobaltchromealloyisaknownmaterial.

V Cobaltchromehasbeenusedinawidevarietyoforthopedicimplantsoverthepast80yearsincludingthishipimplantfromtheearly20thcentury.

Cobaltchromewasfirstusedinmetal-on-metalapplicationsasearlyas1958indesignssuchastheMuller,McKee/Farrar,SivashandRing(picturedontheleft)prostheses.

2 3

CancerRiskAfterMetal-on-MetalandPolyethylene-on-MetalTHA,CORR,August199616Dr.Visuri,etal.,alsostudiedthecancerriskaftermetal-on-metalandpolyethylene-on-metaltotalhiparthroplasty.16Thestudyinvolved579metal-on-metalpatientsand1,585metal-on-polyethylenepatientswithupto16yearfollow-up.Theirobjectivewastocomparetheincidenceofcancerafterbothmetal-on-metalandmetal-on-polyethylenetotalhipreplacementtothatofthegeneralpopulationinFinland.Therewasnostatisticallysignificantincreaseincancerofanytype,at16-yearfollow-up,witheitherametal-on-metalormetal-on-polyethylenecomparedtotheexpectedcancerrateofthegeneralpopulation.Theauthorsconcludedthat,“theobservedvariationintheincidenceofdifferentcancersamongpatientswhohadtotalhiparthroplastycomparedwiththegeneralpopulationsuggeststhatfactorsotherthantotalhiparthroplastyplayamajorroleintheoriginorcancer”(Figure3).

MOM

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Dr.Visurireportednostatisticallysignificantincreaseincancerofanytypewitheitherametal-on-metalormetal-on-polyethylenehipreplacementcomparedtotheexpectedcancerrateofthegeneralpopulationata16-yearfollow-up.

DistributionofCobaltChromiumWearandCorrosionProductsandBiologicReactions,CORR,August199617Dr.Merritt,etal.,examinedthedistributionofcobaltchromiumwearandcorrosionproductsandthesubsequentbiologicreactions.17Theissueofcobaltchromiumwearandcorrosionproductswasevaluatedinanefforttoseehowthismightrelatetothebiologicperformanceofimplantdevices.Thefindingswereextremelyfavorableasrelatedtoawellfunctioningmetal-on-metalhipimplant.Theauthorsconclude,“itisclearatthisstageintotaljointreplacement,thatmorereportedadversebiologicresponsesareoccurringtothepolyethylenethantothemetal.Itistemptingtoaddressthisissuebyeliminatingthepolyethylene.”

Figure3

4 5

2 Metalionreleaseisnotuniquetometal-on-metaldevices.

etalionsareabyproductofvirtuallyeverymetallicimplant.Nails,screws,stems,metalcups,plates,modularheads,cages,andcableswilleachreleaseionsoftheirperspectivemetals.ThisisfurtherevidencedinstudiesbyDr.Kriebichwhodemonstratedthatloosecobaltchromestemsexhibitequivalentbloodionlevelscomparedtothatofametal-on-metalimplant24(Figure4).

Someceramic-on-ceramicdesignsmayalsoreleasemetalionsreleaseduetometal-on-metalneckimpingementandfrettingatmodulartaperjunctions.

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Cobalt

Chromium

Serumstudiesofmetalionsdemonstratesimilarvaluesbetweenloosecobaltchromestemsandthatofametal-on-metalimplant.

Someceramic-on-ceramicdesignsmayalsoreleasemetalionsduetoneckimpingementandfrettingatmodulartaperjunctions.33Therehavebeencasereportsoffemoralnecknotchingwithsomerecentceramic-on-ceramicdesignsleadingtoexcessivemetaldebris,resultinginmetallosis.25Clearly,invivotransfersofmetalionsarenotuniquetometal-on-metalbearings,sothequestionbecomes:ifwecan’tavoidmetalionsintotalhiparthroplasty,whatisanacceptableamount?Researchershavebeentryingtodefinemaximumvaluesforcobaltandchromiumionsforyears.Themainissuetheyareconfrontedwithisthefactthatyearsofmetalionresearchhaveyettorevealanytoxicsignificanceassociatedwithmetalionsreleasedfrommetal-on-metal

articulations.15-22Therefore,settingamaximumvaluehasnotbeenpossible.Dataontheeffectsofcobaltandchromiuminthebodyatlevelsmuchhigherthanthatofametal-on-metalimplantcanbefoundinstudiesperformedoutsideofthefieldoforthopedics,suchasinthemetalindustry.Forgeneralpurposes,comparisonscanbemadetothemetalionlevelsreportedfrommetal-on-metalimplantstudies.

MMicrogram

sperLiter

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Figure4

4 5

orkersinthemetalindustryaretypicallyexposedtohigherthannormallevelsofthemetalstheyareprocessing.Testshaveshownhigherthannormalbloodionvaluesinfactoryworkersexposedtochromiumandcobalt.

Thesemetalscanbeintroducedintotheirsystemthroughdermalexposure,inhalationandaccidentalingestion.27-31Itshouldbenotedthateventhoughtheseworkersdemonstratebloodionvalues15-20timeshigherthanthatofametal-on-metalimplant,nosystemictoxicityhasbeenestablished.Metal-on-metalionlevelsofchromiumcanalsobecomparedto“studiesonworkercohortswhohavehistoricallybeenexposedwellabovethecurrentpermissiblestandards(IARC,1990),andhavenotshownaconsistentpatternofelevatedcancerincidence”(Figure5)(Proctor,2002).27

3 Casereportsandstudiesofcobaltandchromiuminotherindustriessupporttheuseofmetal-on-metalbearingsinorthopedics.

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Forexample,discussionsoftoxicityhavealsoextendedtothefemalepopulationandpregancy.Inthe1960scobaltwassometimesusedasaremedyforanemiainpregnantwomen.Barcelouxreportedononegroupofwomenreceivingover100,000Mcgofcobaltperday,allofwhomdeliveredhealthyfull-terminfants,andexperiencednoadversesideeffectsrelatedtothecobaltmedication30(Figure8).

W

Metal-on-metalionlevelsofchromiumcanalsobecomparedto“studiesonworkercohortswhohavehistoricallybeenexposedwellabovethecurrentpermissiblestandards,andhavenotshownaconsistentpatternofelevatedcancerincidence.”27

Figure5

6 7

Dr.BrodnerfromVienna,Austriarecentlyreported(Montreal,June2003)onthreepregnantwomenwhowererecipientsofmetal-on-metalhips.Metaliontestingwasperformedatthetimeofdelivery.Traceamountofionscouldbedetectedinthemothers,withnodetectableamountintheumbilicalcords.Dr.Brodnerconcludedthatmetal-on-metalwassafeforwomenofchildbearingageas“theplacentaactsasaneffectivebarrierforcobaltandchromiumdisseminatedfrommetal-on-metalarticulations.”31Notonlyhascobaltbeenusedasamedicineforrefractoryanemia,butchromiumalsohasbeneficialeffectsinthebody,suchasassistinginpropermetabolicfunction.

Adebateaboutmetalionrelease,similartothatoccurringinorthopedics,iscurrentlybeingwagedinthefoodindustry.Someinvestigatorshaveexpressedconcernregardingtheleachingofmetals,suchaschromium,intofoodfrommetalliccookingutensils.Asintheorthopedicfield,somehaveremainedcautious,statingthatmoreresearchinthisareaisneeded.Dr.Aitio,ChiefPhysicianfortheDepartmentofIndustrialHygieneandToxicologyattheFinnishInstituteofOccupationalHealth,concludedthat:“Notoxicityistobeexpectedfromthechromiumleachedfromkitchenware,itmayinfactbebeneficialtohealth,sincetheamountsofchromiuminpresentWestern-typedietsaregenerallysmallincomparisontoamountsconsideredtobeoptimal.”26

Metal-on-Metalhasbeenusedinwomenofchildbearingage.

Debateaboutmetallicionreleasefromfoodutensils.

6 7

ttimesinthemidstofthedebatesregardingmetalions,itishelpfultorememberthatmetal-on-metaldevicesareFDAregulatedandclearedfororthopedicapplicationsbytheUSgovernment.Thegovernmenthasalsoestablishedarecommendeddailyallowanceforchromium.“ChromiumIII(trivalentchromium)isanessentialmicronutrientwitharecommendeddailyrequirementforhumansintherangeof50to200microgramsperday(µg/d).”27Asdemonstratedinthechartbelow,ametal-on-metalhipisassociatedwithbloodchromiumlevelsof3–5Mcg/l,themajorityofwhichisexcretedthoughtheurine.18

Aswithmanyelements,chromiumcanexistinseveralatomicvalencestates.ChromiumVI(hexavalent)andChromiumIII(trivalent)arethetwomostcommon.“ChromiumIIIdisplaysextremelylowornotoxicityviaallroutesofhumanexposureanddoesnotposeacarcinogenichazard(ATSDR,2000;U.S.EPA,1998a;IARC,1990;WHO,1988).”27ChromiumpicolinateisoneformofchromiumIIIthatwassoldinlargequantitiesduringthe“chromiumcraze”ofthemid1990s.Itwaspromotedasawaytoburnfatandregulatemetabolism,andisstillastandardingredientinmanyhealthfoodsupplementsbeingsoldtoday.34,35

“ChromiumVI(hexavalentchromium)isimportanttoavarietyofindustriesincludingpigmentmanufacturingandpainting,metalplating,woodtreating,andleathertanning…”27Hexavalentchromiumcanhaveatoxiceffectinphysiologicalenvironmentsespeciallyifintroducedtothebodyinlargeamounts.

CobaltandChromiummaybebeneficialtothebodyasestablishedbyresearchandlistedbytheUSgovernment.

4

Aswithmanyelementschromiumcanexistinseveralatomicvalencestates.

Chromiumisastandardingredientinmanyhealthsupplementsbeingsoldtoday.

A

8 9

Itiswidelyacceptedthatthevalencestateofchromiumreleasedfromametal-on-metalimplantisprimarilytrivalentwhichisthemorebiocompatibleformofchromium.Also,evenifchromiumionswerereleasedinthehexavalentstate,thelevelsappeartomuchlowerthantheamountsthatmightcausetoxicity,asillustratedinthefindingslistedbelow:

• “recentkineticsandinvivogenotoxicitydatademonstratethatCr(VI)isreducedtonontoxicCr(III)insaliva,intheacidicconditionsofthestomach,andintheblood.”27

• “AtconcentrationsatleastashighasthecurrentU.S.maximumcontaminantlevelof100microgramsperliter(µg/L),andprobablyatleastanorderofmagnitudehigher,Cr(VI)isreducedtoCr(III)priorto,oruponsystemicabsorption.”27

• “Redbloodcelllysateshaveasubstantialandregenerativecapacitytoreduce>100McgofCr(VI)(toCr(III)basedonthehematocritofanaverageadult(DeFloraandWetterhahn,1989;DeFlora,1996).”29

• “EssentiallyalltissuespossessasimilarhighcapacitytoreduceCr(VI)toCr(III),especiallytheliver,whichisresponsibleforthe“firstpasseffect”biotransformationsofmanychemicals(SipesandGandolfi,1991).”29

Currentmetal-on-metalionreleasestudieshaveshowntrivalentchromiumlevelsinserumtobemuchlowerthaneventhe100µg/lmaximumlistedforhexavalentchromium.18–22Also,mostresearchersagreethatchromiumionsreleasedintothebodyfrommetal-on-metalimplantsareinthetrivalentCr(III)state,andaccordingtothestatementsabove,evenifalloftheionsoccurredinthehexavalentCr(VI)state–theycouldstillbereducedtothetrivalentstatewithouttoxiceffects(Figure6).

Currentmetal-on-metalionreleasestudiesshowtrivalentchromiumlevelsintheserumtobemuchlowerthanthe100µg/dmaximumlistedforhexavalentchromium.18,21,27EvenifalloftheionsoccurredinthehexavalentCr(VI)state–theycouldstillbereducedtothetrivalentstatewithouttoxiceffects.

Trivalentchromiumisakeyelementofglucoseregulationandmetabolicfunction.Ithasbeenwidelyconsumedinpillformasameansofhelpingtoregulatediabetes,controlsugarcravings,andaidinweightloss.Ithasbeenthesubjectofmorethan35clinicalstudiesinvolvingover2,000participants36.Therecommendeddailydoseasrecommendedbythesestudiesisaround200Mcgperday(Figure7).ArecentstudyfundedbytheNationalInstitutesofHealthshowedthat:

“Dailysupplementationwith1,000Mcgofchromiumaschromiumpicolinatesignificantlyenhancedinsulinsensitivity.Theseinitialresultsofferapotentialnewnutritionaltherapyforapproximately2millionAmericanwomensufferingfromPolycysticOvarianSyndrome(PCOS).

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ThemaximumamountofCRVIthebodyisabletosafelyconverttoCRIII.27

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Figure6

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PCOSisalittle-understoodhormonalconditionthatisaleadingcauseofinfertility,andisassociatedwithinsulinresistance,gestationaldiabetesandtype2diabetes.”36(Figure7)

obaltalsohasaroleinthebody.CobaltisanessentialelementnecessaryfortheformationofvitaminB12,andthemetabolismofproteins.Consequently,consumingextraproteinandvitaminB12(ie:meatandmultivitamins),maysubstantiallyinfluencetheurinaryconcentrationsofcobalt.Theaveragepersonconsumesbetween5and45micrograms(mcg)ofcobaltperday.30Theamountofcobaltexcretedintheurinefromametal-on-metalimplantappearstobebetween3and350Mcgperday.19-21Inthe1960ssomeheavybeerdrinkersdevelopedcardiacproblemsacoupleofmonthsaftercobaltchloridewasaddedtotheirlocalbeersupply.Theestimateddailyintakeofcobaltbythesebeerdrinkerswas6000to8000Mcgperday.Reducedproteinintakeandapoordietwerealsocitedascontributingtothebeerdrinker’sheartconditions30(Figure8).Assumingacumulativeeffectofcobaltionreleasefromametal-on-metalimplant(inotherwordsnoreleasefromthebody)itwouldtakeapproximately438yearsofcumulativecobaltionreleasetocomparewithwhatthebeerdrinkerswereingestingintwomonths!Furthermore,“cancerinhumansasaresultofexposuretocobaltbyanyroutehasnotbeendemonstrated.”30TheUSNationalToxicologyProgramdoesnotlistcobaltasarecognizedanimalorhumancarcinogen.31

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Studiesofelevatedcobaltlevelsinpregnantwomen,andbeerdrinkershavenotdemonstratedanelevatedriskofcancerdespitelevelsmuchhigherthanthosereportedfrommetal-on-metalimplants.

CConcernsregardingthetotalchromiumvaluesreportedinmetal-on-metalionsstudiesshouldbeweighedagainstthedailyvaluesrecommendinotherstudies.

Figure7

Figure8

verybearingsurfaceproducesanenvironmentalburdenofwearrelateddebris,nonebeingtotallyinertinthebody.Occurrenceofosteolysisduetohighermagnitudesofpolythyelenewearhasbeenreportedintheliterature.37,38Metallicparticlesmayalsobeassociatedwithosteolysis,althoughreportsofthisarelacking,andoccurrenceisrare.Ceramicparticleshavebeenassociatedwithosteolysis.Dr.Yoon,etal.,reportedon103ceramic-on-ceramichipsat7.6yearsfollow-up,finding22%femorallysisand49%acetabularlysis.39Somehavesuggestedthatthehighlycrosslinkedpolyethylenesmaynoteliminateosteolysis,inthatincreasedirradiationenergycanleadtosmaller,rounderparticulate40whichhasbeendirectlyassociatedwithanincreasedosteolyticresponse.41,42Areducedlocalresponsetometal-on-metalwearproductshasbeenwelldocumentedintwenty-yearstudiesbySchmidt,McKellop,andCuckler.1,2,43Dr.Cuckler,amongotherresearchers,hassuggestedthatreasonsforthereducedtissueresponseofmetal-on-metalweardebrisareduetoultra-lowmetal-on-metalwearrateswhichreducestheenvironmentalburdenandlocalinflammatoryresponses.43Themajorityofwearproductsexistatasubmicronlevelenablingtheweardebristobeexcretedfromthebodythroughthebody’snormalmetabolicprocesses.ThiswasreportedbyDr.Schaffer;“Weconcludethattheeliminationofcobaltandchromiumproceedsoverseveralyears,affectingabalancebetweenreleaseandexcretion”(Figure9).Thisreleasefromthebodyinanionicformmayavoidalocalresponseaswellanytoxicbuild-uponasystemiclevel.

Concernsregardingionreleasemustbeweighedagainstthewearby-productsofotherbearingsurfaces.

5

E

Everybearingsurfaceproducesanenvironmentalburdenofwearrelateddebris,noneofwhichareinerttothebody.Occurrenceofosteolysisduetoexcesspolythyelenewearisregularlyreportedintheliterature.37,38Reportsofosteolysiswithmetal-on-metalimplantsarerare.

Theexcretionofionsthroughtheurineisevidencedinclinicaltrialsofmetal-on-metalimplantsaslistedabove.

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References:

1.) Schmidt,etal,;“CobaltChromiumMolybdenumMetalCombinationforModularHipProstheses”ClinicalOrthopedicsandRelatedResearch,329,pp35–47,August1996.

2.) McKellop,etal,;“In-VivoWearof3TypesofMetalonMetalHipProsthesesDuringTwoDecadesofUse”ClinicalOrthopedicsandRelatedResearch,329,pp.128–40,August1996.

3.) Rieker,etal.;ClinicalTribologicalPerformanceof144Metal-on-MetalHipArticulations.MetasulaMetal-on-MetalBearing,HansHuberPress,Bern,Germany;pp.83–91,1999.

4.) Jacobsson,etal,;“20-YearResultsofMcKee-FarrarVersusCharnleyProsthesis”ClinicalOrthopedicsandRelatedResearch,329,ppS60–S68,1996.

5.) AmstutzandGrigoris,;“MetalonMetalBearingsinHipArthroplasty”ClinicalOrthopaedicsandRelatedResearch,Number329S,ppS11–S34,1996.

6.) Lombardi,etal:,“Short-TermResultsoftheM2a-TaperMetal-on-MetalArticulation”TheJournalofArthroplasty,Vol.16(8):122–28,December2001.

7.) Dorr,etal,;“ModernMetalonMetalArticulationforTotalHipReplacements”ClinicalOrthopedicsandRelatedResearch,333,pp108–117,1996.

8.) SimulatorDataonFileatBiometInc.9.) Burroughs,B.,Harris,W.,;“FemoralHeadSizeinTHR:RationaleforReassessment”Abstract32ndAnnualAdvancesinHipandKneeArthroplasty,

Cambridge,MAOctober2002.10.) AmstutzHC.,etal.,;“RangeofMotionStudiesforTotalHipReplacements:AComparativeStudywithExperimentalApparatus”,Clinical

OrthopedicsandRelatedResearch,111,pp124–130,1975.11.) Beaule,etal,;“JumboFemoralHeadfortheTreatmentofRecurrentDislocationFollowingTotalHipReplacement”TheJournalofBoneandJoint

Surgery,Vol.84–A:2,pp256–63,February2002.

Conclusion

hereareavarietyofbearingoptionsavailablefortotalhipreplacement.Metal-on-metalisthemostclinicallyprovenalternatebearingavailabletoday,withover40yearsofclinicaluse.Concernsassociatedwithmetalionreleasemustbeweighedagainsttherisksandbenefitsofotherbearingoptions.Metallicdebrisisanenvironmentalby-productofmetal-on-metalwearandispresentinthebodywithnon-metal-on-metalbearingsurfaces.24,33Extensiveresearchandyearsofclinicaltrialshavefailedtoproveanycauseforconcernassociatedwiththeionlevelsexhibitedfrommetal-on-metalimplants.Thelower-wearaspectsandwiderangeofdesignoptionsavailablewithametal-on-metalimplantmakeitparticularlyattractivefortheyounger,moreactivepatientpopulation.

Thelower-wearaspectsandwiderangeofdesignoptionsavailablewithametal-on-metalimplantmakeitparticularlyattractivefortheyounger,moreactivepatientpopulation.

T

11

12.) Komistek,;R.,etal.,“InVivoComparisonofHipSeparationafterMetal-on-MetalorMetal-on-PolyethyleneTotalHipArthroplasty”TheJournalofBoneandJointSurgery,Volume84A:10,pp1836–41,October2002.

13.) Elke,R.,“ParticleDisease:StatusandToday’sSolutions”BioceramicsinJointArthroplasty:Proceedingsofthe7thInternationalBiolox®Symposium,March2002.

14.) Li,S.,“IndependentEvaluationofCrosslinkedPoly”Notes:6thAnnualSymposiumonAlternativeBearingSurfacesinTotalJointArthroplasty,SanFrancisco,CA,September2003.

15.) Tharani,etal.;“TheRiskofCancerFollowingTotalHiporKneeArthroplasty”TheJournalofBoneandJointSurgery,Volume83:5,pp774–80,May2001.

16.) Visuri,etal.;“CancerRiskAfterMetalonMetalandPolyethyleneonMetalTHA”ClinicalOrthopedicsandRelatedResearch,329,pp280–89,August1996.

17.) Merritt,etal.;“DistributionofCobaltChromiumWearandCorrosionProductsandBiologicReactions”ClinicalOrthopedicsandRelatedResearch,329,pp233–43,August1996.

18.) Shaffer,etal.;“IncreasedBloodCobaltandChromiumAfterTotalHipReplacement”ClinicalToxicology,37(7),pp839–44,1999.19.) Brodner,etal,;“ElevatedSerumCobaltwithMetalonMetalArticulatingSurfaces”TheJournalofBoneandJointSurgery,Vol.79-B:2,pp316–21,

March1997.20.) Jacobs,etal,;“CobaltandChromiumConcentrationsinPatientswithMetalonMetalTotalHipReplacements”ClinicalOrthopedicsandRelated

Research,329,pp256–63,August1996.21.) MacDonaldetal,;“MetalonMetalVersusMetalonPolyethyleneLinersinTHA:ClinicalandMetalIonResultsofaProspectiveRandomized

ClinicalTrial”HipSocietyAbstract,February2002.22.) Skipor,A,etal.,“MetalLevelsinPatientswithMetal-on-MetalTotalHipReplacements.”Abstract;69thAnnualMeetingProceedingsoftheAAOS,

PaperNo.166Vol.3,Dallas,TX2002.23.) Venable,C.S.,andStuck,W.G.:J.A.M.A.111:1349,1938.24.) Kriebich,D,etal.,“SystemicReleaseofCobaltandChromiumAfterUncementedTotalHipReplacement.”TheJournalofBoneandJointSurgery

(Br)1996;78–B:18–21.25.) Maloney,WJ.:“CeramicBearings:America,YouArrived!–SomeCons”SessionXVPaper#64CurrentConceptsinJointReplacement,May2003.26.) Aitio,A.;“StainlessSteelKitchenUtensilsasaSourceofChromium–ToxicologicalImplications”TheChromiumFile:TheInternational

ChromiumDevelopmentAssociationIssue#1September1996.27.) Proctoretal.IsHexavalentChromiumCarcinogenicViaIngestion?AWeightofEvidenceofReview.JournalofToxicologyandEnvironmental

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