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Annals of Biomedical Engineering, Vol. 32, No. 1, January 2004 (© 2004) pp. 77–91 Evolution of Vertebroplasty: A Biomechanical Perspective KAY SUN and MICHAEL A. K. LIEBSCHNER Department of Bioengineering, Rice University, TX (Received 3 June 2003; accepted 23 September 2003) Abstract—This paper is a collection of computational, finite ele- ment studies on vertebroplasty performed in our laboratory, which attempts to provide new biomechanical evidence and a fresh per- spective into how the procedure can be implemented more effec- tively toward the goal of preventing osteoporosis-related fractures. The percutaneous application of a bone cement to vertebral de- fects associated with osteoporotic vertebral compression fracture has proven clinical successful in alleviating back pain. When the biomechanical efficacy of the procedure was examined, however, vertebroplasty was found to be limited in its ability to provide suf- ficient augmentation to prevent further fractures without risking complications arising from cement extravasations. The procedure may instead be more efficient biomechanically as a prophylac- tic treatment, to mechanically reinforce osteoporotic vertebrae at risk for fracture. Patient selection for such intervention may be reliably achieved with the more accurate fracture risk assess- ments based on vertebral strength, predicted using geometrically detailed, specimen-specific finite element models, rather than on bone density alone. Optimal cement volume, placement, and ma- terial properties were also recommended. The future of vertebro- plasty involving biodegradable augmentation material laced with osteogenic agents that upon release will stimulate new bone growth and increase bone mass was proposed. Keywords—Spine biomechanics, Finite element modeling, Frac- ture repair, Prophylactic vertebroplasty, Vertebral reinforcement, Bone cement. INTRODUCTION Vertebroplasty was pioneered in France in 1984 by Galibert and colleagues, 27 and it involves the percutaneous application of an acrylic bone cement, poly(methylmethacrylate) (PMMA) to vertebral defects (Fig. 1). This procedure was first used to treat aggres- sive vertebral hemangioma and resulted in good pain relief. In 1991, Debussche-Depriester et al. 22 focused the treat- ment on osteoporotic compression fractures and also ex- perienced success in pain control. Indications were sub- sequently extended to other weakening lesions, such as vertebral myeloma and metastatic vertebral lesions. Since its introduction to the United States in 1993, the focus has Address correspondence to Michael A.K. Liebschner, PhD, Depart- ment of Bioengineering, MS-142, Rice University, 6100 Main Street, Houston, TX 77005. Electronic mail: [email protected] remained on the relief of pain associated with osteoporotic vertebral fractures that have failed to respond to conserva- tive therapy. 37,52 Although there have been no prospective, randomized, controlled studies comparing vertebroplasty with standard medical therapy, the clinical studies demon- strated high rates of rapid pain relief 3,7,17,20,30,39,50,63 and increase in mobility. 3,17,39,65 The hardening of the injected cement is believed to inhibit painful micromotion at the fracture site, thereby stabilizing the microfractures. 8,9,25,59 Vertebroplasty has also been suggested for use as a fracture prevention treatment by providing immediate mechanical reinforcement to the fragile osteoporotic vertebrae at-risk for fractures. The objective of vertebroplasty mechanically is to re- store the structural properties of the weakened vertebrae to “normal” levels, so that the weight-bearing kinetics during regular daily activities is sufficiently supported. By inves- tigating the biomechanics of vertebroplasty with restora- tion of vertebral properties as the main motivation, treat- ment procedure, in terms of the volume, placement, and material properties of the injected bone cement, can be re- fined and optimized. Specimen-specific and anatomically detailed finite element models of human vertebral bod- ies, which had been calibrated to experimental results of the same specimens, were used to simulate vertebroplasty using various treatment procedures. The recommended procedure will serve to improve the effectiveness of the treatment biomechanically, in hopes of preventing further fractures. BIOMECHANICAL GOAL OF VERTEBROPLASTY Successful repair of the collapsed vertebrae was con- sidered to have been achieved when strength is restored to prefractured values. 10 By increasing vertebral strengths to prefracture levels, additional fractures could, theoreti- cally, be prevented if the spine were loaded to the same magnitude that caused the initial fracture. Unfortunately, since 58% of osteoporotic vertebral fractures occur spon- taneously during routine activities, 15 the loads experienced in subsequent fractures will easily equal or exceed that of the initial collapse. Consequently, the fractured vertebrae 77 0000-6964/04/0100-0077/1 C 2004 Biomedical Engineering Society

Evolution of Vertebroplasty: A Biomechanical Perspective

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Annals of Biomedical Engineering [AMBE] PP1058-ambe-477012 December 8, 2003 20:11 Style file version 14 Oct, 2003

Annals of Biomedical Engineering, Vol. 32, No. 1, January 2004 (© 2004) pp. 77–91

Evolution of Vertebroplasty: A Biomechanical Perspective

KAY SUN and MICHAEL A. K. L IEBSCHNER

Department of Bioengineering, Rice University, TX

(Received 3 June 2003; accepted 23 September 2003)

Abstract—This paper is a collection of computational, finite ele-ment studies on vertebroplasty performed in our laboratory, whichattempts to provide new biomechanical evidence and a fresh per-spective into how the procedure can be implemented more effec-tively toward the goal of preventing osteoporosis-related fractures.The percutaneous application of a bone cement to vertebral de-fects associated with osteoporotic vertebral compression fracturehas proven clinical successful in alleviating back pain. When thebiomechanical efficacy of the procedure was examined, however,vertebroplasty was found to be limited in its ability to provide suf-ficient augmentation to prevent further fractures without riskingcomplications arising from cement extravasations. The proceduremay instead be more efficient biomechanically as a prophylac-tic treatment, to mechanically reinforce osteoporotic vertebraeat risk for fracture. Patient selection for such intervention maybe reliably achieved with the more accurate fracture risk assess-ments based on vertebral strength, predicted using geometricallydetailed, specimen-specific finite element models, rather than onbone density alone. Optimal cement volume, placement, and ma-terial properties were also recommended. The future of vertebro-plasty involving biodegradable augmentation material laced withosteogenic agents that upon release will stimulate new bone growthand increase bone mass was proposed.

Keywords—Spine biomechanics, Finite element modeling, Frac-ture repair, Prophylactic vertebroplasty, Vertebral reinforcement,Bone cement.

INTRODUCTION

Vertebroplasty was pioneered in France in 1984by Galibert and colleagues,27 and it involves thepercutaneous application of an acrylic bone cement,poly(methylmethacrylate) (PMMA) to vertebral defects(Fig. 1). This procedure was first used to treat aggres-sive vertebral hemangioma and resulted in good pain relief.In 1991, Debussche-Depriesteret al.22 focused the treat-ment on osteoporotic compression fractures and also ex-perienced success in pain control. Indications were sub-sequently extended to other weakening lesions, such asvertebral myeloma and metastatic vertebral lesions. Sinceits introduction to the United States in 1993, the focus has

Address correspondence to Michael A.K. Liebschner, PhD, Depart-ment of Bioengineering, MS-142, Rice University, 6100 Main Street,Houston, TX 77005. Electronic mail: [email protected]

remained on the relief of pain associated with osteoporoticvertebral fractures that have failed to respond to conserva-tive therapy.37,52 Although there have been no prospective,randomized, controlled studies comparing vertebroplastywith standard medical therapy, the clinical studies demon-strated high rates of rapid pain relief3,7,17,20,30,39,50,63 andincrease in mobility.3,17,39,65 The hardening of the injectedcement is believed to inhibit painful micromotion at thefracture site, thereby stabilizing the microfractures.8,9,25,59

Vertebroplasty has also been suggested for use as a fractureprevention treatment by providing immediate mechanicalreinforcement to the fragile osteoporotic vertebrae at-riskfor fractures.

The objective of vertebroplasty mechanically is to re-store the structural properties of the weakened vertebrae to“normal” levels, so that the weight-bearing kinetics duringregular daily activities is sufficiently supported. By inves-tigating the biomechanics of vertebroplasty with restora-tion of vertebral properties as the main motivation, treat-ment procedure, in terms of the volume, placement, andmaterial properties of the injected bone cement, can be re-fined and optimized. Specimen-specific and anatomicallydetailed finite element models of human vertebral bod-ies, which had been calibrated to experimental results ofthe same specimens, were used to simulate vertebroplastyusing various treatment procedures. The recommendedprocedure will serve to improve the effectiveness of thetreatment biomechanically, in hopes of preventing furtherfractures.

BIOMECHANICAL GOAL OF VERTEBROPLASTY

Successful repair of the collapsed vertebrae was con-sidered to have been achieved when strength is restoredto prefractured values.10 By increasing vertebral strengthsto prefracture levels, additional fractures could, theoreti-cally, be prevented if the spine were loaded to the samemagnitude that caused the initial fracture. Unfortunately,since 58% of osteoporotic vertebral fractures occur spon-taneously during routine activities,15 the loads experiencedin subsequent fractures will easily equal or exceed that ofthe initial collapse. Consequently, the fractured vertebrae

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78 K. SUN and M. A. K. LIEBSCHNER

FIGURE 1. Illustration of vertebroplasty. (a) Collapsed vertebral fracture (b) The bone biopsy needle penetrates the pedicle andenters the body of the vertebra that has a compression fracture. (b) The PMMA fills the vertebra.

need to be strengthened to “normal” or low fracture risklevels that enable sufficient support of the weight-bearingkinetics.59

Bone density has been adopted as the most commontechnique for vertebral fracture risk assessment, but recentstudies have reported a substantial overlap in bone densitymeasurements of individuals with and without osteoporoticfractures,1,28,31,54 demonstrating a low sensitivity of the cri-teria. A stronger basis for fracture risk may be with vertebralstrength since risk of fracture is a measure of the probabil-ity of a mechanical overload in bone. Vertebral strengthpredictions had been shown to be of significantly higher ac-curacy if, in addition to bone density, geometry of the bonespecifically endplate area was also accounted for (r = 0.80,standard error of estimate= 1.06 kN), compared to withbone density alone (r = 0.62, standard error of estimate=1.40 kN).14 The compressive strength of lumbar vertebraewas estimated using a regression formula determined bycorrelating the strengths of the spinal segments mechani-cally tested under uniaxial compression against bone den-sity and endplate area obtained from quantitative computedtomography (QCT) scans.14

Strength (kN)= 0.32+ 0.00308× density (mg/cm3)

× endplate area (cm2) (1)

Biggemannet al.13 later used this formula to quantifythe “normal” vertebral strength values needed to sustainspinal load during regular daily activities. The L3 vertebralstrength of 75 patients (53 females and 22 males) were es-timated from the regression and related to the risk of verte-bral fracture determined from the percentage of spines withat least one fractured vertebra between T10 and L5. Twoclearly defined strength groups were noted: 100% fracturerisk for strengths less than 3 kN (high risk) and 0% risk forstrengths greater than 5 kN (low risk). Strengths between3 and 5 kN were at an intermediate risk group. As such,the “normal” or low fracture risk level for the L3 vertebrais when its compressive strength is at least 5 kN. By nor-malizing the strength levels by total endplate area, the samedefinitions could be applied to other vertebral levels.

The absence of posterior elements in the human vertebralbodies used in the subsequent studies had to be corrected forby accounting for the 26% load-bearing contribution of thefacets under axial compression when still attached withinthe continuum of a spinal segment.4,64 The adjusted defi-nition of the three fracture risk groups are high-risk group(fracture risk of 100%) with ultimate stress less than 1.6MPa, medium risk group with ultimate stress from 1.6 to2.7 MPa, and low-risk group (fracture risk near 0%) withultimate stress greater than 2.7 MPa. Therefore, the biome-chanical goal of vertebroplasty should be to increase themaximum sustainable compressive stress of the vertebralbody to a level beyond low fracture risk (>2.7 MPa) so asto prevent further fractures.

FINITE ELEMENT MODELING

A full investigation of the success of vertebroplasty in at-taining the biomechanical goal would traditionally requirein vitro mechanical testing of cadaveric specimens. How-ever, because of the many parameters affecting the biome-chanical effectiveness of the treatment, namely volume,placement, and material properties of the injected bone ce-ment, as well as the initial bone density of the vertebraand the severity of the fracture in the case of fracture re-pair, an unrealistically large number of specimens wouldbe needed to demonstrate a statistical distinction in me-chanical enhancements with one variable over another foreach of the five parameters. The large number of samplesrequired is due to biological variability in the cadavericspecimens, which can be eliminated using computationalapproach since multiple analyses can be repeated on thesame specimen. Another benefit of computer modeling isin the simulation of vertebroplasty, where the volume anddistribution of the bone cements can be controlled in anexact and precise manner not possible in cadaveric studies.This feature enabled any discrepancies in mechanical en-hancements to be attributed solely on the parameter beinginvestigated. As a result, the total number of variables thatactually needed to be studiedin vitro can be significantly

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Vertebroplasty Evolution 79

reduced with computer modeling, leaving only the optimalparameters for verification with cadaveric testing.

Geometrically accurate, specimen-specific, three-dimensional computer-simulated finite element model ofeach human vertebral body were generated by first takingQCT scans of the specimen. Radiographically normal,whole vertebral bodies obtained from cadaver donors hadtheir posterior elements removed using an autopsy saw andintervertebral disc material dissected from both endplatesusing scalpels. Eighteen to twenty-four QCT scans of1.5 mm thick transverse cross-sections were obtainedfor the vertebral body using a clinical scanner (GE9800,General Electric, Milwaukee, WI). During scanning, thevertebral body was held in place using an acrylic fixtureand submerged in water in a container of about the samesize as the human torso in order to mimic the human body.A liquid K2HPO4 phantom (Mindways Software, Inc., SanFrancisco, CA) was included in each scan to correct forscanner drift and to convert CT numbers in Hounsfieldunits to bone mineral density in gram per centimeterscube.43.

A custom-written contouring algorithm was used to ex-tract the bone geometry from the QCT scans, and then bystacking these images, a three-dimensional geometry of thevertebral body was reconstructed (TrueGrid, XYZ Scien-tific Applications Inc., Livermore, CA).44 The trabeculartissue of the vertebral body interior was paved with 20-noded brick elements and each trabecular element was as-signed an elastic modulus in the superior to inferior direc-tion (Ezz) based on the following relation.41

Ezz(MPa)= 3850ρQCT(g/cm3)− 81.9

r 2 = 0.76, n = 76 (2)

whereρQCT is the QCT mineral densities. The other elas-tic constants (Young’s modulus: Exx, Eyy; Poisson’s ratio:νxy, νxz, νyz; Shear modulus:Gxy, Gxz, Gyz) were de-rived from ratios obtained by Ulrichet al.60 The plasticmaterial definitions of the trabecular elements were basedon postyield trabecular tissue properties determined fromfive points defined along the normalized (stress divided bymodulus) stress–strain curve measured empirically from 22cylindrical vertebral trabecular cores loaded to failure undercompression in the longitudinal direction (z-direction).42Asno data was currently available on the nonlinear compres-sive behavior of vertebral bone in the transverse direction,the same postyield properties were assumed for all three di-rections, however normalized by the directional modulus.The assigned postyield trabecular tissue properties werepreviously proven successful in accurately predicting ul-timate vertebral fracture load.46 In addition, the modelsshowed an insensitivity to variations in material proper-ties in the transverse direction for the loading conditionsapplied.44

The cortical shell and endplates were assumed to havea nominal thickness of 0.35 mm.58 The shell was alsopaved with 20-noded brick elements, and was assumed tobe isotropic, with Poisson’s ratio of 0.362 and ultimate strainof 1.4%.41 Since there is no correlation between the elasticmodulus of the cortical shell and vertebral stiffness,44 theshell modulus of the vertebral body was determined throughcalibration. The calibration process involved varying theshell modulus until the simulated structural stiffness calcu-lated matched the stiffness determined from experimentalloading.44

To prepare the vertebral bodies for mechanical testing,poly(methylmethacrylate) (PMMA) was molded to the con-cave endplates of the vertebral body using a fixture thatensured planoparallel ends (see Kopperdahlet al.43 for de-tails). Compression tests of the vertebral bodies were per-formed between steel platens on a screw-driven load frame(Instron Corporation, Model 5583, Canton, MA). The up-per platen was attached to a ball joint, which was lockedin place after applying a preload of 50 N. Each vertebralbody was then preconditioned by cycling five times be-tween 200 and 400 N and held for five min at 300 N, inorder to reduce visoelastic effects and allow proper seat-ing between the platens, PMMA, and vertebral endplates.43

After preconditioning, the specimen was loaded monotoni-cally in displacement control at a rate of 0.15 mm/s (∼0.5%strain per second) to a randomly selected strain level. Strainswere based on the initial height of each specimen, includ-ing PMMA, measured using calipers, and recorded using a2-in. extensometer spanning the platens. From the load de-formation curve recorded, the vertebral stiffness and frac-ture strength derived were used in calibration and verifica-tion of the finite element model, respectively.

A further addition to the model was PMMA, with a mod-ulus of 2500 MPa and Poison’s ratio of 0.3, added at bothendplates of the vertebral body model in order to simu-late the parallel loading surfaces in the experimental testconditions.43 The final mesh was verified and adjusted soas to prevent element distortion.44 All finite element analy-ses were performed using commercially available software,ABAQUS version 5.8 (Hibbit, Karlsson and Sorenson, Inc.,Pawtucket, RI). Finite element models of vertebral bod-ies generated with this procedure were highly accurate.The predicted compressive behavior of the vertebral bodiesclosely matched the experimentally determined behaviorand the predicted fracture loads were strongly correlatedwith the measured values (n= 9, r 2= 0.94, p< 0.0001,average absolute error of 12.0%).46

Since the finite element modeling technique employedgenerated accurate virtual replications of the actual ver-tebral bodies, the results produced from the models weredeemed plausible and realistic. The models were de-veloped based on QCT scans of the vertebral bodies,thereby incorporating the specific geometry and bone den-sity distribution of each specimen. By defining the material

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80 K. SUN and M. A. K. LIEBSCHNER

property of each trabecular element in the finite elementmodels based on the corresponding pixel value derived fromthe QCT scans, the exactly heterogeneity within the verte-bral body was duplicated. Furthermore, the vertebral bod-ies were modeled using anisotropic elastic constants. Sincebone is an orthotropic material with strong dependency oftrabecular bone material properties on both mineral den-sity and orientation,29 a more accurate model of bone be-havior would be achieved if anisotropic material proper-ties were used. Finally, the specimen-specific finite elementmodels were calibrated so that the predicted vertebral stiff-ness corresponded to the experimentally determined values.This procedure provided more accurate postyield predic-tions compared to other models that determined the corti-cal bone material properties from elastic modulus-densityrelationships.26,35,57

BIOMECHANICAL EFFICACY OFVERTEBROPLASTY FOR REPAIR AND

REINFORCEMENT

Using finite element models and the biomechanical goalof improving vertebral strength to low fracture risk levelsas the success criterion, the biomechanical efficacy of theprocedure for the two treatment scenarios, fracture repairand vertebral reinforcement, were compared. Since this wasa comparison study of the effect of PMMA volume on ver-tebral augmentation between the repair and reinforcement,only the initial mechanical properties of the damaged andundamaged vertebrae will differ, while all other factors,such as bone density, geometry and cement placement andvolume, must remain identical in order to credit the successof the treatment on its efficacy. As such, only one verte-bral body specimen selected from a population at-risk forosteoporotic fractures was required.

A L1 vertebral body, with an average QCT densityof 0.0743 g/cm3, obtained from a 73-year-old female ca-daver was used in this study. The intact vertebral bodyhad an experimentally determined compressive stiffnessof 8243 N/mm and fracture strength of 3.02 kN (ultimatestress= 2.02 MPa), which placed it in the medium risk offracture. The predicted compressive behavior of the intactvertebral body closely matched the behavior obtained frommechanical testing, with an error of−7.54% in fractureload prediction. The vertebral body was loaded again in or-der to determine the mechanical properties of the fracturedvertebral body, which were used to verify the accuracy ofthe damage vertebral body model. In the first loading cycle,after the ultimate point was exceeded, the specimen was un-loaded and held for 1 min with a compressive force of 100N. The specimen was subsequently reloaded to 10% strain.The damage mechanically created in the vertebral body re-sulted in a 49.7% reduction in stiffness to 4150 N/mm anda 27.9% reduction in fracture strength to 2.18 kN (ultimate

stress= 1.71 MPa), still within the medium fracture risklevels.

To replicate damage in the vertebral body computermodel, the model was initially loaded under a simulateduniaxial compression to beyond the ultimate point by apply-ing a uniform compressive displacement to the top layer ofPMMA at the superior endplate of the vertebral body modelin order to duplicate experimental loading conditions. Ver-tebral stiffness and strength reductions corresponding tothose determined experimentally were modeled by respec-tively lowering the elastic modulus and ultimate strength ofall trabecular elements based on the total strains experiencedby each element during the simulated loading cycle.40

%1E = 277ε

ε + 6.18, r 2 = 0.92, n = 40 (3)

%1S= 3.76ε2+ 3.87ε, r 2 = 0.45, n = 25 (4)

where %1E and %1Sare the percent modulus and strengthreduction in each element after the initial loading cycle asa function of percent total strain (ε) applied in the verticalaxis. The maximum percent reduction was limited to 85%for elastic modulus and 45% for strength.40 Damage to thecortical bone was simulated by reducing the elastic modu-lus of the cortical elements that had exceeded its yield pointto the secant modulus (perfect damage modulus), wherethe final stress reached became the new yield stress. Thiscorrelation suggested that damage is a primary mechanismfor the modulus reduction rather than plastic deformation.19

After simulating damage, a uniform compressive displace-ment was applied to the model to determine the stiffnessand strength of the damaged vertebral body. The stiffnessand fracture strength of the damaged vertebral body werewell predicted with errors of−18.7 and 8.27%, respectively(Table 1).

Bipedicular vertebroplasty (Fig. 2(a)) was simulated inboth the damaged and undamaged specimen-specific ver-tebral body models by replacing elements with trabecu-lar bone properties with PMMA properties. Four differentPMMA volumes (2.5, 3.5, 5, and 7.5 cm3) correspondingto 10, 15, 20, and 30% volume fill to the whole vertebralbody volume were used. The plastic material definitionsof PMMA were derived from six points specified alongthe postyield compressive behavior of the bone cement.51

ABAQUS was used to simulate uniaxial compression soas to predict the stiffness and fracture load of the treatedand untreated vertebral body models for both repair andreinforcement.

When the effect of PMMA bone cement volume on verte-bral compressive strength enhancements for both treatmentscenarios of repair and reinforcement were examined, wefound that 30% volume fill of PMMA was needed to im-prove vertebral strength to low fracture risk levels for frac-ture repair, compared to only half of that for reinforcement(Fig. 3). The required volume for repair was 43% higher

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TABLE 1. Experimentally determined and computer predicted mechanical properties of an intact and damaged vertebral body withan average QCT density of 0.0743 g/cm 3.

Intact Damaged Reduction in Properties

Experimental Predicted Error (%) Experimental Predicted Error (%) Experimental (%) Predicted (%)

Stiffness (N/mm) 8243 8243 0 4150 3375 −18.7 49.7 59.1Fracture strength (kN) 3.02 2.79 −7.54 2.18 2.36 8.27 27.9 15.6Ultimate stress (MPa) 2.19 2.02 −7.54 1.58 1.71 8.27 27.9 15.6

than the typical volumes used clinically in vertebroplasty(20% fill). Of all the reported patients who underwentvertebroplasty for fracture repair, 30–67% experiencedcement leakages outside the vertebral body,48 and into theperivertebral or epidural veins, soft tissue around the spine,epidural space, or along the needle track, and interverte-bral disc.24 Although reported complication rates are low,ranging from 1 to 10%,38 such leakage could result in com-pression of the spinal cord and nerve roots, as well as pul-monary embolism.16,18,23,50 Therefore, the cement volumeneeded to achieve the biomechanical goal for fracture repairis high enough to pose a significant risk of cement leakageand further complications.

The cement volume recommended for fracture repairby the finite element analyses coincided with the resultsfrom previousin vitro biomechanical studies by Belkoffet al.8,10,11 In those cadaveric studies, the stiffness andstrength augmentations of fractured vertebrae injected withvarious types of bone cement at different volumes were in-vestigated. Damaged was mechanically created to the singlevertebral bodies, which also had their posterior elementsremoved, by applying a uniaxial compressive force untilfailure or when 25% height reduction was reached. Afterrepair with vertebroplasty, the treated vertebrae were againmechanically tested under uniaxial compression. For thebone cement PMMA (Simplex P), thein vitro tests showedultimate lumbar vertebral stress increased to low fracturerisk levels (>2.7 MPa) when 6–8 cm3 of cement were in-troduced, corresponding to 23–31% volume fill. There wasalso a three times higher incidence of extravasations re-ported in the 8 ml (31%) fill group compared to the 6 ml(23%) fill group, while none was observed for volume fillsless than 4 ml (15.5%).10 The results from thein vitro ver-

FIGURE 2. Finite-element mesh of a vertebral body with (a) two PMMA capsules (shaded) simulating bipedicular vertebroplasty(left) and (b) one PMMA capsule in the horizontal plane simulating posterolateral vertebroplasty (right). 45

tebroplasty studies substantiated the findings of the presentfinite element study by corroborating the 30% fill of PMMAneeded for fracture repair along with the heightened risk ofextravasations with such a large cement volume. As such,vertebroplasty may be biomechanically more effective forvertebral reinforcement than for repair.

BIOMECHANICS OF PROPHYLACTICVERTEBROPLASTY

Immediate strength enhancements can be achieved uponhardening of the injected cement.5,8−11,21,33,34,36,47,56,59

This feature of vertebroplasty makes it an extremely effec-tive prophylaxis for fractures. However, more refinementsare still required to make the procedure safer. The high inci-dence of cement leakage can be attributed to overly aggres-sive filling of the vertebral body. Therefore, to minimizethe risk of complications for prophylactic vertebroplasty,the least amount of bone cement required to improve ver-tebral strength from high to low fracture risk levels mustbe determined. This knowledge requires an understandingof all the factors that affect vertebral reinforcement, whichinclude bone cement volume, placement, and material prop-erties as well as the initial bone properties of the vertebralbody.

Refinement of Vertebroplasty Procedure

Finite element models of eight whole vertebral bod-ies were used to investigate the biomechanical effects ofPMMA bone cement volume and placement, as well asthe initial bone density on prophylactic vertebroplasty. Themean age of the specimens (L1–L4; six females, two males)

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FIGURE 3. Comparison between the PMMA volumes needed for fracture repair and reinforcement of an nonfractured vertebral bodywith average QCT density of 0.0743 g/cm 3 in order to improve the ultimate compressive vertebral stress to low fracture risk levels.The damaged vertebral body experienced a 59.1 and 15.6% reduction in stiffness and strength, respectively. The three fracture riskgroups defined by Biggeman et al. 13: high risk group (fracture risk of 100%) with ultimate strength <1.6 MPa, medium risk groupwith ultimate strength from 1.6 to 2.7 MPa, and low risk group (fracture risk near 0%) with ultimate strength >2.7 MPa.

was 71.1± 10.7 years, with mean QCT density of 0.091±0.03 g/cm3 (Table 2). The finite element models generatedsuccessfully predicted the nonlinear compressive behaviorof human vertebral bodies The predicted vertebral fractureloads deviated from the experimentally measured values byan average of 12.7% and they are strongly correlated atr 2= 0.94.

Six different PMMA volumes (1, 2.5, 3.5, 5, 7.5, and9 cm3), corresponding to 5, 10, 15, 20, 30, and 35% volumefill, were virtually implanted into each of the experimentallycalibrated vertebral body finite element models, via bipedic-ular or posterolateral vertebroplasty approaches (Fig. 2(a)and (b)). Liebschneret al.45 had previously demonstratedthat vertebral body instability might occur due to asym-metric cement placement, in the form of a medial–lateral

TABLE 2. Physical and mechanical data on all eight single vertebral bodies tested.

Specimen Donor Spine Average (SD) QCT Min/max QCT Whole VB Fracturenumber age Sex level density (g/cm3) density (g/cm3) stiffness (N/mm) strength (kN)

1 49 F L3 0.0912 (0.0132) 0.0713/0.1089 17363 6.1232 76 F L3 0.0762 (0.0157) 0.0630/0.1047 8340 2.4173 66 F L4 0.1244 (0.0173) 0.1021/0.1519 12300 4.4184 80 F L4 0.0384 (0.0069) 0.0298/0.0502 7200 2.5715 82 M L3 0.1269 (0.0268) 0.0918/0.1765 29876 9.5536 66 F L4 0.0805 (0.0150) 0.0585/0.1045 8280 2.7797 73 F L1 0.0743 (0.0178) 0.0499/0.0996 8242 2.7938 77 M L2 0.1133 (0.0227) 0.0694/0.1408 14650 6.626

Note. F for female, M for male, SD for standard deviation, VB for vertebral body.

toggle motion toward the untreated side when a compres-sive pressure load was applied. As a result, only symmetriccement placement, bipedicular and posterolateral vertebro-plasty approaches, were simulated in this study. Stiffnessand fracture load of the treated and untreated vertebral bodymodels under uniaxial compression were predicted usingABAQUS. The variations of vertebral compressive stiffnessand strength reinforcements with bone cement volumes andinitial trabecular bone densities for both approaches werescrutinized.

Vertebral stiffness and strength augmentation after vir-tual prophylactic vertebroplasty were influenced stronglyby volume fraction of the implanted cement and bone den-sity, but least affected by the distribution of PMMA. Stiff-ness and strength increases were directly proportional to

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FIGURE 4. Effect of posterolateral and bipedicular placementand volume fill of PMMA on the (a) average normalized com-pressive stiffness increase; and (b) average normalized com-pressive strength increase of reinforced vertebral bodies. Stiff-ness and strength augmentations were linearly proportional tothe PMMA volume fill for both approaches.

PMMA filler volume, with greater stiffening and strength-ening effects for the bipedicular approach versus postero-lateral for PMMA volumes higher than 20%. No significantdifferences between the two fill approaches were noted forlower cement volumes (p> 0.1; Fig. 4(a) and (b)). Greateraugmentation effects were observed for vertebral bodieswith average QCT densities below 0.1 g/cm3, with evenmore pronounced effects as the bone densities decreased.While for densities above 0.1 g/cm3, the mechanical aug-mentations were less dependent on bone density (Fig. 5(a)and 5(b)). These results agree closely with previousin vitrovertebral augmentation studies on single vertebral bodies,which were mechanically tested under uniaxial compres-sion after injection with calcium phosphate,36 PMMA orexperimental brushite cement.33 In those studies, greateraugmentation effect at lower initial bone mineral densitywas also observed.

On the basis of the results, we were able to provide fur-ther information for developing guidelines as to the min-

imum volume of PMMA bone cement needed to improvethe mechanical integrity of vertebral bodies at-risk for frac-ture to low fracture risk levels. Vertebral bodies at high riskof fracture required at least 20% volume fill of PMMA foraugmentation, while between 5–15% and 20–30% fill weresuccessful in achieving the desired strength improvementsfor vertebral bodies in the low and high spectrum of themedium risk range, respectively (Fig. 6). However, withany volume fill higher than 20%, the typical amount usedclinically, the risk of cement leakage will be greater thanthat for current vertebroplasty procedure for fracture repair.Therefore, alternative materials have to be investigated foruse on vertebral bodies at high risk of fracture. With regardsto cement placement, bipedicular vertebroplasty might bebiomechanically more efficient due to its higher strengthen-ing effect and easier surgical access than the posterolateralcase.

Adjacent Vertebrae Failure

Vertebroplasty may have the ability to prevent fracturesin the augmented vertebrae, but it also has the potentialto promote fractures in the adjacent vertebrae. As many as20% of patients with repaired vertebrae are expected to sus-tain further fractures.49,61 The majority of the new fractures(67%) are estimated to happen within just 30 days of the pro-cedure, with approximately 67% of the new fractures occur-ring in the vertebrae adjacent to the one that was treated.61

The increased risk of collapse in the neighboring vertebraeafter fracture repair has been demonstrated in both retro-spective reviews of vertebroplasty clinical studies20,30,61,65

as well asin vitro biomechanical tests.12 It has been at-tributed to the altered distribution of forces to the nearbyvertebrae caused by the shift in load or the “stress-riser”effect within the treated vertebra.59 In order to investigatethe possible “stress-riser” effect, the changes in stress andstrain distributions within a vertebral body before and aftervertebroplasty needed to be determined and finite elementmodels are ideal to study this phenomenon.

Previous studies by Baroudet al.6 and Polikeitet al.53

had investigated the effect of vertebral reinforcement withPMMA on the load transfer in the intervertebral disc withinan osteoporotic functional spinal unit using finite elementanalysis. For both models, geometric details of the spinalunits were extracted from QCT scans and homogenous ma-terial properties were assigned. Baroudet al.6 had mod-eled the lumbar segment of L4–L5 without any posteriorelements and was compressed under a step-wise displace-ment, while Polikeitet al.53 had duplicated the L2–L3 seg-ment with the facets left intact and a compressive force of1000 N under pure compression, flexion, and lateral bendingwas applied. Despite these differences, both models showedincrease in pressure within the intervertebral disc after aug-mentation with PMMA cement, which led to a large deflec-tion of the endplate into the adjacent vertebrae (12–20%).

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FIGURE 5. Effect of initial vertebral QCT density and volume fill of bone cement PMMA using bipedicular cement placement on therelative (a) compressive stiffness increase; and (b) strength increase of reinforced vertebral bodies. Greatest variations in stiffnessand strength increase for average QCT densities below 0.1 g/cm 3 and PMMA volumes over 20%. For densities greater than 0.1 g/cm 3,mechanical augmentations were less dependent on density.

Since fractures had been observed to occur preferentiallyat trabecular areas close to the endplate and at the endplateitself,36 the resultant increase in endplate deflection fromprophylactic vertebroplasty may consequently lead to frac-tures in the adjacent vertebrae. However, the models usedmay have been oversimplified as linear, isotropic, homo-geneous material properties for the trabecular bone were

assumed. As such, the stress and strain distributions be-fore and after prophylactic vertebroplasty observed in thesestudies had to be confirmed with more physiologic ma-terial distribution and properties in order to validate theirfindings.

By using our specimen-specific finite element model,with its nonuniform bone density and nonlinear, anisotropic

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FIGURE 6. Biomechanically optimal poly(methylmethacrylate) (PMMA) volume fill relative to vertebral body volume required toreduce fracture risk to low levels for bipedicular and posterolateral prophylactic vertebroplasty ( n = 8).

trabecular bone material properties, a more realistic stressand strain distribution within the treated vertebral body weredetermined. A nonfractured, osteoporotic vertebral body(L4, female cadaver of age 80 years and average QCT den-sity of 0.038 g/cm3) that had been previously generatedand calibrated to experimentally results was used to ob-serve the shift in load distribution within the vertebra afterprophylactic vertebroplasty. The stress and strain experi-enced by each element of the vertebral body, when appliedwith a simulated uniaxial compression of 2800 N (the ulti-mate load of the untreated vertebral body), before and aftertreatment with 20% volume fill or about 5 cm3 of PMMAbipedicularly were compared. ABAQUS was used in thesimulations.

Regions of high strains were found to be localized in ar-eas above and below the virtually implanted PMMA withinthe reinforced vertebral body (Fig. 7). These peaks were ab-sent for the untreated model at the same locations, althoughsharp spikes in strains were noted at the areas where thePMMA would have been implanted, which would implydamage in the unreinforced areas. This indicated that therewas a shift in the applied load toward to the stiffer PMMAregions, away from the surrounding trabecular bone. Assuch, the load was centered along the longitudinal axes ofthe injected PMMA, creating a stress concentration in theareas above and below the cement (Fig. 7). This behaviorconfirmed previous findings where the rigid PMMA cementappeared to act as an “upright pillar,”6 which amplified thestress applied in their locale. The stress concentration re-sulted in an increased intervertebral disc pressure and con-sequently, led to a significant inward bulge of the endplate ofthe adjacent vertebra.6 Thus, the chain of events stemmingfrom the shift in load distribution due to the PMMA cementmay ultimately lead to the adjacent vertebral fractures.

Prevention of such failure may be achieved by minimiz-ing the changes in load transfer mechanism after cementaugmentation. Polikeitet al.53 noticed that the effect ofprophylactic vertebroplasty on load transfer were appar-ent regardless of the volume of cement added (15–100%volume fill) as well as the placement of the material (bi-pedicular or unipedicular). Therefore, more success maybe realized through the use of softer bone cement materialsthan PMMA, in terms of stiffness, but are just as strong.

Optimal Bone Cement Material Properties

Currently, PMMA is the only available cement with re-ports of clinical application in spinal repair and reinforce-ment, though not FDA (Food and Drug Administration)approved for this procedure. The FDA issued a warning re-cently about the numerous side effects linked to the highincidence of PMMA leakage in the treatment of spinalfractures.2 These concerns, along with other PMMA short-comings, including non-biodegradability, barrier to bone re-modeling, damage to neighboring tissue because of drastictemperature increase from polymerization,25,55and possibleprovocation of fractures in the adjacent vertebrae,6,12,30,53,61

make the acrylic cement unsuitable for use in vertebroplasty,especially as a prophylactic treatment. As a result, alterna-tive bone substitutes with the desired material properties toreplace PMMA need to be investigated.

The success of the bone strengthening technique reliesheavily on the mechanical properties of the augmentationmaterial. The injected cement must have sufficient strength-ening effect to increase the strength of the augmentedvertebrae to low fracture risk levels in order to preventfuture fractures in the treated vertebrae. For the adjacentvertebrae, fracture prevention would require minimal affect

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FIGURE 7. Stress (left) and strain (right) distribution within a frontal section of an osteoporotic vertebra before and after treatmentwith 20% volume fill of PMMA (shaded).

of augmentation on load distribution. Since the premise be-hind load transfer mechanism is based on structural stiff-ness, to minimize changes in load distribution would meanvertebral stiffness augmentations must be kept to a min-imum. Therefore, the aim of vertebral reinforcement forfracture prevention is to attain maximum strength augmen-tation, while maintaining the smallest stiffness changes onthe treated vertebrae.

The biomechanically optimal bone cement materialproperties for vertebral reinforcement were determined bystudying the effects of varying cement compressive elasticmodulus and strength on the overall structural behavior ofthe treated vertebral body. Using the same eight vertebralbody models that were used previously (Table 2), bipedicu-lar vertebroplasty was simulated using 20% cement volumewith nine different material properties selected based on 1,10, 50, 100, and 150% of the elastic modulus and strength of

PMMA (Table 3). The vertebral body models were loadedunder a simulated uniaxial compression by applying a uni-form compressive displacement at the top of the model.Stiffness and fracture load of the treated and untreated mod-els were predicted using ABAQUS. The variations of verte-bral compressive stiffness and strength reinforcements withbone cement elastic modulus and strengths were scruti-nized. Optimal cement properties were determined whenthe reinforcement goal of maximum strength increase andminimum stiffness increase was reached. The degree of ver-tebral augmentations using the biomechanically determinedoptimal cement properties was also evaluated.

Strength of bone cement was noted to have no influenceon vertebral stiffness, but it did have an augmenting effecton vertebral fracture load (Fig. 8). For cement strengths be-low 5 MPa (equivalent to the strength of the surrounding tra-becular bone), the treated vertebral fracture loads fell below

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TABLE 3. The nine different bone cement material properties (M1–M9) selected forinvestigation were based on the compressive elastic modulus and strength of PMMA.

Strength (MPa)

Modulus (MPa) 1.13 (1%) 11.3 (10%) 56.5 (50%) 113 (100%) 170 (150%)

25 (1%) M6250 (10%) M71250 (50%) M82500 (100%) M1 M2 M3 M4 (PMMA) M53750 (150%) M9

that of the untreated since the bone cement was weaker thanthe trabecular bone. As the bone cement becomes strongerwith strengths rising from 5–30 MPa, the treated vertebralfracture loads were amplified to levels exceeding that of theinitial fracture load. Any increase in cement strength above30 MPa resulted in no changes in the increase in vertebralfracture loads, which remained at 47%. At that level, thebone cement was stronger than the trabecular bone, and assuch failure always occurred in the same weak area of thetrabecular bone.

Both vertebral stiffness and fracture load were affectedby the elastic modulus of the virtually implanted bone ce-ment (Fig. 9). When the bone cement modulus droppedbelow that of the surrounding trabecular bone (about300 MPa), the treated vertebral stiffness was reduced tolower than the initial stiffness. As the cement modulus roseabove 300 MPa, a gradual increase in vertebral stiffnesswas observed. This behavior was due to a shift of the loadapplied toward the stiffer cement and away from the softer

FIGURE 8. Effect of bone cement compressive strength on the average normalized compressive vertebral stiffness increase(treated stiffness/initial stiffness) and vertebral fracture load increase (treated fracture load/initial fracture load). The cement materialproperties for M1–M5 are listed in Table 3.

trabecular bone, resulting in an increase in vertebral stiff-ness. The shift in load distribution also contributed to theincrease in vertebral fracture load as the stronger bone ce-ment now bears a majority of the applied load. A maximumof 47% increase in fracture load was reached with cementmodulus greater than 1300 MPa. The plateau attained infracture load augmentation was again attributed to failurealways occurring at the same weak area of the trabecularbone.

The biomechanical goal of maximum vertebral strengthincrease with minimal vertebral stiffness augmentation wasachieved with cement modulus of 1300 MPa and strengthof at least 30 MPa. Repeating the analysis by using the op-timal cement properties (modulus= 1300 MPa, strength=30 MPa) resulted in an average increase of 40.5% in ver-tebral strength and a 45.9% average increase in vertebralstiffness at 20% volume fill, confirming our material prop-erty selection. Although cadaveric studies will still need tofollow for verification purposes, future research can now

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FIGURE 9. Effect of bone cement compressive elastic modulus on the average normalized compressive vertebral stiffness increase(treated stiffness/initial stiffness) and vertebral fracture load increase (treated fracture load/initial fracture load). The cement materialproperties for M4, M6–M9 are listed in Table 3.

be centered on injectable bone substitutes possessing theseoptimal material properties.

LONG-TERM GOAL OF VERTEBROPLASTY

The short-term goal of vertebroplasty, immediatestrength enhancement, is achieved through mechanical re-inforcement provided by the hardened injected cement. Byusing biodegradable filler materials instead of permanentones, the long-term goal of vertebroplasty, which is to re-gain bone lost to osteoporosis locally, may be attained. Webelieve that the future of vertebroplasty to lies in usage ofbioresorpable cements that offer structural support whilesimultaneously providing a temporary scaffold onto whichnew bone can grow. However, since bone requires a porousstructure to grow on, the new injectable cement will need tobe a composite of two biodegradable materials, each witha different rate of resorption. By dissolving awayin vivothe first material in the form of particles, an interconnectedporous architecture in the slower degrading primary mate-rial, which provides the main mechanical support, is gener-ated (Fig. 10). Upon degradation, the particles may also actas a drug delivery system by releasing factors such as bonemorphogenic proteins or other osteogenic factors incorpo-rated into it, thereby stimulating new bone growth. Thistissue-engineering approach aims to replace the slower re-sorbed primary material with native bone tissue. Bone massand strength will increase, lowering the risk of vertebralfracture.

The use of temporary, osteoconductive augmentationmaterial in the fight against osteoporosis is especially at-

tractive since it has the potential to slow down or even re-verse the progression of the disease, even though it is local-ized at the site of injection. Through diligent monitoring ofbone density, vertebrae at-risk of fracture can be identifiedbefore too much bone mass is lost and the biodegradablecomposite material can be injected to offer mechanical rein-forcement as well as a means to restore bone mass that hadbeen gradually lost due to the disease. The bone tissue-engineering twist added to vertebroplasty is particularlybeneficial at the time when the elderly population and lifeexpectancy are increasing, and also for juvenile osteoporoticpatients.

CONCLUSION

The strength of vertebroplasty is its simplicity and goodclinical success in terms of pain relief in the repair of frac-tured osteoporotic spine. However, it has been demonstratedthrough both finite element analyses and biomechanicalstudies of vertebroplasty that it is very challenging to re-store the biomechanical properties of fractured vertebraeto a low fracture risk levels without risking complicationsarising from cement leakages. This goal can be more effec-tively achieved by applying vertebroplasty prophylacticallyon vertebrae that have yet to fracture but are at-risk to do so.Since only half the cement volume is required to gain thesufficient augmentation to prevent further fractures for ver-tebral reinforcement compared to fracture repair, the risk ofcement extravasations and its related complications is sig-nificantly reduced. As a result, prophylactic vertebroplastymay have a higher chance of success in fracture prevention.

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FIGURE 10. Scanning Electron Micrograph (SEM) of an acrylic material embedded with Y-shaped thermoplastic polymer particlesthat had been dissolved away forming an interconnected porous architecture.

Furthermore, the surgical feasibility and safety of the pro-phylactic treatment for multilevel spinal reinforcement hasalready been demonstrated clinically.32

The caveat of prophylactic surgery is that better fractureprediction methods have to be developed to indicate whenintervention is warranted as so to ensure safe usage of theprocedure. We believe that the combination of a more accu-rate fracture risk definitions derived from vertebral strengthsrather than the conventional bone density and the use of ge-ometrically detailed specimen-specific finite element mod-els to predict vertebral bone strength may offer a reliablepatient screening criterion and a sensible rationale to un-dergo the prophylactic treatment. While automated genera-tion of patient specific finite element models is not a realityyet, the advances of software and hardware have alreadyshown a tremendous step in that direction. Moreover, sincePMMA for use in vertebroplasty has numerous adverse sideeffects,2,6,12,25,30,53,55,61 the cement may soon be replacedwith more suitable biodegradable, osteoconductive bonesubstitutes, thereby overcoming the moral dilemma trou-bled by surgeons as to whether reinforcement is justifiedand to what extent is reinforcement required. Because ofthe impermanent nature of the injected material, even if therisk of fracture had been overstated, the biodegradable ma-terial would eventually get resorbed and may be replacedwith new bone growth. The risk of an osteoporosis relatedvertebral fracture and its consequences such as pain andimmobility must be weighed carefully against the risk of

complications from the preventive treatment, which are al-ways present with any surgical procedure and can at bestbe minimized through procedural optimization and propersurgical planning. Vertebroplasty, thus, has a great potentialto serve as both an effective localized fracture preventionmeasure and treatment to increase bone mass. Further re-search would have to be conducted to explore this avenueof vertebroplasty.

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