http://www.diva-portal.org Postprint This is the accepted version of a paper published in Biomechanics and Modeling in Mechanobiology. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Citation for the original published paper (version of record): Ajaxon, I., Persson, C. (2014) Compressive fatigue properties of a commercially available acrylic bone cement for vertebroplasty. Biomechanics and Modeling in Mechanobiology, 13(6): 1199-1207 http://dx.doi.org/10.1007/s10237-014-0566-8 Access to the published version may require subscription. N.B. When citing this work, cite the original published paper. Permanent link to this version: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233740 Compressive* fatigue* properties* of* a* commercially* available* acrylic* bone*cement*for*vertebroplasty* Ingrid!Ajaxon1,!Cecilia!Persson1,*! 1Division! of! Applied! Materials! Science,! Department! of! Engineering! Sciences,! Uppsala!University,!Box!534,!751!21!Uppsala,!Sweden! ! *Corresponding!author:! EKmail:[email protected]! Telephone:!+46!(0)!18!471!79!11! Postal!address:!The!Ångström!Laboratory,!Department!of!Engineering!Sciences,! Applied!Materials!Science,!Box!534,!SEK751!21!UPPSALA,!SWEDEN! ! * ! 1! Abstract* Acrylic!bone!cements!are!widely!used!for!fixation!of!joint!prostheses!as!well!as! for! vertebral! body! augmentation! procedures! of! vertebroplasty! and! balloon! kyphoplasty,!with!the!cement!zone(s)!being!subjected!to!repeated!mechanical! loading!in!each!of!these!applications.!Although,!in!vertebroplasty!and!balloon! kyphoplasty,!the!cement!zone!is!exposed!to!mainly!cyclical!compressive!load,!the! compressive!fatigue!properties!of!acrylic!bone!cements!used!in!these!procedures! are!yet!to!be!determined.!The!purposes!of!the!present!study!were!to!determine! the!compressive!fatigue!properties!of!a!commercially!available!cement!brand! used!in!vertebroplasty,!including!the!effect!of!frequency!on!these!properties;!to! identify! the! cement! failure! modes! under! compressive! cyclical! load;! and! to! introduce!a!screening!method!that!may!be!used!to!shorten!the!lengthy!character! of!the!standardized!fatigue!tests.!Osteopal®V!was!used!as!the!model!cement!in! this!study.!The!combinations!of!maximum!stress!and!frequency!used!were:!50.0,! 55.0,!60.0,!62.5!and!75.5!MPa!at!2!Hz;!and!of!40.0,!55.0,!60.0,!62.5!or!75.5!MPa!at! 10!Hz.!Through!analysis!of!nominal!strainKnumber!of!loading!cycles!results,!three! cement!failure!modes!were!identified.!The!estimated!mean!fatigue!limit!at!2!Hz! (55.4!MPa)!was!significantly!higher!than!that!at!10!Hz!(41.1!MPa).!The!estimated! fatigue!limit!at!2!Hz!is!much!higher!than!stresses!commonly!found!in!the!spine! and!also!higher!than!that!for!other!acrylic!bone!cements!tested!in!a!full!tensionK compression! fatigue! test,! which! indicates! that! tensionKcompression! fatigue! testing!may!substantially!underestimate!the!performance!of!cements!intended! for!vertebroplasty.!A!screening!method!was!introduced,!that!may!be!used!to! shorten!the!time!spent!in!performing!compressive!fatigue!tests!on!specimens!of! acrylic!bone!cement!for!use!in!vertebral!body!augmentation!procedures.! ! Highlights* • Compressive!fatigue!properties!of!a!commercially!available!acrylic!bone! cement!brand!used!in!VP!were!determined.!! • Three!failure!modes!were!found,!the!details!of!which!depend!on!applied! frequency!and!stress.! ! 2! • The!estimated!mean!fatigue!limit!at!a!frequency!of!2!Hz!was!significantly! higher!than!that!at!10!Hz.! • Full!tensionKcompression!fatigue!testing!may!underestimate!the!cements’! performance!in!vertebroplasty.! • A! screening! method! is! introduced! that! may! be! used! to! shorten! the! duration!of!compressive!fatigue!tests.! ! Keywords* Acrylic!bone!cement;!vertebroplasty;!compressive!fatigue!properties! ! 1. Introduction* Acrylic!bone!cements!based!on!poly(methyl!methacrylate)!(PMMA)!are!widely! used!in!total!joint!replacements!(TJRs)!as!well!as!in!vertebral!augmentation! procedures!known!as!vertebroplasty!(VP)!and!balloon!kyphoplasty!(BKP),!used! for!pain!relief!and!fracture!stabilization!in!the!spine.!The!use!of!these!types!of! cements!in!TJRs!dates!back!to!the!1960s!(Charnley!1960)!and!in!the!spine!to!the! 1980s,!when!they!were!introduced!as!a!treatment!for!hemangioma!(Galibert!et! al.!1987).!In!all!the!aforementioned!applications,!the!bone!cement!is!subjected!to! repeated!mechanical!loading,!and,!thus,!its!fatigue!properties!are!important!to! the!longKterm!success!of!the!implant.!Whereas!the!fatigue!properties!of!acrylic! bone!cements!used!in!TJRs!have!been!extensively!investigated!(Charnley!1960;! Lewis!2003),!there!are!very!few!reports!on!the!fatigue!properties!of!acrylic!bone! cements!used!in!VP!and!BKP,!despite!the!fact!that!the!composition!of!the!cements! may!differ!substantially.!In!particular,!the!amount!of!radiopacifier,!commonly! BaSO !or!ZrO ,!is!much!higher!in!cements!intended!for!use!in!VP!and!BKP.!Since,! 4 2 in!VP!and!BKP,!a!very!high!level!of!visualization!of!the!cement!is!necessary,!a! radiopacifier!content!of!the!cement!of!between!30!and!45!wt%!(of!the!powder! mass),!is!used!rather!than!the!9!–!15!wt%!used!in!cements!for!TJRs,!and!this! difference!could!be!of!importance!as!far!as!fatigue!performance!of!the!cement!is! concerned!(Galibert!et!al.!1987;!Lewis!2006).!To!the!best!of!the!present!authors’! knowledge,!there!are!only!four!peerKreviewed!reports!available!on!the!fatigue! ! 3! properties!of!acrylic!bone!cement!alone!intended!for!use!in!VP!and!BKP!(Kurtz!et! al.!2005;!Boelen!et!al.!2008;!Lewis!et!al.!2009a;!Köster!et!al.!2013).!Kurtz!et#al.! and!Köster!et#al.!did!not!report!the!fatigue!limit!but!the!other!two!studies!found! results!for!the!mean!fatigue!limit!at!1.5K2!million!cycles!(the!fatigue!limit!is! defined!as!the!cyclic!stress!level!that!can!be!applied!to!the!material!without! causing!failure!at!5!million!cycles!in!ASTM!F2118K03!(ASTM!2009))!of!6.8!–!10.4! MPa!(95%!confidence!bounds!2.8!–!12.8!MPa)!(Boelen!et!al.!2008;!Lewis!et!al.! 2009a),!similar!to!previous!reports!on!the!mean!fatigue!limit!of!cements!used!in! TJRs!(8.1!–!13.1!MPa,!95%!confidence!bounds!were!not!reported!(Lewis!and! Austin! 1994;! Lewis! and! Mladsi! 1998;! Lewis! 2000)).! However,! in! the! above! mentioned! studies,! either! fullyKreversed! tensionKcompression! was! applied! (Kurtz!et!al.!2005;!Boelen!et!al.!2008;!Lewis!et!al.!2009a),!as!specified!in!the! ASTM!standard!for!fatigue!testing!of!acrylic!bone!cement!materials!(ASTM!2009),! or!fourKpoint!bending!(Köster!et!al.!2013),!in!accordance!with!the!ISO!standard! for!flexural!fatigue!testing!of!acrylic!resin!cements!(ISO!2008).!! The!ASTM!standard!for!fatigue!testing!of!acrylic!bone!cement!materials!was! developed!for!cements!used!in!joint!fixations.!In!the!vertebral!body,!however,! mainly! compressive! loads! are! experienced! (Wilke! et! al.! 1999;! Lewis! et! al.! 2009b),!and!a!more!relevant!way!of!fatigue!testing!may!be!under!compression! loading.!Furthermore,!a!previous!study!comparing!cyclic!zeroKtension!loading!to! tensionKcompression!found!that!the!effect!of!compression!on!the!fatigue!strength! appeared! negligible! during! fully! reversed! testing,! indicating! that! cyclic! compression!only!may!give!very!different!results!(Gates!et!al.!1983).!Moreover,! the!standardized!number!of!runKout!cycles!of!5!million!relates!to!testing!of! materials!intended!for!joint!and!hip!replacements,!and!may!be!less!relevant!for! materials!intended!for!VP!and!BKP!(Lewis!et!al.!2008;!ASTM!2009).!! Purely!compressive!fatigue!studies!on!acrylic!bone!cement!(Serbetci!et!al.!2004)! or!PMMA!(Rubiolo!and!Muar!1996;!Rittel!2000)!are!also!scarce!and!none!has! investigated! the! fatigue! limit,! nor! vertebroplastic! cements! containing! high! amounts! of! radiopacifier.! The! only! peerKreviewed! report! available! on! compressive!fatigue!properties!of!an!acrylic!bone!cement!intended!for!BKP!is! from!a!synthetic!bone!augmentation!model,!where!the!combined!performance!of! ! 4! the!cement/synthetic!bone!was!evaluated,!i.e.!not!the!performance!of!the!cement! as! a! standKalone! material! (Lewis! et! al.! 2008).! It! was! found! that! the! acrylic! cement/synthetic! bone! model! survived!one!million!cycles! (runKout)! under! a! compressive!load!of!3.4!MPa.! Due!to!the!lengthy!character!of!fatigue!tests!(the!ASTM!standard!cites!runKout!at! 5!million!cycles,!at!a!frequency!of!2!Hz!(ASTM!2009),!thus,!approximately!29! days!of!testing)!there!is!incentive!to!use!higher!frequencies.!However,!the!fatigue! properties! of! PMMA! may! differ! depending! on! the! frequency;! an! increase! in! fatigue!life!has!been!observed!with!a!higher!frequency!in!tensionKcompression! for!some!cement!brands!(Lewis!2003),!whereas!for!other!brands,!the!influence!of! the!frequency!on!fatigue!life!was!not!significant!(Lewis!et!al.!2003).!However,! where!failure!is!mainly!due!to!thermal!softening,!which!may!be!the!case!under! compressive! loading! (Rittel! 2000),! an! increased! frequency! may! lead! to! a! decrease!in!fatigue!life.!Furthermore,!there!are!no!studies!in!the!literature!on!the! modes!of!cement!failure!in!a!fatigue!test!of!acrylic!bone!cement,!nor!on!a!method! that!may!be!used!to!shorten!the!duration!of!fatigue!testing!on!cement!specimens.! The!purposes!of!the!present!study!were!to!1)!obtain!the!compressive!fatigue! properties!of!a!commercially!available!acrylic!bone!cement!used!in!VP,!at!test! frequencies!of!2!and!10!Hz,!and!hence!determine!the!influence!of!frequency!on! these!properties;!2)!identify!the!failure!modes!of!the!cement;!and!3)!introduce!a! method!that!may!be!used!to!shorten!the!duration!of!compressive!fatigue!tests!on! acrylic!bone!cement!specimens.! ! 2. Materials*and*methods* The!acrylic!cement!Osteopal®V!(Heraeus!Medical!GmbH,!Wehrheim,!Germany),! was!used!as!the!model!cement!in!this!study.!This!cement!has!been!developed!for! use! in! VP! and! its! powder! constituents! are! poly(methyl! acrylate,! methyl! methacrylate)! beads,! benzoyl! peroxide,! ZrO ! (45! wt%),! and! chlorophyll;! its! 2 liquid! constituents! are! methyl! methacrylate! monomer,! N,N! diKmethylKpK toluidine,!hydroquinone,!and!chlorophyll.!! ! 5! The!cement!was!stored!at!room!temperature.!A!spatula!was!used!to!manually! mix!the!cement!at!room!temperature,!in!a!bowl,!for!30!s,!according!to!the!cement! manufacturer’s! instructions.! The! cement! dough! was! then! transferred! into! standardKsized!moulds!for!compression!tests!on!acrylic!bone!cements!for!TJRs! (ASTM!2008),!with!the!nominal!dimensions!of!the!specimen!being!!6!mm!in! diameter!and!12!mm!in!height.!The!specimens!were!cured!at!room!temperature! and!then!pushed!out!of!the!moulds!with!a!plunger.! QuasiKstatic! compression! testing! was! performed! using! a! universal! materials! testing! machine! (AGSKX,! Shimadzu,! Kyoto,! Japan),! in! order! to! determine! the! stress!at!zero!cycles.!The!tests!were!performed!according!to!ASTM!FK451!(ASTM! 2008)!on!11!specimens.!! The! specimens! intended! for! fatigue! testing! were! examined! visually! and! radiographically! (Faxitron®! HP! Cabinet! XKray! System,! Faxitron! Bioptics! LLC,! Tucson,!AZ,!USA)!for!defects,!with!specimens!containing!pores!with!diameter! larger!than!1!mm!being!rejected!(Cristofolini!et!al.!2000).!The!rejection!rate,!i.e.,! the! number! of! discarded! specimens! as! a! proportion! of! the! total! number! of! manufactured!specimens,!(46%)!was!within!the!range!previously!reported!(40!–! 60%)!(Lewis!2000;!Boelen!et!al.!2008;!Lewis!et!al.!2009a).! The! fatigue! tests! were! performed! under! ambient! conditions! in! a! dynamic! material!testing!system!(MTS®!Axial!858!Mini!Bionix®II,!MTS!Systems!Corp.,! Eden!Prairie,!MN,!USA).!Each!of!the!accepted!specimens!was!subjected!to!a!small! preKload! of! 20! N,! followed! by! a! constantKamplitude! cyclic! compressionK compression!load,!at!a!frequency!of!2!or!10!Hz.!A!frequency!of!2!Hz!is!the! prescribed,! clinically! relevant,! frequency! in! the! standard! (ASTM! 2009);! a! frequency!of!10!Hz,!on!the!other!hand,!was!merely!used!in!order!to!investigate!a! possible!acceleration!of!the!test.!The!applied!compressive!loads!corresponded!to! maximum!stress!levels!of!50.0,!55.0,!60.0,!62.5!and!75.5!MPa!at!the!lower!tested! frequency;!and!of!40.0,!55.0,!60.0,!62.5!or!75.5!MPa!at!the!higher!frequency.!A! stress!level!of!twoKthirds!of!the!quasiKstatic!compression!strength!was!chosen!as! the! starting! point! and! steps! of! 2.5! MPa! were! used! to! identify! the! relevant! stresses! (Little! 1975;! Lewis! et! al.! 2009a).! For! each! specimen,! the! load! was! ! 6! ramped!up!in!a!tapered!sinusoidal!manner!during!the!first!20!cycles!until!the! maximum! load! was! reached.! RunKout! was! taken! to! be! 5! million! cycles,! as! indicated! by! the! standard! for! tensionKcompression! testing! of! acrylic! bone! cements!(ASTM!2009).!Since!failure!could!not!be!detected!as!a!sudden!decrease! in!load!in!all!cases!(at!lower!applied!load,!the!specimen!continued!to!deform!over! time!but!not!in!a!catastrophic!manner),!failure!was!taken!to!occur!at!a!nominal! strain!(calculated!during!testing!from!the!load!frame!displacement)!value!of! 15%,! as! vertebral! compression! fractures! are! detected! at! a! vertebral! height! reduction!of!15!–!25%!(Schwartz!and!Steinberg!2005).!Four!specimens!were! tested!at!each!combination!of!stress!and!frequency!level,!with!the!following! exceptions!for!which!three!specimens!were!tested:!50.0!MPa!and!2!Hz;!62.5!MPa! and!2!Hz!;!62.5!MPa!and!10!Hz.!Additional!fatigue!data!come!from!preliminary! tests,!with!only!one!tested!specimen!at!each!stress!level.! The!test!results!were!analyzed!using!the!Olgive!equation!(Krause!et!al.!1988):! !!! ! = !+ ,! (1)! ! !"#!! !! ! where#S!is!the!applied!stress!(in!MPa),!N!is!the!number!of!cycles!to!failure,!and!A,! f B,!C!and!D!are!material!constants.!A!corresponds!to!the!lower!asymptote!of!the! curve!(estimated!fatigue!limit),!B!is!upper!asymptote,!C!is!the!number!of!cycles!at! the!inflection!point!of!the!curve,!and!D!is!related!to!the!slope!at!the!inflection! point! (Krause! et! al.! 1988).! The! LevenbergKMarquardt! nonKlinear! regression! method,!available!in!the!Curve!Fitting!Toolbox™!in!MATLAB®!(Version!R2012a,! The!MathWorks®!Inc.,!Natick,!MA,!USA)!was!used!to!estimate!the!values!of!the! material! constants!in!Eq.!(1).! IBM®! SPSS®! Statistics! (Version! 19,! IBM! Corp.,! Armonk,!NY,!USA)!was!used!to!make!a!statistical!comparison!of!the!log!fatigue! life!at!the!two!frequencies,!using!a!tKtest!at!each!stress!level! (ASTM!2009).! ShapiroKWilk’s!test!was!first!used!to!confirm!normality!of!the!data.! At!each!combination!of!applied!stress!and!frequency,!a!twoKterm!power!function! was!used!to!analyze!the!cumulative!nominal!strain!(up!to!a!maximum!strain!of! 15%)KversusKnumber!of!stress!cycles,!N!(Curve!Fitting!Toolbox™!in!MATLAB®,! Version!R2012a,!The!MathWorks®!Inc.,!Natick,!MA,!USA).!This!function!was!! ! 7! ! = !!! +!,! (2)! where!a,!b,!and!c!are!constants.!Results!from!these!analyses!were!used!to!identify! cement!failure!modes.! ! 3. Results*and*discussion* The!quasiKstatic!compressive!strength!of!Osteopal®V!was!found!to!be!87.8!±!2.8! MPa,!which!serves!as!the!stress!level!at!zero!cycles!in!Fig.!1.!This!result!is!similar! to!the!previously!reported!strength!(97.5!±!8.7!MPa)!of!handKmixed!Osteopal®! (Lewis!2000),!a!similar!formulation!to!Osteopal®V!but!with!lower!amount!of! radiopacifier!(6!wt%!of!powder!instead!of!45!wt%).! The!S1N!results!and!the!Olgive!equation![Eq.!(1)]!fit!to!these!results!are!shown!in! f Fig.1,!while!the!estimated!values!of!the!Olgive!equation!parameters!are!given!in! Table!1.!The!fatigue!strengths!presented!here!(55.4!MPa!at!2!Hz)!are!lower!than! previous!findings!for!acrylic!cement!under!compression!(CMW1®);!the!fatigue! strength!was!found!to!be!71!MPa!at!2Hz!for!the!CMW1®!cement,!by!extrapolation! of!the!regression!curve!to!1!million!cycles!(Serbetci!et!al.!2004).!However,!the! cement! composition! differs! (CMW1®! is! aimed! for! prosthesis! fixation! and! contains,!e.g.,!9%!BaSO !and!higher!relative!amounts!of!activator!and!initiator)!–! 4 which! will! influence! the! molecular! structure! and! hence! the! mechanical! properties.! The! mean! fatigue! life! of! different! cement! brands! in! tensionK compression! has! in! fact! been! found! to! differ! substantially! (Lewis! 2003).! However,!the!fatigue!strengths!found!in!our!study!as!well!as!the!one!on!CMW1®,! are!substantially!higher!than!those!found!for!acrylic!bone!cements!tested!at!2!Hz! in!fully!reversed!tensionKcompression!fatigue,!both!those!developed!for!fixation! of!TJR’s!as!well!as!those!developed!for!VP.!In!fact,!mean!fatigue!limits!of!8.1!–! 13.1!MPa!(Lewis!and!Austin!1994;!Lewis!and!Mladsi!1998;!Lewis!2000))!have! been!found!for!cements!used!in!TJR’s!and!mean!fatigue!limits!of!6.8!–!10.4!MPa! (95%!confidence!bounds!2.8!–!12.8!MPa)!(Boelen!et!al.!2008;!Lewis!et!al.!2009a)! for!cements!developed!for!VP.!In!particular,!the!estimated!fatigue!limit!at!2!Hz!of! a!similar!cement!to!Osteopal®V!was!found!to!be!11.0!MPa,!when!tested!in!a!fully! reversed!tensionKcompression!fatigue!test!(Lewis!2000).!Osteopal®!(the!cement! ! 8! used!in!the!aforementioned!study)!has!a!lower!amount!of!ZrO !compared!to! 2 Osteopal®V,!but!is!from!the!same!cement!brand!and!contains!the!same!chemical! components.!Unfortunately,!there!are!no!data!available!comparing!the!fatigue! strengths!of!commercial!cements!from!the!same!producer!containing!different! amounts! of! radiopacifier.! One! study! (Kurtz! et! al.! 2005),! performed! under! tensionKcompression!fatigue,!on!different!cements!containing!10,!30!and!36!wt%! BaSO !found!that!the!cement!containing!30!wt%!BaSO !gave!somewhat!better! 4 4 fatigue! properties! than! the! cement! containing! 10! wt%,! while! the! cement! containing! 36! wt%! performed! worse! than! both! of! the! other! formulations.! However,! while! the! cements! containing! 10! and! 30! wt%! BaSO ! were! both! 4 commercial!formulations,!they!came!from!different!brands!(the!formulations! were! Simplex®P! and! KyphX! HVKR,! respectively).! Furthermore,! the! cement! containing!36!wt%!BaSO !was!an!experimental!formulation,!based!on!Simplex®P,! 4 and!it!was!hypothesized!that!agglomeration!together!with!a!less!homogenous! distribution!of!the!radiopacifier!in!the!cement!affected!the!properties!negatively.! Hence,!the!effect!of!the!amount!of!radiopacifier!on!the!mechanical!properties!of! acrylic!bone!cement!remains!inconclusive,!although!it!is!unlikely!that!the!effect!is! as!large!as!the!difference!found!here!in!fatigue!properties!between!cements! tested! under! tensionKcompression! and! compressionKcompression.! Although! there!are!no!data!on!the!performance!of!the!exact!same!cement!composition!in! fully!reversed!tensionKcompression!fatigue,!the!much!higher!estimated!fatigue! limit! found! in! this! study! compared! to! the! previously! published! data,! could! indicate! that! tensionKcompression! fatigue! testing! may! substantially! underestimate! the! performance! of! cements! intended! for! vertebroplasty.! Moreover,!as!previously!mentioned,!Gates!et#al.!(Gates!et!al.!1983)!found!that!the! effect! of! compression! appeared! negligible! during! fully! reversed! testing! by! comparing!cyclic!zeroKtension!loading!to!tensionKcompression.! The!fatigue!limits!presented!here!are!substantially!higher!than!stresses!typically! experienced! by! vertebral! bodies! during! many! normal! daily! activities! (for! example,!at!L4KL5,!stress!ranges!from!0.1!MPa,!while!lying!supine,!to!2.3!MPa,! while!lifting!20!kg,!bent!over!with!round!back!(Wilke!et!al.!1999)).!Furthermore,! mechanical!testing!of!human!vertebral!trabecular!bone,!in!the!thoracicKlumbar! ! 9!