Evaluation of Radiographic and Patient Outcomes Following Lumbar Spine Fusion Using Demineralized Bone Matrix (DBM) Mixed with Autograft

Proceedings of the NASS 25th Annual Meeting / The Spine Journal 10 (2010) 1S–149S the presence of IL-1, a cytokine known to greatly enhance prostaglandin production, TSE (0.1 mg/ml) further increased PGE2 three times the amount found in the conditioned media of IL-1 treated sample. TSE alone increased COX-2 gene expression three fold, and further stimulated COX2 gene expression in IL-1 treated cells three fold. CONCLUSIONS: TSE at 0.5 mg/ml enhanced PGE2 and PGF2a production in human intervertebral disc cells. This dose of TSE is considered a heavy exposure based on studies using airway epithelial cells. TSE appears to act synergistically with IL-1 to stimulate COX-2 gene expression and PGE-2 production. Because PGE2 and PGF2a have an overall negative impact on disc matrix homeostasis, the findings in this study suggest that cigarette smoking may affect matrix homeostasis or disc healing through the actions of these prostaglandins. Further studies are required to explore the mechanism(s) of how TSE affects COX-2 and prostaglandin production in disc cells. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. doi: 10.1016/j.spinee.2010.07.077

61. Effects of Alendronate on Lumbar Posterolateral Fusion Using Hydroxyapatite in Rabbit Model Ki Hyoung Koo, MD1, Bong Soon Chang, MD2, Jae Hyup Lee, MD3, Choon-Ki Lee, MD2; 1Dongguk University Ilsan Hospital, Goyang City, Republic of Korea; 2Seoul National University Hospital, Seoul, Republic of Korea; 3Seoul Metropolitan Boramae Hospital, Seoul, Republic of Korea BACKGROUND CONTEXT: Alendronate affect bone remodeling and the function of osteoclast. With the increasing use of alendronate in the elderly people, it is important to understand the effects of alendronate on spine fusion. But, there are still some controversies about the effect of alendronate on spinal fusion. There are no studies that show a significant inhibition of spine fusion using porous hydroxyapatite by alendronate. PURPOSE: To study the effect of alendronate on posterolateral lumbar fusion with porous hydroxyapatite in rabbits using clinically relevant dose and high dose. STUDY DESIGN/SETTING: An experimental animal study with randomized, control design in rabbits. PATIENT SAMPLE: Adult New Zealand white rabbits (3–3.5 Kg). OUTCOME MEASURES: Fusion assessments using manual palpation, radiologic study, CT scan and mechanical study were performed. Histological study was also done. METHODS: A total of forty two rabbits underwent posterolateral lumbar spine fusion with porous hydroxyapatite at L4-L5 or L5-L6. Rabbits received saline (control group, fourteen rabbits), alendronate 0.5 mg/kg/week (low dose group, fourteen rabbits), or alendronate 1 mg/kg/week (high dose group, fourteen rabbits) po starting 2 weeks before surgery. Twelve weeks after surgery, all animals were euthanized, and the fusion was assessed by radiograph, manual palpation, CT scan, mechanical testing and histological examination. RESULTS: Two rabbits died during the operation. Three animals died within the first 3 weeks after operation. Another 2 rabbits died during breeding after 4 postoperative weeks, but in autopsy finding, there was no evidence suggesting infection or graft rejection in all dead rabbits. Five new rabbits were added to the study, thus 40 rabbits completed the 12-week course of study. Manual palpation fusion rate showed no notable difference among groups. There were no evidence of dose-dependent and statistically significant difference in fusion rate by CT scan. There was no significant difference in pixel optic density from CT scan among groups. Biomechanical testing showed the tensile strength of the control group was higher than that of treatment groups including low dose group and high dose group (p50.028). The fusion masses of control animals were characterized by a higher predominance of well incorporated, trabeculated bone with prominent marrow element in histological exam. The treatment group showed a higher proportion of woven bone structure, thicker bony trabeculae, and lower bone marrow element.

27S

CONCLUSIONS: There was no statistical difference in fusion rate among groups, but the tensile strength of the treatment groups was significantly lower. Histological examination showed alendronate inhibited bone resorption and remodeling. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. doi: 10.1016/j.spinee.2010.07.078

62. Evaluation of Radiographic and Patient Outcomes Following Lumbar Spine Fusion Using Demineralized Bone Matrix (DBM) Mixed with Autograft Amir H. Fayyazi, MD1, Rudolph Buckley, MD2, Morgan Lorio, MD3, Philip Yuan, MD4, John G. Devine, MD5, Keisha K. Smith, BS6; 1VSAS Orthopaedics, Allentown, PA, USA; 2Hamilton Orthopaedic Surgery and Sports Medicine, Hamilton, NY, USA; 3Neuro Science Solution, Bristol, TN, USA; 4Memorial Orthopaedic Surgical Group, Long Beach, CA, USA; 5 Eisenhower Army Medical Center, Ft. Gordon, GA, USA; 6Exactech, Inc., Gainesville, FL, USA BACKGROUND CONTEXT: There’s been a widespread initiative to mitigate complications and costs associated with the harvest of autograft– mainly iliac crest bone graft (ICBG) – in spinal fusions. A demineralized bone matrix (DBM), when used as an extender of autogenous bone, can aid in minimizing harvesting requirements, thus avoiding the complications associated with ICBG harvest. Despite the wide spread use of DBM, there is little published data supporting its effectiveness. OptecureÒ (Exactech Inc., Gainesville, FL) is a commercially available DBM product. PURPOSE: The purpose of this study is to compare a DBM autograft extender to autograft alone in patients undergoing 1 or 2 level fusion of the lumbar spine. STUDY DESIGN/SETTING: Single Blind, Multi-Center, Randomized, Prospective Clinical Study implemented at 6 US sites. PATIENT SAMPLE: Ninety-four patients were enrolled, 82 randomized, 76 with at least 6 month follow-up. OUTCOME MEASURES: Oswestry Disability Index (ODI), SF-12 patient health surveys, and perceived pain noted on visual analog scales (VAS) were collected preoperatively and at 6-week, 3, 6, 12 and 24-month postoperative time points. Anteroposterior, lateral, flexion, and extension radiographs were obtained. The amount of motion and the quality of the boney fusion was evaluated by an independent radiologist. METHODS: Patients suffering from lumbar stenosis and instability, failing conservative treatment and indicated for primary lumbar fusion, were enrolled into the study. All participating centers obtained IRB approval prior to initiation of study procedures. Patients were randomized to DBM+autograft or autograft only (21 local bone, 10 ICBG, and 5 local bone+ICBG). Surgical approaches include: posterolateral fusion (PLF), anterior lumbar interbody fusion (ALIF), combined posterolateral and interbody fusion (PLF/ILF), and interbody fusion (ILF). Operated levels ranged from L2-S1 and in each case instrumentation was utilized. Fusion was based on presence of continuous bridging trabecular bone in the interbody or posterolateral fusion, !5 degree angular motion, and #3 mm translational motion on the flexion/extension radiographs. Statistical analysis was performed using independent t-test and chi-square. A p-value !0.05 is considered statistically significant. RESULTS: Seventy-six per protocol patients, with minimum 6 month follow-up, were evaluated. Thirty PLF, 18 ALIF, 24 PLF/ILF, and 4 ILF cases were enrolled into the study. There were 49 single level (27 DBM, 22 autograft) and 27 two level (17 DBM, 10 autograft) procedures. Intraoperative complications were noted in 7 patients; dural tear (4), pedicle fracture (1), coagulopathy (1), and unspecified (1). Significant improvement in VAS, ODI, and SF-12 measures were noted in both groups when compared to the pre-operative time point (Table 1). There were no statistically significant differences in clinical outcomes between the treatment groups. At 6

All referenced figures and tables will be available at the Annual Meeting and will be included with the post-meeting online content.

28S

Proceedings of the NASS 25th Annual Meeting / The Spine Journal 10 (2010) 1S–149S

months, 22% of levels were noted to be fused (DBM 22%, autograft 23%), at 1 year, 64% of the levels were noted to be fused (DBM 65%, autograft 63%), and at 2 years, 83% of levels were noted to be fused (DBM 88%, autograft 79%). Similar fusion rates were noted in overall single-level (88%) and two-level (86%) cases at 2 years. One 2-level patient graded as fused was noted to have partial fracture of instrumentation at 12 and 24 months. There were no statistically significant differences in fusion between the DBM and autograft group at 6, 12 and 24 months (p50.974, p50.852 and p50.311, respectively). CONCLUSIONS: The pain and morbidity associated with ICBG harvest site can be avoided by using a DBM graft as a graft extender. The results show that OptecureÒ is an effective adjuvant to autogenous bone in single and 2-level lumbar fusions. FDA DEVICE/DRUG STATUS: Optecure: Approved for this indication. doi: 10.1016/j.spinee.2010.07.079

63. A Nanocomposite Therapy Leads to Robust Spinal Fusion in a Posterolateral Rodent Arthrodesis Model Rehan M. Riaz, Mahesh Polavarapu, Gilbert Roc, Zachary Glicksman, Jason Ghodasra, Erin L. Hsu, PhD, Wellington K. Hsu, MD; Northwestern University, Chicago, IL, USA BACKGROUND CONTEXT: Despite significant advances in both surgical techniques and instrumentation, pseudarthrosis still occurs in 10–15% of patients undergoing spinal fusion procedures. Multiple bone graft substitutes have been utilized to replace iliac crest bone graft, including recombinant BMP-2 (rhBMP-2), which has been shown in clinical trials to elicit successful spinal arthrodesis. However, these alternatives can also be associated with significant clinical complications and a high monetary cost. PURPOSE: This study evaluates a cost-effective combination therapy comprised of a demineralized bone matrix [DBM], nanocrystalline hydroxyapatite, and collagen-based scaffold (TrioMatrix). STUDY DESIGN/SETTING: We utilized a rat spine fusion model to compare the efficacy of TrioMatrix with rhBMP-2 as well as two commercially available DBMs (Grafton and DBX). PATIENT SAMPLE: A total of 34 athymic rats were utilized in this study. OUTCOME MEASURES: Successful fusion was evaluated via several independent measures, including AP radiographs, manual palpation, microCT imaging, and histological analysis. METHODS: Athymic rats underwent a posterolateral intertransverse spinal fusion via a previously published protocol. Animals were randomly assigned to 1 of 5 treatment groups: collagen sponge alone (negative control), rhBMP-2 (positive control), TrioMatrix, Grafton, and DBX. Fusion was assessed via AP radiographs, manual palpation scores, and microCT imaging 8 weeks after implantation. Manual palpation was performed by 3 independent observers based on a three-point scale (Table 1). New bone formation was quantified via microCT, differentiating host bone from the fusion mass. Histological analyses of sagittal cuts through the fusion mass were also performed. RESULTS: Based on manual palpation scores, collagen sponge alone (negative control) had a 0% fusion rate, and rhBMP-2 and TrioMatrix had equivalent fusion rates (100%), which were statistically significantly greater than Grafton and DBX fusion rates (62.5%, Table 1). Interestingly, the microCT quantification showed that use of TrioMatrix led to the greatest amount new bone formation (1070.50 mm3), which was statistically significantly greater than DBX (767.84 mm3), Grafton (435.60 mm3) and BMP (290.88 mm3). Histological, visual, and radiographic analyses demonstrated fusion masses from Triomatrix that were substantially more robust than other treatment groups, including rhBMP-2. CONCLUSIONS: The use of a nanocomposite combination therapy led to equivalent fusion rates compared to rhBMP-2 in this well-established rodent spine fusion model. Furthermore, based on microCT quantification, TrioMatrix led to the greatest volume of bone formation. TrioMatrix represents a promising, cost-effective bone graft substitute that could lead to improved

outcomes with potentially reduced side effects. Given the inflammatory nature of rhBMP-2, future studies are underway to assess the comparative immune response and toxicological impact of TrioMatrix in vivo. FDA DEVICE/DRUG STATUS: TrioMatrix: Investigational/Not approved. doi: 10.1016/j.spinee.2010.07.080

Wednesday, October 6, 2010 5:15–6:15 PM Focused Paper Presentations 5: Interventional 64. A Cost Utility Analysis of Intradiscal Electrothermal Treatment (IDET) Compared with Spinal Fusion Michael P. Grevitt, MD, FRCS1, Brian Freeman, MD, FRCS, FRACS2, John Posnett, PhD3; 1Spinal Unit, Nottingham, United Kingdom; 2Royal Adelaide Hospital, Adelalide, Australia; 3Smith & Nephew Healthcare, York, United Kingdom BACKGROUND CONTEXT: Intradiscal electrothermal therapy (IDET) (Smith & Nephew, London, UK) is a minimally invasive outpatient procedure in which controlled levels of heat are applied directly to the affected disc by means of a navigable intradiscal catheter. There are no data regarding the cost utility of this technique compared with spinal fusion for axial back pain. PURPOSE: To evaluate the cost-effectiveness IDET relative to circumferential lumbar fusion with femoral ring allograft (FRA). STUDY DESIGN/SETTING: Cost-effectiveness analysis; university spinal surgical department. The analysis compares costs in the two years following primary intervention and the gain in patient utility between the immediate pre-operative period and two years post-intervention. PATIENT SAMPLE: Patient-level data were available for patients with discogenic low back pain treated with FRA (n537) in a randomized trial of FRA vs. titanium cage, and for patients recruited to a separate study evaluating the use of IDET (n585). Patients were followed-up for 24 months. The patient groups were similar in age (mean 39.5 yrs (FRA) vs. 42.3 yrs (IDET)) and gender (54% female in both groups). The mean pre-treatment VAS score was significantly higher in the FRA group, indicating greater pain severity (7.0 (FRA) vs. 5.6 (IDET); p50.0016). The mean pre-treatment ODI score was also significantly higher in the FRA group (56.5% (FRA) vs. 48.2% (IDET); p50.0079). Mean duration of symptoms was 73 months for the IDET group and 87 months for the FRA group. There were no significant differences between the groups in SF-36 domain scores, except physical function (p50.004) and mental health (p50.021), both of which were lower in the FRA group, indicating lower quality of life. Baseline utility scores were significantly lower in the FRA group (0.48 vs. 0.52, p50.03) (Table 1 and Fig 1). OUTCOME MEASURES: Oswestry Disability Index, visual analogue scale, quality of life (SF-36), radiographic evaluations, and NHS resource use. METHODS: Health-state utilities were derived for each patient from SF-36 responses collected at baseline (pre-operatively) and at 6, 12 and 24 months post-operatively, by first converting SF-36 to SF-6D and then applying the coefficients of the SF-6D mean model. Quality adjusted life years (QALY) were calculated using the ‘area under the curve’ approach. Cost-effectiveness was measured by the incremental cost per qualityadjusted life year (QALY) gained. RESULTS: Both treatments produced statistically significant improvements in pain, disability and quality of life at the 24-month follow-up. Mean VAS was reduced in both treatment groups between the pre-treatment period and the 24-month follow-up: from 5.6 pre-treatment to 4.1 (IDET; p50.001)), and from 7.2 pre-treatment to 5.2 (FRA; p!0.001)). The difference between the two groups at 24-months was not significant. (p50.0877). Both groups experienced an improvement in low back pain disability (ODI) at 24-months: from 48.2% (‘severe disability’) to 37.4% (‘moderate disability’) in the IDET group (p!0.001), and from 56.5%

All referenced figures and tables will be available at the Annual Meeting and will be included with the post-meeting online content.