- Email: [email protected]
Biomechanical evaluation of kyphoplasty with calcium sulfate cement in a cadaveric osteoporotic vertebral compression fracture model
The Spine Journal 5 (2005) 489–493
Biomechanical evaluation of kyphoplasty with calcium sulfate cement in a cadaveric osteoporotic vertebral compression fracture model Andrew Perry, MDa, Andrew Mahar, MScb, Jennifer Massie, MSa, Noemi Arrieta, BSa, Steven Garfin, MDa, Choll Kim, MD, PhDa,* a Veterans Administration and University of California, San Diego, 3350 La Jolla Village Drive, San Diego, CA 92161, USA Biomechanics Laboratory, Children’s Hospital, University of California, San Diego, 3020 Children’s Way, San Diego, CA 92123, USA
b
Received 20 October 2004; accepted 15 March 2005
Abstract
BACKGROUND CONTEXT: Vertebral compression fractures can cause deformity, pain, and disability. Kyphoplasty involves percutaneous insertion of an inflatable balloon tamp into a fractured vertebra followed by injection of polymethylmethacrylate (PMMA) bone cement. PMMA has several disadvantages such as potential thermal necrosis and monomer toxicity. Calcium sulfate cement (CSC) is nontoxic, osteoconductive, and bioabsorbable. PURPOSE: To evaluate the biomechanical performance of CSC for kyphoplasty in cadaveric osteoporotic vertebral bodies. STUDY DESIGN: Destructive biomechanical tests using fresh cadaveric thoracolumbar vertebral bodies. METHODS: Thirty-three vertebral bodies (T9 to L4) from osteoporotic cadaveric spines were disarticulated, stripped of soft tissue, and measured for height and volume. Each vertebral body was compressed at 0.5 mm/s using a hinged plating system on a materials testing machine to create an anterior wedge fracture and reduce the anterior height by 25%. Pretreatment strength and stiffness were measured. Two KyphX inflatable balloon tamps were used to reexpand each vertebral body. After randomization, three groups were created: Group A–no cement; Group B–PMMA; Group C– calcium sulfate cement. Groups B and C were filled with the corresponding cement to 25% of the vertebral body volume. All vertebral bodies were then recompressed by 25% of the post-kyphoplasty anterior height to obtain posttreatment strength and stiffness. RESULTS: Treatment with PMMA restored vertebral strength to 127% of the intact level (4168.2 N⫾2288.7) and stiffness to 70% of the intact level (810.0 N/mm⫾380.6). Treatment with CSC restored strength to 108% of the intact level (3429.6 N⫾2440.7) and stiffness to 46% of the intact level (597.7 N/mm⫾317.5). CSC and PMMA were not significantly different for strength restoration (p⫽.4). Significantly greater strength restoration was obtained with either PMMA or CSC, compared with the control group (p⫽.003 and .03, respectively). Stiffness restoration tended to be greater with PMMA than for CSC, but this difference was not statistically significant (p⫽.1). Both cements had significantly greater stiffness when compared with the control group (p⫽.001 and p⫽.04, respectively). CONCLUSIONS: Use of CSC for kyphoplasty yields similar vertebral body strength and stiffness as compared with PMMA. It may be a useful alternative bone cement for kyphoplasty. Further studies are required to assess the bioabsorption of CSCs after kyphoplasty in vivo. 쑖 2005 Elsevier Inc. All rights reserved.
Keywords:
Calcium sulfate cement; Polymethylmethacrylate; Spine biomechanics; Kyphoplasty; Vertebroplasty; Vertebral compression fracture
FDA device/drug status: not approved for this indication (MIIGX3, Wright Medical Inc., Arlington, TN). Nothing of value received from a commercial entity related to this manuscript.
1529-9430/05/$ – see front matter doi:10.1016/j.spinee.2005.03.011
쑖 2005 Elsevier Inc. All rights reserved.
* Corresponding author. Assistant Professor-Spine Surgery, Department of Orthopaedic Surgery, University of California, San Diego VA Medical Center, La Jolla, California, 3350 La Jolla Village Drive #112D, San Diego, CA 92161. Tel.: (858) 657-8248; fax: (858) 657-8260. E-mail address: [email protected] (C. Kim)
490
A. Perry et al. / The Spine Journal 5 (2005) 489–493
Introduction
Materials and methods
Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of the skeleton, leading to bone fragility and increased fracture risk [1]. Approximately 700,000 vertebral compression fractures occur annually in the United States, mainly secondary to osteoporosis [2,3]. A patient with a single osteoporotic vertebral fracture is at higher risk of sustaining an additional vertebral fracture [4]. Painful osteoporotic vertebral fractures can have significant effects on quality of life and physical function [5]. The mortality rate also increases with the number of vertebrae fractured [6]. Chronic pain and decreased mobility can lead to a depressed mood and loss of independence. Vertebral augmentation via vertebroplasty or kyphoplasty involves the percutaneous injection of bone cement into the fractured vertebral body [7]. Both vertebroplasty and kyphoplasty have been shown to provide rapid pain relief with relatively low complication rates [8]. The most commonly used cement is polymethylmethacrylate (PMMA). Unfortunately, PMMA has several potential disadvantages. PMMA is not bioabsorbable and remains permanently in the body. Its unreacted monomer is toxic, and its high polymerization temperature has resulted in temperature readings as much as 113⬚C on the anterior cortex of treated vertebral bodies in cadaveric studies [9]. The high compressive strength and stiffness of PMMA causes a biomechanical mismatch between treated and untreated vertebral levels which may increase the risk of adjacent-level fractures [10]. Recently, attempts have been made to develop bioabsorbable bone cements that address these potential problems. Cements that have undergone ex vivo biomechanical testing include a carbonated apatite cement (Norian, Cupertino, CA), a bioactive cement (Orthocomp; Orthovita, Malvern, PA), and a calcium phosphate cement (α-BSM; ETEX Corp., Cambridge, MA) [11–13]. All have been shown to possess comparable biomechanical profiles as PMMA in simulated cadaveric vertebral compression fractures. Calcium sulfate cements (CSCs) have been used successfully as bone void fillers for over 100 years [14,15]. The osteoconductive properties of such cements have been known for more than 40 years. These cements have low setting temperatures compatible with living tissue [16]. They encourage vascular in-growth and are replaced by host bone by creeping substitution [17]. Therefore, CSCs possess many favorable properties for potential use in vertebral augmentation. Little is known, however, about the biomechanical performance of these cements for this application. The purpose of the current study was to evaluate the biomechanical profile of a calcium sulfate cement preparation (MIIG X3; Wright Medical Inc., Arlington, TN) for kyphoplasty in a simulated osteoporotic vertebral compression fracture model.
Thirty-three vertebral bodies (T9 to L4) were harvested from two male and three female osteoporotic cadaveric spines (range of age at death, 73 to 89 years). The spines selected had no radiographic evidence of tumors, gross kyphosis, scoliosis, or previous surgery. Each spine was scanned with a Delphi W QDR Series DEXA Scanner (Hologic, Inc., Bedford, MA) to obtain the bone mineral density (BMD) of each vertebra. These BMDs were then compared with the corresponding young normal mean values and each difference expressed as a standard deviation score (ie, T score) to estimate the degree of osteoporosis. Specimens The vertebrae were stripped of soft tissue and the posterior elements removed to facilitate testing. The anterior, posterior, right and left lateral heights of the vertebral bodies were measured with calipers accurate to 0.01 mm (Mattoon MTI Corp., Aurora, IL). Molds of the superior and inferior end plates were made for each vertebral body using an epoxy filler (Bondo; Bondo Corp., Atlanta, GA) to ensure uniform and even loading during compression testing. Vertebral body volumes were calculated using the Archimedean water displacement principle. Volumes obtained in this manner have been shown to be in good agreement with that calculated using vertebral body dimensions obtained from plain films [18,19]. Mechanical testing Each vertebral body was compressed at 0.5 mm per second using a hinged-plated device in a materials testing machine (MTS, Eden Prairie, MN) to create an anterior wedge-fracture and reduce anterior height by 25% of the intact value. Force (N) and displacement (mm) data were recorded at 10 Hz. Stiffness data for each specimen were obtained from the gradient of the load-displacement graph between 500 and 1500 N. Vertebral augmentation The vertebral bodies (T9-L4) were randomly assigned to one of three groups: Group A–No cement; Group B–PMMA (Simplex P; Howmedica Inc., Rutherford, NJ); Group C– calcium sulfate cement (MIIG X3; Wright Medical Inc., Arlington, TN). Kyphoplasty was performed with each balloon tamp (KyphX bone tamp; Kyphon Inc., Sunnyvale, CA) inflated to a maximum of 2 cc or until 220 psi was recorded. Groups B and C were then injected bi-pedicularly with their respective bone cements within the cancellous void to 25% volume fill. For Group B, 40 g of Simplex P powder was combined with approximately 18 g of barium sulfate to create a powder with 32% barium sulfate by dry weight to enhance visualization of the cement under fluoroscopy [20]. PMMA monomer liquid was added to this powder giving a
A. Perry et al. / The Spine Journal 5 (2005) 489–493
monomer to powder ratio of 0.83 mL/g. For CSC, adequate radiographic visualization was achieved by mixing the cement according to the manufacturer’s guidelines of cement preparation without the need for additional barium sulfate. After cement injection, all vertebral bodies were wrapped in saline-soaked gauze and stored at 4⬚C for 24 hours. The anterior, posterior, and lateral heights of each specimen were remeasured and anteroposterior and lateral radiographic images were taken to confirm accurate cement placement. All vertebral bodies were then recompressed by 25% of the new anterior height to obtain posttreatment data, as described previously. Statistical analysis Statistical testing was performed using analysis of variance to compare differences in BMD, T-scores, and vertebral body volumes between groups. A two-way analysis of variance was used to detect the effect of cement type on pretreatment and posttreatment strength and stiffness. Significance was set as p⬍.05. Results No statistically significant differences in mean BMD or T-scores were found between any of the pretreatment groups (p⬍.05). In addition, no significant differences in vertebral body volume or anterior vertebral body heights were found. The average T-score of the vertebral bodies was ⫺2.7 (range ⫺1.5 to ⫺4.5). The average volume of cement injected into each vertebral body was 7.5 cc (range 2.5 cc to 11.75 cc). There was no significant difference in the mean volume of PMMA or CSC that was injected into either of these groups. The average BMD of these specimens was 0.75 g/cm3 (range 0.56 g/cm3 to 0.90 g/cm3). As expected, mean pretreatment strengths of groups A, B, and C were not significantly different from each other (3152.9 N⫾1176.2, 3475.1 N⫾1559.4, and 3239.4 N⫾1204.6, respectively). Similarly, pretreatment stiffness for groups A, B, and C were also not significantly different (1188.3 N⫾369.1, 1176.0 N⫾321.0, and 1478.9N⫾538.4, respectively). CSC showed similar filling characteristics to that in clinical practice with PMMA (Fig. 1).
491
Posttreatment strength and stiffness data are shown in Figures 2 and 3. Treatment with PMMA restored vertebral strength to 127% of the intact level (4168.2 N⫾288.1) and stiffness to 70% of the intact level (810.1 N/mm⫾380.5). Treatment with CSC restored strength to 108% of the intact level (3429.7 N⫾2440.3) and stiffness to 46% of the intact level (598.7 N/mm⫾318.0). There was no statistically significant difference in strength between groups B and C (p⫽.4). Both PMMA and CSC provided significantly higher strength restoration than bone tamp inflation only (Group A), (p⫽.003 and .03, respectively). The average stiffness of Group B (PMMA) was higher than Group C (CSC), but was not statistically significant (p⫽.1). Both PMMA and CSC provided significantly greater stiffness when either was compared with Group A (p⫽.001 and p⫽.04, respectively).
Discussion Although, vertebroplasty and kyphoplasty with PMMA are effective in providing pain relief of vertebral compression fractures, there have been theoretic concerns about potential adverse effects with the use of such acrylic cements. These concerns include the possibility of thermal injury to surrounding tissue and toxicity from the unreacted monomer [9]. The potential for adjacent level fractures as a result of PMMA’s exceedingly high compressive strength and stiffness profile is also of concern. The ideal bone cement should be biodegradable, nontoxic, have a low setting temperature, and have a biomechanical profile closer to that of human bone [10]. In the current study, the biomechanical properties of vertebral bodies treated with kyphoplasty using either CSC or PMMA were compared. Molloy et al. used standard amounts of PMMA cement (2, 4, 6, and 8 mL) for either thoracic (T6-T10), thoracolumbar (T11-L1), or lumbar (L2-L5) vertebrae during vertebroplasty [21]. Linear regression analysis of their results found a weak relation between percentage fill and restored strength and stiffness (r2⫽.21, r2⫽.27 respectively). Full strength restoration was obtained with roughly a 20% fill and full stiffness restoration with a 30%
Fig. 1. Radiograph of L1 vertebral body with calcium sulfate cement. (a) axial view; (b) lateral view.
492
A. Perry et al. / The Spine Journal 5 (2005) 489–493
Pre Treatment Post Treatment 5000
*
4500
N
NS
NS
4000
*
NS
NS
3500 3000 2500 2000 1500 1000 500 0
No Cement
Calcium sulfate
PMMA
Fig. 2. Failure strength of pre- and post-treatment of the No cement, Calcium sulfate and PMMA groups. *Indicates a statistically significant difference, p⬍0.05.
fill. In the study reported here, each vertebral body was filled to 25% of its measured volume during kyphoplasty. The results with PMMA were consistent to that of the aforementioned study. As such, our average posttreatment strength with PMMA was higher than the pretreatment level, whereas posttreatment stiffness was lower at this level of vertebral body filling. Calcium sulfate cement has a much lower native compressive strength and stiffness than that of PMMA. Comparing
both cements, the strength restoration with PMMA (127%) was slightly higher than with CSC (108%), although this was not statistically significant (p⫽.4). Similarly, the stiffness restoration with PMMA (70%) was higher than with CSC (40%), although this did not reach statistical significance (p⫽.1). The same results have been obtained with other cements, eg, calcium phosphate cements, which also have much lower native compressive properties than PMMA [22]. Perhaps, the native compressive property of a cement
Pre Treatment Post Treatment NS
1800
N/mm
* NS
*
1600
NS NS
1400 1200 1000 800 600 400 200 0
No Cement
Calcium Sulfate
PMMA
Fig. 3. Stiffness of pre- and post-treatment of No cement, Calcium sulfate and PMMA groups. * Indicates statistically significant difference, p⬍0.05.
A. Perry et al. / The Spine Journal 5 (2005) 489–493
may not always predict its performance in a vertebral body during kyphoplasty. During cement injection, cement interdigitates into the surrounding cancellous bone. This interdigitation may be an important aspect of biomechanical support. Heini et al. found that the posttreatment vertebroplasty strength and stiffness restoration is inversely proportional to the degree of osteoporosis [23]. In their study, they found a weak correlation (r2⫽.131) between percentage strength restoration and degree of osteoporosis (T-scores). With osteoporosis there is loss in trabecular bone leading to increased intertrabecular spacing. This increased spacing could allow greater cement distribution, that is, interdigitation within the cancellous bone of the vertebral body during kyphoplasty, leading to greater cement effect.
[7]
[8]
[9]
[10]
[11]
[12]
Conclusion Calcium sulfate cement has comparable strength restoration when compared with PMMA for kyphoplasty. Stiffness restoration is lower when compared with PMMA, which may be more desirable in reducing the incident of adjacent level fractures. CSC is bioabsorbable and has a low setting temperature, making it suitable for the addition of growth factors and heat-labile bioactive substances. Further in vivo studies are needed to assess the reabsorption and interaction of CSC with host bone in osteoporotic animal models.
[13]
[14] [15]
[16] [17]
References [1] Riis BJ. Biochemical markers of bone turnover. II: Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;95:17S–21S. [2] Melton LJ 3rd. How many women have osteoporosis now? J Bone Miner Res 1995;10:175–7. [3] Cohen LD. Fractures of the osteoporotic spine. Orthop Clin North Am 1990;21:143–50. [4] Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1999;159:1215–20. [5] Schlaich C, Minne HW, Bruckner T, et al. Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int 1998;8: 261–267. [6] Silverman SL, Minshall ME, Shen W, Harper KD, Xie S. The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from
[18] [19] [20]
[21]
[22]
[23]
493
the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 2001;44:2611–9. Galibert P, Deramond H, Rosat P, Le Gars D. [Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty]. Neurochirurgie 1987;33:166–8. Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J 2000;9:445–50. Belkoff SM, Molloy S. Temperature measurement during polymerization of polymethylmethacrylate cement used for vertebroplasty. Spine 2003;28:1555–9. Berlemann U, Ferguson SJ, Nolte LP, Heini PF. Adjacent vertebral failure after vertebroplasty. A biomechanical investigation. J Bone Joint Surg [Br] 2002;84:748–52. Schildhauer TA, Bennett AP, Wright TM, Lane JM, O’Leary PF. Intravertebral body reconstruction with an injectable in situ-setting carbonated apatite: biomechanical evaluation of a minimally invasive technique. J Orthop Res 1999;17:67–72. Belkoff SM, Mathis JM, Erbe EM, Fenton DC. Biomechanical evaluation of a new bone cement for use in vertebroplasty. Spine 2000;25: 1061–4. Bai B, Jazrawi LM, Kummer FJ, Spivak JM. The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures. Spine 1999;24:1521–6. Watson JT. The use of an injectable bone graft substitute in tibial metaphyseal fractures. Orthopedics 2004;27:s103–7. Kelly CM, Wilkins RM. Treatment of benign bone lesions with an injectable calcium sulfate-based bone graft substitute. Orthopedics 2004;27:s131–5. Peltier LF. The use of plaster of Paris to fill defects in bone. Clin Orthop 1961;21:1–31. Hadjipavlou AG, Simmons JW, Yang J, Nicodemus CL, Esch O, Simmons DJ. Plaster of Paris as an osteoconductive material for interbody vertebral fusion in mature sheep. Spine 2000;25:10–5; discussion 16. Panjabi MM, Takata K, Goel V, et al. Thoracic human vertebrae: quantitative three-dimensional anatomy. Spine 1991;16:888–901. Panjabi MM, Goel V, Oxland T, et al. Human lumbar vertebrae: quantitative three-dimensional anatomy. Spine 1992;17:299–306. Jasper LE, Deramond H, Mathis JM, Belkoff SM. The effect of monomer-to-powder ratio on the material properties of cranioplastic. Bone 1999;25:27S–9S. Molloy S, Mathis JM, Belkoff SM. The effect of vertebral body percentage fill on mechanical behavior during percutaneous vertebroplasty. Spine 2003;28:1549–54. Tomita S, Molloy S, Jasper LE, Abe M, Belkoff SM. Biomechanical comparison of kyphoplasty with different bone cements. Spine 2004; 29:1203–7. Heini PF, Berlemann U, Kaufmann M, Lippuner K, Fankhauser C, van Landuyt P. Augmentation of mechanical properties in osteoporotic vertebral bones: a biomechanical investigation of vertebroplasty efficacy with different bone cements. Eur Spine J 2001;10:164–71.
Biomechanical evaluation of kyphoplasty with calcium sulfate cement in a cadaveric osteoporotic vertebral compression fracture model Andrew Perry, MDa, Andrew Mahar, MScb, Jennifer Massie, MSa, Noemi Arrieta, BSa, Steven Garfin, MDa, Choll Kim, MD, PhDa,* a Veterans Administration and University of California, San Diego, 3350 La Jolla Village Drive, San Diego, CA 92161, USA Biomechanics Laboratory, Children’s Hospital, University of California, San Diego, 3020 Children’s Way, San Diego, CA 92123, USA
b
Received 20 October 2004; accepted 15 March 2005
Abstract
BACKGROUND CONTEXT: Vertebral compression fractures can cause deformity, pain, and disability. Kyphoplasty involves percutaneous insertion of an inflatable balloon tamp into a fractured vertebra followed by injection of polymethylmethacrylate (PMMA) bone cement. PMMA has several disadvantages such as potential thermal necrosis and monomer toxicity. Calcium sulfate cement (CSC) is nontoxic, osteoconductive, and bioabsorbable. PURPOSE: To evaluate the biomechanical performance of CSC for kyphoplasty in cadaveric osteoporotic vertebral bodies. STUDY DESIGN: Destructive biomechanical tests using fresh cadaveric thoracolumbar vertebral bodies. METHODS: Thirty-three vertebral bodies (T9 to L4) from osteoporotic cadaveric spines were disarticulated, stripped of soft tissue, and measured for height and volume. Each vertebral body was compressed at 0.5 mm/s using a hinged plating system on a materials testing machine to create an anterior wedge fracture and reduce the anterior height by 25%. Pretreatment strength and stiffness were measured. Two KyphX inflatable balloon tamps were used to reexpand each vertebral body. After randomization, three groups were created: Group A–no cement; Group B–PMMA; Group C– calcium sulfate cement. Groups B and C were filled with the corresponding cement to 25% of the vertebral body volume. All vertebral bodies were then recompressed by 25% of the post-kyphoplasty anterior height to obtain posttreatment strength and stiffness. RESULTS: Treatment with PMMA restored vertebral strength to 127% of the intact level (4168.2 N⫾2288.7) and stiffness to 70% of the intact level (810.0 N/mm⫾380.6). Treatment with CSC restored strength to 108% of the intact level (3429.6 N⫾2440.7) and stiffness to 46% of the intact level (597.7 N/mm⫾317.5). CSC and PMMA were not significantly different for strength restoration (p⫽.4). Significantly greater strength restoration was obtained with either PMMA or CSC, compared with the control group (p⫽.003 and .03, respectively). Stiffness restoration tended to be greater with PMMA than for CSC, but this difference was not statistically significant (p⫽.1). Both cements had significantly greater stiffness when compared with the control group (p⫽.001 and p⫽.04, respectively). CONCLUSIONS: Use of CSC for kyphoplasty yields similar vertebral body strength and stiffness as compared with PMMA. It may be a useful alternative bone cement for kyphoplasty. Further studies are required to assess the bioabsorption of CSCs after kyphoplasty in vivo. 쑖 2005 Elsevier Inc. All rights reserved.
Keywords:
Calcium sulfate cement; Polymethylmethacrylate; Spine biomechanics; Kyphoplasty; Vertebroplasty; Vertebral compression fracture
FDA device/drug status: not approved for this indication (MIIGX3, Wright Medical Inc., Arlington, TN). Nothing of value received from a commercial entity related to this manuscript.
1529-9430/05/$ – see front matter doi:10.1016/j.spinee.2005.03.011
쑖 2005 Elsevier Inc. All rights reserved.
* Corresponding author. Assistant Professor-Spine Surgery, Department of Orthopaedic Surgery, University of California, San Diego VA Medical Center, La Jolla, California, 3350 La Jolla Village Drive #112D, San Diego, CA 92161. Tel.: (858) 657-8248; fax: (858) 657-8260. E-mail address: [email protected] (C. Kim)
490
A. Perry et al. / The Spine Journal 5 (2005) 489–493
Introduction
Materials and methods
Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of the skeleton, leading to bone fragility and increased fracture risk [1]. Approximately 700,000 vertebral compression fractures occur annually in the United States, mainly secondary to osteoporosis [2,3]. A patient with a single osteoporotic vertebral fracture is at higher risk of sustaining an additional vertebral fracture [4]. Painful osteoporotic vertebral fractures can have significant effects on quality of life and physical function [5]. The mortality rate also increases with the number of vertebrae fractured [6]. Chronic pain and decreased mobility can lead to a depressed mood and loss of independence. Vertebral augmentation via vertebroplasty or kyphoplasty involves the percutaneous injection of bone cement into the fractured vertebral body [7]. Both vertebroplasty and kyphoplasty have been shown to provide rapid pain relief with relatively low complication rates [8]. The most commonly used cement is polymethylmethacrylate (PMMA). Unfortunately, PMMA has several potential disadvantages. PMMA is not bioabsorbable and remains permanently in the body. Its unreacted monomer is toxic, and its high polymerization temperature has resulted in temperature readings as much as 113⬚C on the anterior cortex of treated vertebral bodies in cadaveric studies [9]. The high compressive strength and stiffness of PMMA causes a biomechanical mismatch between treated and untreated vertebral levels which may increase the risk of adjacent-level fractures [10]. Recently, attempts have been made to develop bioabsorbable bone cements that address these potential problems. Cements that have undergone ex vivo biomechanical testing include a carbonated apatite cement (Norian, Cupertino, CA), a bioactive cement (Orthocomp; Orthovita, Malvern, PA), and a calcium phosphate cement (α-BSM; ETEX Corp., Cambridge, MA) [11–13]. All have been shown to possess comparable biomechanical profiles as PMMA in simulated cadaveric vertebral compression fractures. Calcium sulfate cements (CSCs) have been used successfully as bone void fillers for over 100 years [14,15]. The osteoconductive properties of such cements have been known for more than 40 years. These cements have low setting temperatures compatible with living tissue [16]. They encourage vascular in-growth and are replaced by host bone by creeping substitution [17]. Therefore, CSCs possess many favorable properties for potential use in vertebral augmentation. Little is known, however, about the biomechanical performance of these cements for this application. The purpose of the current study was to evaluate the biomechanical profile of a calcium sulfate cement preparation (MIIG X3; Wright Medical Inc., Arlington, TN) for kyphoplasty in a simulated osteoporotic vertebral compression fracture model.
Thirty-three vertebral bodies (T9 to L4) were harvested from two male and three female osteoporotic cadaveric spines (range of age at death, 73 to 89 years). The spines selected had no radiographic evidence of tumors, gross kyphosis, scoliosis, or previous surgery. Each spine was scanned with a Delphi W QDR Series DEXA Scanner (Hologic, Inc., Bedford, MA) to obtain the bone mineral density (BMD) of each vertebra. These BMDs were then compared with the corresponding young normal mean values and each difference expressed as a standard deviation score (ie, T score) to estimate the degree of osteoporosis. Specimens The vertebrae were stripped of soft tissue and the posterior elements removed to facilitate testing. The anterior, posterior, right and left lateral heights of the vertebral bodies were measured with calipers accurate to 0.01 mm (Mattoon MTI Corp., Aurora, IL). Molds of the superior and inferior end plates were made for each vertebral body using an epoxy filler (Bondo; Bondo Corp., Atlanta, GA) to ensure uniform and even loading during compression testing. Vertebral body volumes were calculated using the Archimedean water displacement principle. Volumes obtained in this manner have been shown to be in good agreement with that calculated using vertebral body dimensions obtained from plain films [18,19]. Mechanical testing Each vertebral body was compressed at 0.5 mm per second using a hinged-plated device in a materials testing machine (MTS, Eden Prairie, MN) to create an anterior wedge-fracture and reduce anterior height by 25% of the intact value. Force (N) and displacement (mm) data were recorded at 10 Hz. Stiffness data for each specimen were obtained from the gradient of the load-displacement graph between 500 and 1500 N. Vertebral augmentation The vertebral bodies (T9-L4) were randomly assigned to one of three groups: Group A–No cement; Group B–PMMA (Simplex P; Howmedica Inc., Rutherford, NJ); Group C– calcium sulfate cement (MIIG X3; Wright Medical Inc., Arlington, TN). Kyphoplasty was performed with each balloon tamp (KyphX bone tamp; Kyphon Inc., Sunnyvale, CA) inflated to a maximum of 2 cc or until 220 psi was recorded. Groups B and C were then injected bi-pedicularly with their respective bone cements within the cancellous void to 25% volume fill. For Group B, 40 g of Simplex P powder was combined with approximately 18 g of barium sulfate to create a powder with 32% barium sulfate by dry weight to enhance visualization of the cement under fluoroscopy [20]. PMMA monomer liquid was added to this powder giving a
A. Perry et al. / The Spine Journal 5 (2005) 489–493
monomer to powder ratio of 0.83 mL/g. For CSC, adequate radiographic visualization was achieved by mixing the cement according to the manufacturer’s guidelines of cement preparation without the need for additional barium sulfate. After cement injection, all vertebral bodies were wrapped in saline-soaked gauze and stored at 4⬚C for 24 hours. The anterior, posterior, and lateral heights of each specimen were remeasured and anteroposterior and lateral radiographic images were taken to confirm accurate cement placement. All vertebral bodies were then recompressed by 25% of the new anterior height to obtain posttreatment data, as described previously. Statistical analysis Statistical testing was performed using analysis of variance to compare differences in BMD, T-scores, and vertebral body volumes between groups. A two-way analysis of variance was used to detect the effect of cement type on pretreatment and posttreatment strength and stiffness. Significance was set as p⬍.05. Results No statistically significant differences in mean BMD or T-scores were found between any of the pretreatment groups (p⬍.05). In addition, no significant differences in vertebral body volume or anterior vertebral body heights were found. The average T-score of the vertebral bodies was ⫺2.7 (range ⫺1.5 to ⫺4.5). The average volume of cement injected into each vertebral body was 7.5 cc (range 2.5 cc to 11.75 cc). There was no significant difference in the mean volume of PMMA or CSC that was injected into either of these groups. The average BMD of these specimens was 0.75 g/cm3 (range 0.56 g/cm3 to 0.90 g/cm3). As expected, mean pretreatment strengths of groups A, B, and C were not significantly different from each other (3152.9 N⫾1176.2, 3475.1 N⫾1559.4, and 3239.4 N⫾1204.6, respectively). Similarly, pretreatment stiffness for groups A, B, and C were also not significantly different (1188.3 N⫾369.1, 1176.0 N⫾321.0, and 1478.9N⫾538.4, respectively). CSC showed similar filling characteristics to that in clinical practice with PMMA (Fig. 1).
491
Posttreatment strength and stiffness data are shown in Figures 2 and 3. Treatment with PMMA restored vertebral strength to 127% of the intact level (4168.2 N⫾288.1) and stiffness to 70% of the intact level (810.1 N/mm⫾380.5). Treatment with CSC restored strength to 108% of the intact level (3429.7 N⫾2440.3) and stiffness to 46% of the intact level (598.7 N/mm⫾318.0). There was no statistically significant difference in strength between groups B and C (p⫽.4). Both PMMA and CSC provided significantly higher strength restoration than bone tamp inflation only (Group A), (p⫽.003 and .03, respectively). The average stiffness of Group B (PMMA) was higher than Group C (CSC), but was not statistically significant (p⫽.1). Both PMMA and CSC provided significantly greater stiffness when either was compared with Group A (p⫽.001 and p⫽.04, respectively).
Discussion Although, vertebroplasty and kyphoplasty with PMMA are effective in providing pain relief of vertebral compression fractures, there have been theoretic concerns about potential adverse effects with the use of such acrylic cements. These concerns include the possibility of thermal injury to surrounding tissue and toxicity from the unreacted monomer [9]. The potential for adjacent level fractures as a result of PMMA’s exceedingly high compressive strength and stiffness profile is also of concern. The ideal bone cement should be biodegradable, nontoxic, have a low setting temperature, and have a biomechanical profile closer to that of human bone [10]. In the current study, the biomechanical properties of vertebral bodies treated with kyphoplasty using either CSC or PMMA were compared. Molloy et al. used standard amounts of PMMA cement (2, 4, 6, and 8 mL) for either thoracic (T6-T10), thoracolumbar (T11-L1), or lumbar (L2-L5) vertebrae during vertebroplasty [21]. Linear regression analysis of their results found a weak relation between percentage fill and restored strength and stiffness (r2⫽.21, r2⫽.27 respectively). Full strength restoration was obtained with roughly a 20% fill and full stiffness restoration with a 30%
Fig. 1. Radiograph of L1 vertebral body with calcium sulfate cement. (a) axial view; (b) lateral view.
492
A. Perry et al. / The Spine Journal 5 (2005) 489–493
Pre Treatment Post Treatment 5000
*
4500
N
NS
NS
4000
*
NS
NS
3500 3000 2500 2000 1500 1000 500 0
No Cement
Calcium sulfate
PMMA
Fig. 2. Failure strength of pre- and post-treatment of the No cement, Calcium sulfate and PMMA groups. *Indicates a statistically significant difference, p⬍0.05.
fill. In the study reported here, each vertebral body was filled to 25% of its measured volume during kyphoplasty. The results with PMMA were consistent to that of the aforementioned study. As such, our average posttreatment strength with PMMA was higher than the pretreatment level, whereas posttreatment stiffness was lower at this level of vertebral body filling. Calcium sulfate cement has a much lower native compressive strength and stiffness than that of PMMA. Comparing
both cements, the strength restoration with PMMA (127%) was slightly higher than with CSC (108%), although this was not statistically significant (p⫽.4). Similarly, the stiffness restoration with PMMA (70%) was higher than with CSC (40%), although this did not reach statistical significance (p⫽.1). The same results have been obtained with other cements, eg, calcium phosphate cements, which also have much lower native compressive properties than PMMA [22]. Perhaps, the native compressive property of a cement
Pre Treatment Post Treatment NS
1800
N/mm
* NS
*
1600
NS NS
1400 1200 1000 800 600 400 200 0
No Cement
Calcium Sulfate
PMMA
Fig. 3. Stiffness of pre- and post-treatment of No cement, Calcium sulfate and PMMA groups. * Indicates statistically significant difference, p⬍0.05.
A. Perry et al. / The Spine Journal 5 (2005) 489–493
may not always predict its performance in a vertebral body during kyphoplasty. During cement injection, cement interdigitates into the surrounding cancellous bone. This interdigitation may be an important aspect of biomechanical support. Heini et al. found that the posttreatment vertebroplasty strength and stiffness restoration is inversely proportional to the degree of osteoporosis [23]. In their study, they found a weak correlation (r2⫽.131) between percentage strength restoration and degree of osteoporosis (T-scores). With osteoporosis there is loss in trabecular bone leading to increased intertrabecular spacing. This increased spacing could allow greater cement distribution, that is, interdigitation within the cancellous bone of the vertebral body during kyphoplasty, leading to greater cement effect.
[7]
[8]
[9]
[10]
[11]
[12]
Conclusion Calcium sulfate cement has comparable strength restoration when compared with PMMA for kyphoplasty. Stiffness restoration is lower when compared with PMMA, which may be more desirable in reducing the incident of adjacent level fractures. CSC is bioabsorbable and has a low setting temperature, making it suitable for the addition of growth factors and heat-labile bioactive substances. Further in vivo studies are needed to assess the reabsorption and interaction of CSC with host bone in osteoporotic animal models.
[13]
[14] [15]
[16] [17]
References [1] Riis BJ. Biochemical markers of bone turnover. II: Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;95:17S–21S. [2] Melton LJ 3rd. How many women have osteoporosis now? J Bone Miner Res 1995;10:175–7. [3] Cohen LD. Fractures of the osteoporotic spine. Orthop Clin North Am 1990;21:143–50. [4] Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1999;159:1215–20. [5] Schlaich C, Minne HW, Bruckner T, et al. Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int 1998;8: 261–267. [6] Silverman SL, Minshall ME, Shen W, Harper KD, Xie S. The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from
[18] [19] [20]
[21]
[22]
[23]
493
the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 2001;44:2611–9. Galibert P, Deramond H, Rosat P, Le Gars D. [Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty]. Neurochirurgie 1987;33:166–8. Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J 2000;9:445–50. Belkoff SM, Molloy S. Temperature measurement during polymerization of polymethylmethacrylate cement used for vertebroplasty. Spine 2003;28:1555–9. Berlemann U, Ferguson SJ, Nolte LP, Heini PF. Adjacent vertebral failure after vertebroplasty. A biomechanical investigation. J Bone Joint Surg [Br] 2002;84:748–52. Schildhauer TA, Bennett AP, Wright TM, Lane JM, O’Leary PF. Intravertebral body reconstruction with an injectable in situ-setting carbonated apatite: biomechanical evaluation of a minimally invasive technique. J Orthop Res 1999;17:67–72. Belkoff SM, Mathis JM, Erbe EM, Fenton DC. Biomechanical evaluation of a new bone cement for use in vertebroplasty. Spine 2000;25: 1061–4. Bai B, Jazrawi LM, Kummer FJ, Spivak JM. The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures. Spine 1999;24:1521–6. Watson JT. The use of an injectable bone graft substitute in tibial metaphyseal fractures. Orthopedics 2004;27:s103–7. Kelly CM, Wilkins RM. Treatment of benign bone lesions with an injectable calcium sulfate-based bone graft substitute. Orthopedics 2004;27:s131–5. Peltier LF. The use of plaster of Paris to fill defects in bone. Clin Orthop 1961;21:1–31. Hadjipavlou AG, Simmons JW, Yang J, Nicodemus CL, Esch O, Simmons DJ. Plaster of Paris as an osteoconductive material for interbody vertebral fusion in mature sheep. Spine 2000;25:10–5; discussion 16. Panjabi MM, Takata K, Goel V, et al. Thoracic human vertebrae: quantitative three-dimensional anatomy. Spine 1991;16:888–901. Panjabi MM, Goel V, Oxland T, et al. Human lumbar vertebrae: quantitative three-dimensional anatomy. Spine 1992;17:299–306. Jasper LE, Deramond H, Mathis JM, Belkoff SM. The effect of monomer-to-powder ratio on the material properties of cranioplastic. Bone 1999;25:27S–9S. Molloy S, Mathis JM, Belkoff SM. The effect of vertebral body percentage fill on mechanical behavior during percutaneous vertebroplasty. Spine 2003;28:1549–54. Tomita S, Molloy S, Jasper LE, Abe M, Belkoff SM. Biomechanical comparison of kyphoplasty with different bone cements. Spine 2004; 29:1203–7. Heini PF, Berlemann U, Kaufmann M, Lippuner K, Fankhauser C, van Landuyt P. Augmentation of mechanical properties in osteoporotic vertebral bones: a biomechanical investigation of vertebroplasty efficacy with different bone cements. Eur Spine J 2001;10:164–71.