3/4/2015 Bonecement

JClinOrthopTrauma.2013Dec4(4):157163. PMCID:PMC3880950
Publishedonline2013Dec15.doi:10.1016/j.jcot.2013.11.005

Bonecement
RajuVaishya,(MS,MCh,FRCS), a, MayankChauhan,(MSOrth), bandAbhishekVaish,(MBBS)c
a
Prof,SeniorConsultant,DepartmentofOrthopaedic&JointReplacementSurgery,IndraprasthaApolloHospitals,NewDelhi,India
b
OrthopaedicRegistrar,DepartmentofOrthopaedic&JointReplacementSurgery,IndraprasthaApolloHospitals,NewDelhi,India
c
PostGraduateStudent(Orthopaedics),DepartmentofOrthopaedics,SanchetiInstituteofOrthopaedics,Pune,India
RajuVaishya:raju.vaishya@gmail.com
Correspondingauthor.Email:raju.vaishya@gmail.com

Received2013Nov6Accepted2013Nov21.

Copyright2013DelhiOrthopedicAssociation.PublishedbyElsevierB.V.Allrightsreserved.

Abstract Goto:

TheknowledgeaboutthebonecementisofparamountimportancetoallOrthopaedicsurgeons.Althoughthebone
cementhadbeenthegoldstandardinthefieldofjointreplacementsurgery,itsusehassomewhatdecreased
becauseoftheadventofpressfitimplantswhichencouragesboneingrowth.Theshortcomings,sideeffectsand
toxicityofthebonecementarebeingaddressedrecently.Moreresearchisneededandcontinuesinthefieldof
nanoparticleadditives,enhancedbonecementinterfaceetc.

Keywords:Bonecement,Jointreplacement,Arthroplasty,Antibiotic,Viscosity

1.Introduction Goto:

Polymethylmethacrylate(PMMA),iscommonlyknownasbonecement,andiswidelyusedforimplantfixationin
variousOrthopaedicandtraumasurgery.Inreality,cementisamisnomerbecause,thewordcementisusedto
describeasubstancethatbondstwothingstogether.However,PMMAactsasaspacefillerthatcreatesatight
spacewhichholdstheimplantagainsttheboneandthusactsasagrout.1Bonecementshavenointrinsicadhesive
properties,buttheyrelyinsteadonclosemechanicalinterlockbetweentheirregularbonesurfaceandthe
prosthesis.Othertypesofcommerciallyavailablebonecementlikecalciumphosphatecements(CPCs)andGlass
polyalkenoate(ionomer)cements(GPCs)aresuccessfullyusedinavarietyoforthopaedicanddentalapplications.
CPCsarebioresorbableandbiocompatible,butaremainlyusedincranialandmaxillofacialsurgeriesbecauseof
theirlowmechanicalstrength.2

Eventhoughtheusesandavailabilityofvarioustypesofbonecementhasgreatlyevolvedoverthepastcentury,
furtherresearchstillcontinuestodevelopitsmoreclinicalapplicationsandtoreducetheadverseeffectsassociated
withtheiruse.

2.Historicalperspective Goto:

ThemistoklesGluck(1870),hadfixedatotalkneeprosthesismadeofivoryusingcementmadeofplasterand
colophony.3OttoRohmandKulzerwereearlypioneerswhoworkedextensivelyonthephysicalpropertiesand
usesofbonecement.TheeraofmodernPMMAbonecementscomesfromthepatentbyDegussaandKulzer
(1943),whohaddescribedthemechanismofpolymerizationofmethylmethacrylate(MMA)atroomtemperatureif
acoinitiator,suchasatertiaryaromaticamine,isadded.4

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ThefirstbonecementuseinOrthopaedicsiswidelycreditedtothefamousEnglishsurgeon,JohnCharnley,who
in1958,useditfortotalhiparthroplasty.5HehadusedcoldcuredPMMAtoattachanacryliccuptothefemoral
headandtoseatametallicfemoralprosthesis.ThiswasasignificantmilestoneintheadvancementofOrthopaedic
surgicalprocedures.Also,CharnleywasthefirsttorealizethatPMMAeasilycouldbeusedtofillthemedullary
canalandiseasytoblendwiththebonemorphology.

Inthe1970's,theU.S.FoodandDrugAdministration(FDA)approvedbonecementforuseinhipandknee
prostheticfixation.6Sincethen,whilebonecementhasbecomewidelyusedforfixationofprosthesestoliving
bone,thetrendsofbonecementusagehaveevolved.

3.PMMAconstituents Goto:

PMMAisanacrylicpolymerthatisformedbymixingtwosterilecomponents(Table1):aliquidMMAmonomer
andapoweredMMAstyrenecopolymer.7Whenthetwocomponentsaremixed,theliquidmonomerpolymerizes
aroundtheprepolymerizedpowderparticlestoformhardenedPMMA.Intheprocess,heatisgenerated,duetoan
exothermicreaction.

Table1
Constituentsofbonecement.

PMMA,alongwiththepresenceofvariousadditives,givesthemixtureasetofphysicalandchemicalproperties.3
Exposuretolightorhightemperaturescancauseprematurepolymerizationoftheliquidcomponent.Hydroquinone
thereforeisaddedasastabiliserorinhibitortopreventprematurepolymerization.Aninitiator,dibenzoylperoxide
(BPO),isaddedtothepowder,andanaccelerator,mostlyN,Ndimethylptoluidine(DmpT),isaddedtothe
liquidtoencouragethepolymerandmonomertopolymeriseatroomtemperature(coldcuringcement).

Inordertomakethecementradiopaque,acontrastagentisadded.Commerciallyavailablecementsuseeither
zirconiumdioxide(ZrO2)orbariumsulphate(BaSO4).Zirconiumdioxideisonehundredtimeslesssolublethan
bariumsulphateandhaslesseffectonthemechanicalpropertiesofthecement.

Duringtheexothermicfreeradicalpolymerizationprocess,thecementheatsup.Thispolymerizationheatreaches
temperaturesofaround8286Cinthebody.Thecauseofthelowpolymerizationtemperatureinthebodyisthe
relativelythincementcoating,whichshouldnotexceed5mm,andthetemperaturedissipationviathelarge
prosthesissurfaceandtheflowofblood.8

3.1.Antibioticbonecement

Bonecementhasprovenparticularlyusefulbecausespecificactivesubstances,e.g.antibiotics,canbeaddedtothe
powdercomponent.Thismakesbonecementamoderndrugdeliverysystemthatdeliverstherequireddrugs
directlytothesurgicalsite.Thelocalactivesubstancelevelsofbonecementsaresignificantlybelowtheclinical
routinedosagesforsystemicsingleinjections.Researchhasshownthataddingvarioustypesofantibioticstobone
cement,inquantitieslessthan2gperstandardpacketofbonecement,doesnotadverselyaffectsomeofthe
cement'smechanicalproperties(compressiveordiametricaltensilestrengths),althoughquantitiesexceeding2gdid
weakenthem.9VariousantibioticshavebeensuccessfullymixedandusedwithbonecementslikeGentamycin,
Tobramycin,Erythromycin,Cefuroxime,Vancomycin,Colistinetc.Thebasicrequirement,beingthatthemixable
antibioticshouldbeheatresistantandshouldlastforlongerdurationoftime.

Gentamycin,whenusedincombinationwithtobramycin,showsasynergisticeffect,witha68%greaterelutionof
tobramycin(P=0.024),and103%greaterelutionofvancomycinfromthebonecement(P=0.007),comparedto
controlscontainingonlyoneantibiotic.10

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vanStadeninhisstudyreportedthatBacteriocinsmaybeapossiblealternativetoantibioticsincorporatedintobone
cement.Theinvitroresultsofthestudyshowedthatbacteriocinsincorporatedintobrushitecementdidnot
significantlyalterthecharacteristicsofthematrixandthatthepeptideswerereleasedinanactiveform.Finallyit
wasshownthatnisinFloadedbrushitecementcontrolledS.aureusinfectioninmice.11

Silvercontainingnanoparticleshavealsoshownpromiseaseffectiveantibacterialagentswhichcanbeaddedto
bonecement.12VitaminEadditives(10%)haveshownapositiveeffectonfreeradicaloxidationandexothermic
activity,withonlymodestreduction(<5%)intensilestrength.4

Comparedtointramuscularadministration,systemicconcentrationlevelsofGentamycinarelowwithbonecement,
usualmaximumlevelbeing<1g/ml(<10%).Therearenodetectablesystemiclevelsaftersevendaysfrom
administration.Gentamycinlevelsinurineafterbonecementadministrationrangefrom10g/mlinitiallyto1
2g/mlaftersevendays.

Differentbonecementshavedifferentchemicalformulations,givingarangeofantibioticbonecementswith
varyinghandlingcharacteristics,whicharesuitedtoabroadrangeofclinicalrequirementsandsurgicaltechniques.

3.2.Usageandproperties

SinceCharnleyfirstbeganusingacrylicbonecementinhiparthroplasty,therehavebeenanumberof
developmentsintheusageandpropertiesofbonecement.

3.3.Curingprocess

Thecuringprocessisdividedinto4stages:a)mixing,b)sticky/waiting,c)working,andd)hardening.Themixing
canbedonebyhandorwiththeaidofcentrifugationorvacuumtechnologies.

Bonecementsareheatsensitive.Anyincreaseordecreaseintemperature(eitherambient,and/orofthecement
componentsandmixingequipment)fromtherecommendedtemperatureof73F(23C)affectsthehandling
characteristicsandsettingtimeofthecement.Manualhandlingandbodytemperaturereducesthefinalsettingtime.
Variationsinhumidityaffectthecementhandlingcharacteristicsandsettingtime.Itisrecommendedthatthe
unopenedcementcomponentsarestoredat73F(23C)foraminimumof24hbeforeuse.Vacuummixingof
cementcanalsoacceleratethesettingtimeofthecement.

Highviscositycementsaresometimesprechilledforusewithmixingsystemsforeasiermixingandprolonged
workingphase.Thiswillalsoincreasethesettingtime.Therelativehumiditymightalsoinfluencethehandling
properties.Thatisthereasonwhytheworkingtimeandsettingtimeofthecementmightvaryinwinterand
summer.

UnlikethepolymerizationreactionofPMMA,calciumphosphatecementsarehardenedthroughadissolutionand
precipitationprocessthatproduceshardeningwithentanglementofprecipitatedcrystals.2

4.Methodsofapplication Goto:

Variousmethodsexistfortheapplicationofcementintotheboneorjointsurface.13

4.1.Digital

Allantibioticbonecementscanbeapplieddigitally.Thecementismixedthoroughlybutcarefullytominimizethe
entrapmentofair.Oncedoughisformedthesurgeonshouldwaituntilthecementnolongeradherestotheglove
andthesurfacehasbecomedullasopposedtoshiny.Thecementcanthenbetakenintoglovedhandsandkneaded
thoroughly.Itisvitalthatprematureinsertionofcementisavoidedasthismayleadtoadropinthepatient'sblood
pressure.Importantly,thisstagewilloccuratdifferenttimesfordifferentcementtypes.

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Thetimeofcementapplicationandprosthesisinsertionisatthediscretionofthesurgeonandwilldependuponthe
surgicalprocedureused.Ingeneral,implantinsertionshouldbedelayeduntilthecementhasdevelopedasufficient
degreeofviscositytoresistexcessivedisplacementbytheimplant.However,implantinsertionshouldnotbe
delayedsuchthatthereisariskthattheprocedurecannotbecompletedduetocementhardening.

Followingintroductiontheimplantmustbefirmlyheldinpositiontoavoidmovementandpressurizationmustbe
maintaineduntilthecementfinallyhardens.Excessbonecementmustberemovedbeforethecementhas
completelyhardened.

4.2.Syringeapplication

Gentamycinantibioticbonecementsmaybeappliedusingasuitablecementgunandsyringe(Fig.1).Thesurgeon
shouldusetheirexperiencetojudgewhenthecementhasreachedanappropriateviscositytobeextruded.Thiswill
notoccuruntilafterthecementhasformeddough.Asmallamountofcementshouldbeextrudedfromthesyringe
andvisuallyassessedtoensurethatthesurfaceofthecementappearsdullandexcessiveflowundergravityhas
ceased.

Fig.1
Powderandliquidcomponentsofbonecement.

Priortoextrusion,itisrecommendedthatacementrestrictorbeinserted,attherequireddepthinto,theprepared
bonecavity.14Introductionofbonecementintothepreparedcavityshouldbecarriedoutinaretrogradefashion.
Oncethecavityisfilleditisadvisablethatadequatepressurizationisappliedandmaintaineduptothepointof
hardening.

4.3.Vacuummixing&delivery

Vacuummixing,whichwasadaptedfromthedentalfield,wasdevelopedforbonecementintheearly1980s.
Vacuummixingreducesbonecementporosityandreducesmonomerevaporationandexposureintheoperating
room.

Mixingaswellascollectingcementundervacuumyieldsahomogenousmixwithoutaffectingviscosityorother
propertiesofthecement.15

4.4.Pressurization

Thepressureappliedtothecementhastobelargerthanthebloodpressuresoasnottobepushedoutofthebone.
Pressureshouldbeapplieduntiltheviscosityofthebonecementhasincreasedsoitishighenoughtoresistblood
pressure.Manystudiesstatethatpressurizationresultsingreaterpenetrationofthebone,improvesbonecement
interfaceandincreasesfatiguestrengthofthecement.Whenpressurizingthecementinthefemur,apositivesignof
pressurizationismarrowextrusioninthegreatertrochanter(thesocalledsweatingtrochantersign).16

4.5.Viscosity

Mixingtogetherthepowderandtheliquidcomponentsmarksthestartofthepolymerizationprocess.Duringthe
reaction,thecementviscosityincreases,slowlyatfirst,thenlatermorerapidly(Fig.2).Studieshaveshownthat
highviscositycementsresultinbetterprostheticfixation,ascomparedtolowviscositycements.17

Fig.2
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Mixingofbonecement.

Bonecementsmaybedividedintothreekinds:low,mediumandhighviscosity.

Lowviscosity:thesecementshavealonglastingliquid,ormixingphase,whichmakesforashortworkingphase.
Asaconsequence,applicationoflowviscositycementsrequiresstrictadherencetoapplicationtimes.

Highviscosity:thesecementshaveashortmixingphaseandlosetheirstickinessquickly.Thismakesforalonger
workingphase,givingthesurgeonmoretimeforapplication.

Idealviscositywillbehighenoughtoavoidanycementmixingwithbloodorfat/bonymaterialfromthe
implantationregionyetlowenoughtopenetratetheboneadequately.

4.6.Stemcentralizer

Femoralstemcentralizerswereoriginallydesignedfordoubletapered,straightstems.18Astemcentralizer(Fig.3)
guidesthefemoralprosthesistoaneutralpositionwithinthecementandguaranteesanevencementlayerbetween
theboneandprosthesis.19

Fig.3
Distalcentralizer.

Thicknessofthecementmantlearoundanyshaftshouldbeapproximately3mmtoprovidesufficientmechanical
strength.Spacersontheacetabularcupwillensureanevencementlayeraroundthecup.Thecementmantleshould
be23mm,yieldingbetterstressdistribution.

Thedistalcementcentralizeriswidelyusedandisassumedtobevaluableinaffectingthequalityofcementedtotal
hipreplacement.Theliteraturesuggeststhattheuseofthedistalcentralizerimprovesthequalityofthedistalmantle
aswellasimprovesstemposition.19However,somestudiesdisputethesame.18

4.7.Cementrestrictors

Theuseofintramedullaryplugsincementedtotaljointarthroplastyisnowconsideredaroutinepracticebymost
surgeons.Inordertoachievegoodfillingandpressurizationinhip,asmallpieceofboneoracementrestrictormay
beusedtoplugtheshaft.Therestrictorshouldbeplacednomorethan2cmdistaltotipofthestem.

Theprimarygoalofpluggingtheintramedullarycanalduringtotalhiparthroplastyistoincreasepenetrationof
cementintothecancellousboneproximaltotheintramedullaryplug.Thisrecallsingreaterpenetrationandmay
enhanceprostheticstability.

5.Bonebedpreparation Goto:

5.1.Microinterlock

Theconceptofmicrointerlockisapositivecontributiontothequalityoffixations.Theinterfacestrengthisnot
onlyaffectedbythedegreeofcementpenetrationbutalsobythequalityofthecancellousframework.Theaddition
ofhydroxyapatite(HA)enhancestheconnectiontothebonesinceHAisthemaininorganicconstituentofbone
tissue,althoughthiscompromisesthemechanicalstrengthofthecement.20

Thereareanumberofessentialprerequisitesforsuccessfulmicrointerlock:
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1. Thoroughlycleanedbonebed,brushandlavagebeforeapplyingthecement.
2. InjectingthecementuntilitisofhighviscosityItpreventsthebloodfrompenetratingintothecementand
therebyweakeningit.
3. Pressurizethecementbyusingacementgunandsealingoffthebonecavity.

Carefulpreparationofthebonecavityandbonebedwithhighpressurepulselavageandbrushingisessentialfor
achievinganeffectivemicrointerlockbetweentheboneandthecement.

5.2.Reaming

Thebonecavityshouldbeshapedtoprovideanevencementlayerbetweentheboneandprosthesis.Sizeof
reamingshouldbedeterminedatpreoperativeplanning.

5.3.Brushing

Mechanicalcleaningwithabrushisrecommended.Accidentalintroductionofbloodandtissuedebrisintothe
cementmaycauselaminations,whichcanlowertheeffectivestrengthofthebonecement.Acetabularandfemoral
brushesareusedtoremovesofttissueandloosecancellousbonefromthecavity.

5.4.Pulselavage

Usinghighpressurepulselavage(Fig.4)toremoveremainingboneparticlesanddebrisinajointarthroplasty
producesacleansurface.Theriskofbloodlaminationisreducedandthemechanicalstrengthofthecementis
increased.Microinterlockbetweentheboneandthecementisachievedbyhighpressurepulselavage
repeatedly.21

Fig.4
Pulselavage.

Astudyconcludedthatmeticuloushighvolumehighpressurepulsatilelavagereducesbothpulmonary
physiologicalderangementsandfatemboli.22

5.5.Anchorageholesintheacetabulum

Theanchorageholesaremadeinordertoremoveaslittleboneaspossibleandtheymaybedrilledand/or
impacted.Anchorageholesincreasethecontactareabetweenboneandcement,providingforbetterfixation(Fig.5
).

Fig.5
Cementedacetabularcomponent.

6.Evolutionofcementingtechniques Goto:

Overall,advancementsincementingcanbeclassifiedtohaveoccurredfromfirstgenerationtothirdgeneration
techniques,withchangesoccurringinbonebedpreparation,cementpreparationandcementdelivery.23,24

6.1.Firstgenerationcementingtechnique

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Itinvolvedthehandmixingofcementinbowels.Therewasonlyaminimalpreparationofthefemoralcanaland
cancellousbonewasleftinsitu.Thecanalwasirrigatedandsuctionedpriortothedigitalapplicationofcement.
Theprosthesiswastheninsertedintothefemoralcanal.Duringthe1980'sthesetechniqueswererefined.Steps
weretakentoreducetheporosityofthecementandtherebyincreasethefatiguelife.Pressurizationofthecement
wasintroducedtoimproveosseointegrationofthecementandtheimportanceofagoodcementmantlearoundthe
prosthesiswasmoreclearlyunderstood.

6.2.Secondgenerationcementingtechniques

Allcancellousboneisremovedasneartotheendostealsurfaceanddistalcementrestrictorwasalsoused.Thereis
pulsatileirrigation,packinganddryingofthefemoralcanalfollowedbyretrogradeinsertionofcementwitha
cementgun.Theprosthesisisagainpositionedmanually.25Furtherimprovementleadtothedevelopmentofthird
generationcementingtechniques.

6.3.Thirdgenerationcementingtechniques

Cementisnowpreparedusingavacuumcentrifugation,whichfurtherreducesporosity.Thefemoralcanalis
irrigatedwithpulsatilelavageandthenpackedwithadrenalinesoakedswabs.Afterinsertionofthecementina
retrogradefashion,thecementispressurised.Finallytheprosthesisisinsertedusingdistalandproximalcentralizers
toensureanevencementmantle(4thgeneration).

7.Cautionandadverseeffects Goto:

Hypotensiveepisodesandcardiacarresthavebeenreportedduringcementinsertion.26

Pressurizationandthoroughcleaningofthebonewithexpulsionofbonemarrowhasbeenassociatedwiththe
occurrenceofpulmonaryembolisms,andthisriskhasbeenfoundtobeincreasedinpatientswithhighly
osteoporoticboneandpatientsdiagnosedwithfemoralneckfracture.Reamingofthemarrowcavitycanhave
similareffectsonmeanarterialpressureastheintroductionofthebonecement.Marrowcavitiesshouldbevented
whenthecementisintroduceddigitally.Theprematureinsertionofbonecementmayleadtoadropinblood
pressure,whichhasbeenlinkedtotheavailabilityofmethylmethacrylateatthesurfaceoftheproduct,27although
thishasnotbeenproven.Thisdropinbloodpressure,ontopofhypotensioninducedeitheraccidentallyor
intentionally,canleadtocardiacarrhythmiasortoanischaemicmyocardium.However,accordingtoareport,the
possibleriskofdeathassociatedwiththeuseofcementedimplantisconfinedtoearlypostoperativeand
perioperativeperiod.28

Thehypotensiveeffectsofmethylmethacrylatearepotentiatedifthepatientissufferingfromhypovolaemia.

Themostfrequentadversereactionsreportedwithacrylicbonecementsare:

Transitoryfallinbloodpressure.
Elevatedserumgammaglutamyltranspeptidase(GGTP)upto10dayspostoperation.
Thrombophlebitis.
Looseningordisplacementoftheprosthesis.
Superficialordeepwoundinfection.
Trochantericbursitis.
Shorttermcardiacconductionirregularities.
Heterotopicnewboneformation.
Trochantericseparation.

7.1.Otherknownadverseeffects29,30

BCIS(Bonecementimplantationsyndrome)ischaracterizedbyanumberofclinicalfeaturesthatmay
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includehypoxia,hypotension,cardiacarrhythmias,increasedpulmonaryvascularresistance(PVR)and
29Itusuallyoccursat
cardiacarrest.Itismostcommonlyassociatedwith,butisnotrestrictedto,hiparthroplasty.
oneofthefivestagesinthesurgicalprocedurefemoralreaming,acetabularorfemoralcementimplantation,
insertionoftheprosthesisorjointreduction.Itisanimportantcauseofintraoperativemortalityandmorbidity
inpatientsundergoingcementedhiparthroplastyandmayalsobeseeninthepostoperativeperiodinamilder
formcausinghypoxiaandconfusion.
Hypoxaemia.
Cardiacarrhythmia.
Bronchospasm.
Adversetissuereaction.
Haematuria.
Dysuria.
Bladderfistula.
Localneuropathy.
Localvascularerosionandocclusion.
Transitoryworseningofpainduetoheatreleasedduringpolymerization.
Delayedsciaticnerveentrapmentduetoextrusionofthebonecementbeyondtheregionofitsintended
application.
Intestinalobstructionbecauseofadhesionsandstrictureoftheileumduetotheheatreleasedduringcement
polymerization.

8.Drawbacksofbonecement Goto:

Oneofthemajordrawbacksofbonecementinjointreplacementiscementfragmentationandforeignbody
reactiontoweardebris,resultinginprostheticlooseningandperiprostheticosteolysis.Theproductionofwear
particlesfromroughenedmetallicsurfacesandfromthePMMAcementpromoteslocalinflammatoryactivity,
resultinginchroniccomplicationstohipreplacements.Histologically,alayerofsynoviallikecellswhichlinethe
bonecementinterfacesupportedbyastromacontainingmacrophagesandwearparticles,hasbeendescribedin
looseprostheses.31Athirdofdensefibroustissuecontainspolymethylmethacrylate,polyethyleneandmetallic
debris.Activatedmacrophagesexpresscytokinesincludinginterleukin1,interleukin6andtumournecrosisfactor
alpha,whichmediateperiprostheticosteolysis.

Bonecementgeneratesheatasitcuresandcontractsandlaterexpandsduetowaterabsorption.Itisneither
osteoinductivenorosteoconductiveanddoesnotremodel.

Themonomeristoxicandthereisapotentialforallergicreactionstocementconstituents.

9.Conclusion Goto:

TheknowledgeaboutthebonecementisofparamountimportancetoallOrthopaedicsurgeons.Althoughthebone
cementhadbeenthegoldstandardinthefieldofjointreplacementsurgery,itsusehassomewhatdecreased
becauseoftheadventofpressfitimplantswhichencourageboneingrowth.Theshortcomings,sideeffectsand
toxicityofthebonecementarebeingaddressedrecently.Moreresearchisneededandcontinuesinthefieldof
nanoparticleadditives,enhancedbonecementinterfaceandotherdevelopmentsinquestforimprovingthequality
andeliminatingorreducingundesiredsideeffectsofbonecement.

Conflictsofinterest Goto:

Nobenefitsinanyformhavebeenreceivedorwillbereceivedfromacommercialpartyrelateddirectlyor
indirectlytothesubjectofthisarticle.

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