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ARTICLE IN PRESS Medical Engineering & Physics xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
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Technical note
Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study René Aquarius a , Jasper Homminga b,∗ , Allard Jan Frederik Hosman c , Nico Verdonschot a,b , Esther Tanck a a
Radboud University Medical Center, Orthopaedic Research Laboratory, Department of Orthopaedics, The Netherlands University of Twente, Laboratory for Biomechanical Engineering, The Netherlands c Radboud University Medical Center, Spine Unit, Department of Orthopaedics, The Netherlands b
a r t i c l e
i n f o
Article history: Received 23 April 2013 Received in revised form 7 March 2014 Accepted 23 March 2014 Keywords: Spine Vertebral fractures Percutaneous vertebroplasty Prophylactic vertebroplasty Biomechanics Osteoporosis
a b s t r a c t Adjacent level vertebral fractures are common in patients with osteoporotic wedge fractures, but can theoretically be prevented with prophylactic vertebroplasty. Previous tests on prophylactic vertebroplasties have been performed under axial loading, while in vivo changes in spinal alignment likely cause off-axis loads. In this study we determined whether prophylactic vertebroplasty can also reduce the fracture risk under off-axis loads. In a previous study, we tested vertebral bodies that were loaded axially or 20◦ off-axis representing vertebrae in an unfractured spine or vertebrae adjacent to a wedge fracture, respectively. In the current study, vertebral failure load and stiffness of our previously tested vertebral bodies were compared to those of a new group of vertebral bodies that were filled with bone cement and then loaded 20◦ off-axis. These vertebral bodies represented adjacent-level vertebrae with prophylactic bone cement filling. Prophylactic augmentation resulted in failure loads that were comparable to those of the 0◦ group, and 32% greater than the failure loads of the 20◦ group. The stiffness of the prophylacticly augmented vertebrae was 21% lower than that of the 0◦ group, but 27% higher than that of the 20◦ group. We conclude that prophylactic augmentation can decrease the fracture risk in a malaligned, osteoporotic vertebra. Whether this is enough to actually prevent additional vertebral fractures in vivo remains subject of further study. © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.
1. Introduction Vertebral compression fractures are the most common fracture type related to osteoporosis, with an estimated 1.4 million new fractures occurring worldwide every year [1]. Anterior wedge fractures (AO type A1, the most common fracture) [2] are associated with pain, decreased quality of life, and changed sagittal spinal alignment [3,4]. An accepted surgical treatment of an acute vertebral fracture is the injection of bone cement (percutaneous vertebroplasty). This procedure has received its fair share of criticism due to two placebo-controlled trials [5,6]. However, a more recent study shows that, when compared to conservative care, percutaneous vertebroplasty is an effective method to reduce pain and improves the quality of life of patients [7].
∗ Corresponding author at: Laboratory for Biomechanical Engineering, University of Twente, Department CTW, PO Box 217, 7500 AE Enschede, The Netherlands. Tel.: +31 53 4892436/4894855; fax: +31 53 4892287. E-mail address: [email protected] (J. Homminga).
After a first vertebral compression fracture the risk of additional vertebral fractures steeply increases [8,9], particularly in adjacent level vertebrae[9–12], thereby further deteriorating the patient’s health and wellbeing. Whether this increased risk is caused by previous vertebroplasties, changed local biomechanics, natural susceptibility of the thoracolumbar junction to fractures, natural progression of the underlying disease, or a combination of all of these factors remains the subject of debate. Prophylacticly filling the adjacent level vertebrae with bone cement (prophylactic vertebroplasty) can theoretically prevent new fractures and further deterioration of the patient’s health. In vitro experiments have indeed shown a beneficial effect of prophylactic vertebroplasty under central and eccentric axial loading [13–16]. However, there are no studies analyzing the potential benefits of prophylactic vertebroplasty while applying a direct shearing load. Although vertebrae in healthy spines are mainly loaded axially [17,18], shearing loads often occur after vertebral fractures and the accompanying changes in spinal alignment [19] and make osteoporotic vertebrae more susceptible to fractures [20]. It is therefore reasonable to assume that the effects of prophylactic filling might differ under off-axis loads.
http://dx.doi.org/10.1016/j.medengphy.2014.03.009 1350-4533/© 2014 IPEM. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
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Table 1 Distribution of the vertebrae over the various groups. Cadaver
1
2
3
4
Sex Age Dexa (T-score) 0◦ group 20◦ group Prophylactic group
Male 87 −2.3 L4, L1, T10 L5, T12, T11 L3, T9
Female 89 −4.4 L4, L1 L3, L2 L5, T12
Female 92 −4.8 L4, L1, T10 T12, T11 L3, L2
Female 85 −4.1 L4, L1, T10 L3, L2, T9 L5, T12, T11
In this paper we assessed the reinforcing effects of prophylactic vertebroplasty under off-axis loads using an in vitro biomechanical model. 2. Methods Four complete fresh frozen human spines (1 male and 3 female), were placed in a water basin, where the bone density of the L1–L4 region was measured using dual energy X-ray absorptiometry (DEXA). One of the authors (AJFH), an experienced orthopedic surgeon, reviewed spinal X-rays to exclude previously fractured vertebrae. Thirty-one vertebrae, from T9 to L5, were included in our study (Table 1) and excised from the spines, cleaned from soft tissue, and resected at the pedicles to allow placement in our test setup. Unfortunately, one vertebra was damaged during the dissection procedure and therefore excluded from the study. Nine vertebrae underwent a bipedicular vertebroplasty using PMMA (Vebroplast, European Medical Contract Manufacturing, The Netherlands). The vertebral bodies were emerged in a water bath to determine their volume and the bone cement was injected with a syringe in order to determine the volume that was injected during the experiment. As a guideline, we used the same vertebral filling percentage that previous studies used, which was around 20% [14–16]. The remaining twenty-one vertebrae were used in a previous study where we determined the effects of shearing loads [20]. In that study, the vertebrae were divided into two groups: an axial group (n = 11) in which unfilled vertebrae were loaded purely axially, and an off-axis group (n = 10), in which unfilled vertebrae were loaded under 20◦ off-axis loading (Table 1). The nine newly tested vertebrae, of the current study, were used to determine the effects of prophylactic vertebroplasty. After vertebroplasty, the nine vertebrae were CT-scanned (resolution: 1 mm × 0.488 mm × 0.488 mm), with which we determined the volume of each vertebral body, the volume of injected bone cement, and the areas of the upper and lower endplates (Mimics, Materialize N.V., Belgium). Subsequently, both endplates of each vertebra were cast in bone cement using a previously designed and used mold [20,21]. The bone cement on the endplates (“cement caps”) allowed good placement in our testing setup and allowed an even load distribution across the endplate. The nine vertebrae were then loaded such that the load was directed through the center of the vertebral corpus but 20◦ tilted in the sagittal plane, giving it a posterior–anterior component as well as an axial component (Fig. 1). The 20◦ loading angle mimicked in vivo loading conditions on vertebrae adjacent to a fractured vertebra. Each filled vertebrae was compressed to failure under displacement control (2 mm/min), while measuring force with a sampling rate of 10 Hz. Failure load was defined as the highest registered force. Stiffness was defined as the slope of the linear part of the force–displacement curve, prior to failure. We compared stiffness, failure load, and endplate areas of the prophylactically filled vertebrae (n = 9) with the same parameters of the previously performed crush experiment on unfilled vertebrae [20]. As it is known that vertebral size influences vertebral strength [23], specimens were allocated based on spinal level. For
Fig. 1. Side view of the test setup. The 20◦ off axis load application setting is depicted.
example: if L2, L1, and T12 of one cadaver were allocated to the 20◦ off-axis, 0◦ axial and prophylactic group, respectively, then in a second cadaver L2, L1, and T12 would be allocated to the prophylactic, 0◦ axial and 20◦ off-axis group, respectively (Table 1). In this way we prevented that one group would always have bigger (and thus stronger) vertebrae than the other group, which could bias the data. All three groups contained vertebrae from all four cadavers, minimizing effects of inter-donor variability. Endplate area, failure load and stiffness were checked for normality (Kolmogorov–Smirnov test) and compared (one-way ANOVA, with an LSD post hoc test), where significance was set to p < 0.05. All tests were performed with the statistical package SPSS (SPSS Inc., USA). 3. Results From the CT images we determined that the average volume of injected bone cement was 8.4 ml (SD: 2.1 ml), and that the average vertebral body filling percentage was 22.3% (SD = 5.4%), close to the 20% target fill percentage. Measured endplate areas, stiffness and failure loads were all normally distributed. Mean endplate areas were not significantly different between the three measured groups (Table 2). The mean failure load of the prophylactically treated group, loaded under 20◦ , was 2850 N (SD = 703 N), which was significantly higher than the failure load of the unfilled 20◦ group (2163 N,
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
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R. Aquarius et al. / Medical Engineering & Physics xxx (2014) xxx–xxx Table 2 The mean endplate area (and SD) for all three groups. Group ◦
0 degree group 20◦ degree group Prophylactic group
Mean endplate area (mm2 )
Standard deviation (mm2 )
1474.7 1569.4 1510.7
443.2 456.4 303.0
Fig. 2. The average failure load (and SD) for all three groups.
Fig. 3. The average stiffness (and SD) for all three groups.
SD = 670 N, p = 0.03) and comparable to the mean failure load of the unfilled 0◦ group (2845 N, SD = 591 N, p = 0.99, Fig. 2). The mean stiffness of the prophylactically treated group, loaded under 20◦ , was 3156 N/mm (SD = 582 N/mm), which was significantly higher than the stiffness of the unfilled 20◦ group (2478 N/mm, SD = 453 N/mm, p = 0.04), but significantly lower than the stiffness of the unfilled 0◦ group (3979 N/mm, SD = 928 N/mm, p = 0.01, Fig. 3). 4. Discussion An initial vertebral compression fracture steeply increases the risk of additional adjacent-level vertebral fractures [9–12]. In this study we assessed whether prophylactic vertebroplasty could reinforce cadaver vertebrae, when taking sagittal malalignment and the accompanying (off-axis) load shift into account [19]. The most important result of this study was that prophylactic augmentation makes vertebrae, on an average, 32% stronger under off-axis loads. The failure load of these vertebrae was comparable to axially loaded (but unfilled) vertebrae. Previous studies on prophylactic filling also found that (axial) failure loads significantly increased [14–16]. The main difference between these studies and ours is that we used an off-axis load rather than an axial load [14,16]. We demonstrated a similar increase in failure load under off-axis loads.
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Thus, in vitro studies on single vertebrae have demonstrated that prophylactic filling reinforces vertebrae under both off-axis and on-axis loading. Although this suggests a clinical benefit, the real spine is more complex than a single vertebra. The question remains whether or not prophylactic filling can prevent adjacent vertebra from fracturing? The results from one multi-vertebrae in vitro study cautiously suggests that prophylactic filling of adjacent vertebrae might indeed prevent their fracture [24], while another study found no effect of prophylactic vertebroplasty at all [13]. The sparsely available clinical data is also inconclusive about the protective effects of prophylactic vertebroplasty [25,26]. In our results the failure loads in the prophylactic group and the 0◦ group were similar, indicating that the fracture risk of a prophylactically augmented vertebra returns to pre-fracture values. Whether it is enough to actually prevent a fracture remains inconclusive. Previous findings indicated only weak correlations between filling percentage and strength restoration after a fracture [27]. A reason for this observation might be the various ways in which the cement is distributed within the vertebral body. Endplate-toendplate filling for example, can dramatically increase the strength of reinforced vertebrae [28,29]. In our study the two vertebrae with the highest filling percentage (cadaver 4, T12: 34.2%, and cadaver 4, t11: 27%) showed endplate-to-endplate filling, but remarkably, did not show higher failure loads than vertebrae with no or partial endplate-to-endplate filling. The CT-images of these two highly filled vertebrae showed that the shape of the cement filling is “balllike”, with a smooth surface and no irregular shapes or cement protrusions (Fig. 4, top row), while the cement filling in the other vertebrae had very irregular shapes (Fig. 4, bottom row). This raises the question whether there is an “optimum” for the amount of cement filling: too little cement will only partially reinforce the vertebra [15], while too much cement injection might cause a loss in reinforcing capacity. With the injection of high amounts of bone cement, high intra-vertebral pressures are likely [30], which might damage the remaining trabeculae by “pushing” them to the side, resulting in the “ball-like” cement filling. As only the outside of such fillings can contact the bone, reinforcement is likely to be less effective than in vertebrae with cement fillings that are more entangled in the remaining bone. This hypothesis is speculative, but interesting for future research. The augmentation of vertebral bodies with bone cement can possibly also induce new adjacent vertebral fractures. In case of prophylactic vertebroplasty, this would be a rather disappointing side-effect, as the treatment aims to prevent consecutive fractures. It has been suggested that the relatively stiff bone cement injected into the osteoporotic bone causes stress peaks on the endplates, leading to fractures at the adjacent levels [31–33]. However, clinical studies in which vertebroplasty groups are compared to conservatively treated control groups, show no trends toward increased adjacent level fracture risks in the vertebroplasty groups [5,7,10]. A possible reason for this discrepancy is the fact that in experimental studies generally more bone cement is injected (about 8.8 ml [31], 33% of vertebral body volume [33]) than in the clinical studies (about 4.1 ml7 , but sometimes as little as 2.8 ml5 ), which may exaggerate negative effects. Fortunately, more recent evidence, based on experimental studies, suggests that vertebroplasty can restore mechanical properties [34] and does not necessarily lead to increased adjacent level loading [35]. These results are more in line with clinical findings and suggest the beneficial possibilities of the prophylactic vertebroplasty procedure. This study has a few limitations that should be considered. First, the loading condition used in this experiment was a simplification of the true in vivo loading situation. The 20◦ was based on the angle that typically results from a single wedge fracture [22]. However, such a wedge-like deformity of the vertebral body does not necessarily imply that the loading direction of the adjacent level vertebra
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
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Fig. 4. Different typical shapes of cement filling. Top row: “ball-like” shape in the vertebra with the lowest failure load (2121 N) but with one of the highest filling percentages (27.0%) in the prophylactic group. Bottom row: irregular shapes and branches in the vertebra with the highest failure load (3994 N) but with one of the lowest filling percentages (18.2%) in the prophylactic group.
also shows a 20◦ shift. Muscles, ligaments and joint capsules can all influence this load shift, but the true size of the resulting shift cannot be deduced from the current literature. As a result, our experiment should be seen as “proof of principle”. Second, to reach the 20% vertebral filling suggested in literature [14–16], we injected relatively high amounts of bone cement (8.4 ml, SD: 2.1 ml) compared to clinically used amounts (2–6 ml [25]). We therefore think that more clinically realistic volumes and more advanced filling materials and delivery techniques are important topics for future in vitro research. Finally, we were unable to include the potential change in load transfer through the facet joints within our test setup. It is reasonable to assume that the effect of prophylactic filling will be less dramatic when the facet joints are taken into account. However, the precise role of the facet joints on the off-axis failure mechanisms requires further study. In conclusion, we demonstrated in our in vitro tests that prophylactic augmentation can decrease fracture risk in misaligned, osteoporotic vertebrae adjacent to a wedge fracture. Whether this reinforcement is enough to actually prevent additional vertebral fractures in clinical situations, remains subject of further study. Funding Our project was funded by “fonds NutsOhra” foundation (grant number 1002-045). Our sponsor had no involvement in the design of the study, nor the collection, analysis or interpretation of the data, nor the writing or submitting of the manuscript. Ethical approval Not required. Acknowledgements We would like to thank the “Fonds NutsOhra” foundation (grant number 1002-045) for their funding, the Department of Anatomy for providing the cadavers, and Willem van de Wijdeven for the practical help with the experiments.
Conflict of interest The authors have no competing interests to declare.
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[15] Sun K, Liebschner MAK. Biomechanics of prophylactic vertebral reinforcement. Spine 2004;13:1428–35. [16] Higgins KB, Harten RD, Langrana N, Reiter MF. Biomechanical effects of unipedicular vertebroplasty on intact vertebrae. Spine 2003;28:1540–8. [17] Patwardhan AG, Havey RM, Meade KP, Lee B, Dunlap B. A follower load increases the load-carrying capacity of the lumbar spine in compression. Spine 1999;24:1003–9. [18] Rohlmann A, Graichen F, Bender A, Kayser R, Bergmann G. Loads on a telemeterized vertebral body replacement measured in three patients within the first postoperative month. Clin Biomech 2008;23:147–58. [19] Briggs AM, Wrighley TV, van Dieën JH, Phillips B, Lo SK, Greig AM, et al. The effect of osteoporotic vertebral fracture on predicted spinal loads in vivo. Eur Spine J 2006;15:1785–95. [20] Aquarius R, Homminga J, Verdonschot N, Tanck E. The fracture risk of adjacent vertebrae is increased by the changed loading direction after a wedge fracture. Spine 2011;36:E408–12. [21] Buckley JM, Kuo CC, Cheng LC, Loo K, Motherway J, Slyfield C, et al. Relative strength of thoracic vertebrae in axial compression versus flexion. Spine J 2009;9:478–85. [22] Rhyne III A, Banit D, Laxer E, Odum S, Nussman D. Report of eighty-two thoracolumbar osteoporortic vertebral fractures. J Orthop Trauma 2004;18:294–9. [23] Ruyssen-Witrand A, Gossec L, Kolta S, Dougados M, Roux C. Vertebral dimensions as risk factor of vertebral fracture in osteoporotic patients: a systematic literature review. Osteoporos Int 2007;18:1271–8. [24] Ciang CK, Wang YH, Yang CY, Yang BD, Wang JL. Prophylactic vertebroplasty may reduce the risk of adjacent intact vertebra from fatigue injury. An ex vivo biomechanical study. Spine 2009;34:356–64. [25] Becker S, Garoscio M, Meissner J, Tuschel A, Ogon M. Is there an indication for prophylactic balloon kyphoplasty? A pilot study. Clin Orthop Relat Res 2007;458:83–9.
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[26] Kobayashi N, Numaguchi Y, Fuwa S, Uemura A, Matsusako M, Okajima Y, et al. Prophylactic vertebroplasty: cement injection into non-fractured vertebral bodies during percutaneous vertebroplasty. Acad Radiol 2009;16:136–43. [27] Molloy S, Mathis JM, Belkoff SM. The effect of vertebral body percentage fill on mechanical behavior during percutaneous vertebroplasty. Spine 2003;28:1549–54. [28] Steens J, Verdonschot N, Aalsma AM, Hosman AJ. The influence of endplateto-endplate cement augmentation on vertebral strength and stiffness in vertebroplasty. Spine 2007;32:E419–22. [29] Chevalier Y, Pahr D, Charlebois M, Heini P, Schneider E, Zysset P. Cement distribution, volume, and compliance in vertebroplasty. Some answers from anatomy-based non-linear finite element study. Spine 2008;33: 1722–30. [30] Gravius S, Kraska N, Maus U, Mumme T, Berdel P, Weisskopf M. Intravertebral pressure during vertebroplasty – an in vitro study. Z Orthop Unfall 2009;147:43–7. [31] Berlemann U, Ferguson SJ, Nolte L-P, Heini PF. Adjacent vertebral failure after vertebroplasty. A biomechanical investigation. J Bone Joint Surg Br 2002;84B:748–52. [32] Baroud G, Nemes J, Heini P, Steffen T. Load shift of the intervertebral disc: a finite-element study. Eur Spine J 2003;12:421–6. [33] Polikeit A, Nolte LP, Ferguson SJ. The effect of cement augmentation on the load transfer in an osteoporotic functional spinal unit; finite-element analysis. Spine 2003;28:991–6. [34] Luo J, Skrzypiec DM, Pollintine P, Adams MA, Annesley-Williams DJ, Dolan P. Mechanical efficiency of vertebroplasty: influence of cement type, BMD, fracture severity, and disc degeneration. Bone 2007;40:1110–9. [35] Aquarius R, van der Zijden AM, Homminga J, Verdonschot N, Tanck E. Does bone cement in percutaneous vertebroplasty act as a stress riser? Spine 2013;38:2092–7.
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
ARTICLE IN PRESS Medical Engineering & Physics xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Medical Engineering & Physics journal homepage: www.elsevier.com/locate/medengphy
Technical note
Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study René Aquarius a , Jasper Homminga b,∗ , Allard Jan Frederik Hosman c , Nico Verdonschot a,b , Esther Tanck a a
Radboud University Medical Center, Orthopaedic Research Laboratory, Department of Orthopaedics, The Netherlands University of Twente, Laboratory for Biomechanical Engineering, The Netherlands c Radboud University Medical Center, Spine Unit, Department of Orthopaedics, The Netherlands b
a r t i c l e
i n f o
Article history: Received 23 April 2013 Received in revised form 7 March 2014 Accepted 23 March 2014 Keywords: Spine Vertebral fractures Percutaneous vertebroplasty Prophylactic vertebroplasty Biomechanics Osteoporosis
a b s t r a c t Adjacent level vertebral fractures are common in patients with osteoporotic wedge fractures, but can theoretically be prevented with prophylactic vertebroplasty. Previous tests on prophylactic vertebroplasties have been performed under axial loading, while in vivo changes in spinal alignment likely cause off-axis loads. In this study we determined whether prophylactic vertebroplasty can also reduce the fracture risk under off-axis loads. In a previous study, we tested vertebral bodies that were loaded axially or 20◦ off-axis representing vertebrae in an unfractured spine or vertebrae adjacent to a wedge fracture, respectively. In the current study, vertebral failure load and stiffness of our previously tested vertebral bodies were compared to those of a new group of vertebral bodies that were filled with bone cement and then loaded 20◦ off-axis. These vertebral bodies represented adjacent-level vertebrae with prophylactic bone cement filling. Prophylactic augmentation resulted in failure loads that were comparable to those of the 0◦ group, and 32% greater than the failure loads of the 20◦ group. The stiffness of the prophylacticly augmented vertebrae was 21% lower than that of the 0◦ group, but 27% higher than that of the 20◦ group. We conclude that prophylactic augmentation can decrease the fracture risk in a malaligned, osteoporotic vertebra. Whether this is enough to actually prevent additional vertebral fractures in vivo remains subject of further study. © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.
1. Introduction Vertebral compression fractures are the most common fracture type related to osteoporosis, with an estimated 1.4 million new fractures occurring worldwide every year [1]. Anterior wedge fractures (AO type A1, the most common fracture) [2] are associated with pain, decreased quality of life, and changed sagittal spinal alignment [3,4]. An accepted surgical treatment of an acute vertebral fracture is the injection of bone cement (percutaneous vertebroplasty). This procedure has received its fair share of criticism due to two placebo-controlled trials [5,6]. However, a more recent study shows that, when compared to conservative care, percutaneous vertebroplasty is an effective method to reduce pain and improves the quality of life of patients [7].
∗ Corresponding author at: Laboratory for Biomechanical Engineering, University of Twente, Department CTW, PO Box 217, 7500 AE Enschede, The Netherlands. Tel.: +31 53 4892436/4894855; fax: +31 53 4892287. E-mail address: [email protected] (J. Homminga).
After a first vertebral compression fracture the risk of additional vertebral fractures steeply increases [8,9], particularly in adjacent level vertebrae[9–12], thereby further deteriorating the patient’s health and wellbeing. Whether this increased risk is caused by previous vertebroplasties, changed local biomechanics, natural susceptibility of the thoracolumbar junction to fractures, natural progression of the underlying disease, or a combination of all of these factors remains the subject of debate. Prophylacticly filling the adjacent level vertebrae with bone cement (prophylactic vertebroplasty) can theoretically prevent new fractures and further deterioration of the patient’s health. In vitro experiments have indeed shown a beneficial effect of prophylactic vertebroplasty under central and eccentric axial loading [13–16]. However, there are no studies analyzing the potential benefits of prophylactic vertebroplasty while applying a direct shearing load. Although vertebrae in healthy spines are mainly loaded axially [17,18], shearing loads often occur after vertebral fractures and the accompanying changes in spinal alignment [19] and make osteoporotic vertebrae more susceptible to fractures [20]. It is therefore reasonable to assume that the effects of prophylactic filling might differ under off-axis loads.
http://dx.doi.org/10.1016/j.medengphy.2014.03.009 1350-4533/© 2014 IPEM. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
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Table 1 Distribution of the vertebrae over the various groups. Cadaver
1
2
3
4
Sex Age Dexa (T-score) 0◦ group 20◦ group Prophylactic group
Male 87 −2.3 L4, L1, T10 L5, T12, T11 L3, T9
Female 89 −4.4 L4, L1 L3, L2 L5, T12
Female 92 −4.8 L4, L1, T10 T12, T11 L3, L2
Female 85 −4.1 L4, L1, T10 L3, L2, T9 L5, T12, T11
In this paper we assessed the reinforcing effects of prophylactic vertebroplasty under off-axis loads using an in vitro biomechanical model. 2. Methods Four complete fresh frozen human spines (1 male and 3 female), were placed in a water basin, where the bone density of the L1–L4 region was measured using dual energy X-ray absorptiometry (DEXA). One of the authors (AJFH), an experienced orthopedic surgeon, reviewed spinal X-rays to exclude previously fractured vertebrae. Thirty-one vertebrae, from T9 to L5, were included in our study (Table 1) and excised from the spines, cleaned from soft tissue, and resected at the pedicles to allow placement in our test setup. Unfortunately, one vertebra was damaged during the dissection procedure and therefore excluded from the study. Nine vertebrae underwent a bipedicular vertebroplasty using PMMA (Vebroplast, European Medical Contract Manufacturing, The Netherlands). The vertebral bodies were emerged in a water bath to determine their volume and the bone cement was injected with a syringe in order to determine the volume that was injected during the experiment. As a guideline, we used the same vertebral filling percentage that previous studies used, which was around 20% [14–16]. The remaining twenty-one vertebrae were used in a previous study where we determined the effects of shearing loads [20]. In that study, the vertebrae were divided into two groups: an axial group (n = 11) in which unfilled vertebrae were loaded purely axially, and an off-axis group (n = 10), in which unfilled vertebrae were loaded under 20◦ off-axis loading (Table 1). The nine newly tested vertebrae, of the current study, were used to determine the effects of prophylactic vertebroplasty. After vertebroplasty, the nine vertebrae were CT-scanned (resolution: 1 mm × 0.488 mm × 0.488 mm), with which we determined the volume of each vertebral body, the volume of injected bone cement, and the areas of the upper and lower endplates (Mimics, Materialize N.V., Belgium). Subsequently, both endplates of each vertebra were cast in bone cement using a previously designed and used mold [20,21]. The bone cement on the endplates (“cement caps”) allowed good placement in our testing setup and allowed an even load distribution across the endplate. The nine vertebrae were then loaded such that the load was directed through the center of the vertebral corpus but 20◦ tilted in the sagittal plane, giving it a posterior–anterior component as well as an axial component (Fig. 1). The 20◦ loading angle mimicked in vivo loading conditions on vertebrae adjacent to a fractured vertebra. Each filled vertebrae was compressed to failure under displacement control (2 mm/min), while measuring force with a sampling rate of 10 Hz. Failure load was defined as the highest registered force. Stiffness was defined as the slope of the linear part of the force–displacement curve, prior to failure. We compared stiffness, failure load, and endplate areas of the prophylactically filled vertebrae (n = 9) with the same parameters of the previously performed crush experiment on unfilled vertebrae [20]. As it is known that vertebral size influences vertebral strength [23], specimens were allocated based on spinal level. For
Fig. 1. Side view of the test setup. The 20◦ off axis load application setting is depicted.
example: if L2, L1, and T12 of one cadaver were allocated to the 20◦ off-axis, 0◦ axial and prophylactic group, respectively, then in a second cadaver L2, L1, and T12 would be allocated to the prophylactic, 0◦ axial and 20◦ off-axis group, respectively (Table 1). In this way we prevented that one group would always have bigger (and thus stronger) vertebrae than the other group, which could bias the data. All three groups contained vertebrae from all four cadavers, minimizing effects of inter-donor variability. Endplate area, failure load and stiffness were checked for normality (Kolmogorov–Smirnov test) and compared (one-way ANOVA, with an LSD post hoc test), where significance was set to p < 0.05. All tests were performed with the statistical package SPSS (SPSS Inc., USA). 3. Results From the CT images we determined that the average volume of injected bone cement was 8.4 ml (SD: 2.1 ml), and that the average vertebral body filling percentage was 22.3% (SD = 5.4%), close to the 20% target fill percentage. Measured endplate areas, stiffness and failure loads were all normally distributed. Mean endplate areas were not significantly different between the three measured groups (Table 2). The mean failure load of the prophylactically treated group, loaded under 20◦ , was 2850 N (SD = 703 N), which was significantly higher than the failure load of the unfilled 20◦ group (2163 N,
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
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R. Aquarius et al. / Medical Engineering & Physics xxx (2014) xxx–xxx Table 2 The mean endplate area (and SD) for all three groups. Group ◦
0 degree group 20◦ degree group Prophylactic group
Mean endplate area (mm2 )
Standard deviation (mm2 )
1474.7 1569.4 1510.7
443.2 456.4 303.0
Fig. 2. The average failure load (and SD) for all three groups.
Fig. 3. The average stiffness (and SD) for all three groups.
SD = 670 N, p = 0.03) and comparable to the mean failure load of the unfilled 0◦ group (2845 N, SD = 591 N, p = 0.99, Fig. 2). The mean stiffness of the prophylactically treated group, loaded under 20◦ , was 3156 N/mm (SD = 582 N/mm), which was significantly higher than the stiffness of the unfilled 20◦ group (2478 N/mm, SD = 453 N/mm, p = 0.04), but significantly lower than the stiffness of the unfilled 0◦ group (3979 N/mm, SD = 928 N/mm, p = 0.01, Fig. 3). 4. Discussion An initial vertebral compression fracture steeply increases the risk of additional adjacent-level vertebral fractures [9–12]. In this study we assessed whether prophylactic vertebroplasty could reinforce cadaver vertebrae, when taking sagittal malalignment and the accompanying (off-axis) load shift into account [19]. The most important result of this study was that prophylactic augmentation makes vertebrae, on an average, 32% stronger under off-axis loads. The failure load of these vertebrae was comparable to axially loaded (but unfilled) vertebrae. Previous studies on prophylactic filling also found that (axial) failure loads significantly increased [14–16]. The main difference between these studies and ours is that we used an off-axis load rather than an axial load [14,16]. We demonstrated a similar increase in failure load under off-axis loads.
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Thus, in vitro studies on single vertebrae have demonstrated that prophylactic filling reinforces vertebrae under both off-axis and on-axis loading. Although this suggests a clinical benefit, the real spine is more complex than a single vertebra. The question remains whether or not prophylactic filling can prevent adjacent vertebra from fracturing? The results from one multi-vertebrae in vitro study cautiously suggests that prophylactic filling of adjacent vertebrae might indeed prevent their fracture [24], while another study found no effect of prophylactic vertebroplasty at all [13]. The sparsely available clinical data is also inconclusive about the protective effects of prophylactic vertebroplasty [25,26]. In our results the failure loads in the prophylactic group and the 0◦ group were similar, indicating that the fracture risk of a prophylactically augmented vertebra returns to pre-fracture values. Whether it is enough to actually prevent a fracture remains inconclusive. Previous findings indicated only weak correlations between filling percentage and strength restoration after a fracture [27]. A reason for this observation might be the various ways in which the cement is distributed within the vertebral body. Endplate-toendplate filling for example, can dramatically increase the strength of reinforced vertebrae [28,29]. In our study the two vertebrae with the highest filling percentage (cadaver 4, T12: 34.2%, and cadaver 4, t11: 27%) showed endplate-to-endplate filling, but remarkably, did not show higher failure loads than vertebrae with no or partial endplate-to-endplate filling. The CT-images of these two highly filled vertebrae showed that the shape of the cement filling is “balllike”, with a smooth surface and no irregular shapes or cement protrusions (Fig. 4, top row), while the cement filling in the other vertebrae had very irregular shapes (Fig. 4, bottom row). This raises the question whether there is an “optimum” for the amount of cement filling: too little cement will only partially reinforce the vertebra [15], while too much cement injection might cause a loss in reinforcing capacity. With the injection of high amounts of bone cement, high intra-vertebral pressures are likely [30], which might damage the remaining trabeculae by “pushing” them to the side, resulting in the “ball-like” cement filling. As only the outside of such fillings can contact the bone, reinforcement is likely to be less effective than in vertebrae with cement fillings that are more entangled in the remaining bone. This hypothesis is speculative, but interesting for future research. The augmentation of vertebral bodies with bone cement can possibly also induce new adjacent vertebral fractures. In case of prophylactic vertebroplasty, this would be a rather disappointing side-effect, as the treatment aims to prevent consecutive fractures. It has been suggested that the relatively stiff bone cement injected into the osteoporotic bone causes stress peaks on the endplates, leading to fractures at the adjacent levels [31–33]. However, clinical studies in which vertebroplasty groups are compared to conservatively treated control groups, show no trends toward increased adjacent level fracture risks in the vertebroplasty groups [5,7,10]. A possible reason for this discrepancy is the fact that in experimental studies generally more bone cement is injected (about 8.8 ml [31], 33% of vertebral body volume [33]) than in the clinical studies (about 4.1 ml7 , but sometimes as little as 2.8 ml5 ), which may exaggerate negative effects. Fortunately, more recent evidence, based on experimental studies, suggests that vertebroplasty can restore mechanical properties [34] and does not necessarily lead to increased adjacent level loading [35]. These results are more in line with clinical findings and suggest the beneficial possibilities of the prophylactic vertebroplasty procedure. This study has a few limitations that should be considered. First, the loading condition used in this experiment was a simplification of the true in vivo loading situation. The 20◦ was based on the angle that typically results from a single wedge fracture [22]. However, such a wedge-like deformity of the vertebral body does not necessarily imply that the loading direction of the adjacent level vertebra
Please cite this article in press as: Aquarius R, et al. Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae: An in vitro cadaveric study. Med Eng Phys (2014), http://dx.doi.org/10.1016/j.medengphy.2014.03.009
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Fig. 4. Different typical shapes of cement filling. Top row: “ball-like” shape in the vertebra with the lowest failure load (2121 N) but with one of the highest filling percentages (27.0%) in the prophylactic group. Bottom row: irregular shapes and branches in the vertebra with the highest failure load (3994 N) but with one of the lowest filling percentages (18.2%) in the prophylactic group.
also shows a 20◦ shift. Muscles, ligaments and joint capsules can all influence this load shift, but the true size of the resulting shift cannot be deduced from the current literature. As a result, our experiment should be seen as “proof of principle”. Second, to reach the 20% vertebral filling suggested in literature [14–16], we injected relatively high amounts of bone cement (8.4 ml, SD: 2.1 ml) compared to clinically used amounts (2–6 ml [25]). We therefore think that more clinically realistic volumes and more advanced filling materials and delivery techniques are important topics for future in vitro research. Finally, we were unable to include the potential change in load transfer through the facet joints within our test setup. It is reasonable to assume that the effect of prophylactic filling will be less dramatic when the facet joints are taken into account. However, the precise role of the facet joints on the off-axis failure mechanisms requires further study. In conclusion, we demonstrated in our in vitro tests that prophylactic augmentation can decrease fracture risk in misaligned, osteoporotic vertebrae adjacent to a wedge fracture. Whether this reinforcement is enough to actually prevent additional vertebral fractures in clinical situations, remains subject of further study. Funding Our project was funded by “fonds NutsOhra” foundation (grant number 1002-045). Our sponsor had no involvement in the design of the study, nor the collection, analysis or interpretation of the data, nor the writing or submitting of the manuscript. Ethical approval Not required. Acknowledgements We would like to thank the “Fonds NutsOhra” foundation (grant number 1002-045) for their funding, the Department of Anatomy for providing the cadavers, and Willem van de Wijdeven for the practical help with the experiments.
Conflict of interest The authors have no competing interests to declare.
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