Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis.

BACKGROUND: Previous studies have demonstrated the ability of recombinant human bone morphogenetic protein to achieve a solid fusion in anterior lumbar interbody arthrodesis. The purpose of this study was to compare iliac crest bone graft and recombinant human bone morphogenetic protein-2, combined with a carrier consisting of bovine collagen and beta-tricalcium phosphate-hydroxyapatite to create a compression-resistant matrix, for instrumented single-level posterolateral arthrodesis. METHODS: Four hundred and sixty-three patients with symptomatic single-level lumbosacral degenerative disease with no greater than grade-1 spondylolisthesis were treated with single-level instrumented posterolateral arthrodesis through an open midline approach. Patients were randomly assigned to either the recombinant human bone morphogenetic protein-2 matrix group (239 patients) or the autogenous iliac crest bone-graft group (224 patients). The Oswestry Disability Index, Short Form-36, and back and leg pain scores were determined preoperatively and at 1.5, three, six, twelve, and twenty-four months postoperatively. Radiographs and computed tomography scans were made at six, twelve, and twenty-four months postoperatively to evaluate for fusion. RESULTS: The mean operative time and mean blood loss in the recombinant human bone morphogenetic protein-2 matrix group (2.5 hours and 343.1 mL, respectively) were significantly less than those in the iliac crest bone-graft group (2.9 hours and 448.6 mL). Both groups showed similar improvements in clinical outcomes and reduced pain. At twenty-four months, 60% of the iliac crest bone-graft group reported donor-site pain. At twenty-four months, fusion was evident in 96% of the patients in the recombinant human bone morphogenetic protein-2 matrix group compared with 89% in the iliac crest bone-graft group (p = 0.014). There was a significant difference (p = 0.011) in the rate of failures because of nonunion (eighteen patients with an iliac crest bone graft compared with six patients with the recombinant human bone morphogenetic protein-2 matrix). Also, the number of patients requiring second surgeries was significantly higher in the iliac crest bone-graft group (thirty-six patients) compared with the recombinant human bone morphogenetic protein-2 matrix group (twenty patients) (p = 0.015). CONCLUSIONS: The use of recombinant human bone morphogenetic protein-2 in instrumented posterolateral lumbar arthrodesis decreases operative time and blood loss and produces earlier and higher fusion rates than does iliac crest bone graft. Clinical outcomes are similar to those with iliac crest bone graft. Thus, the need for harvesting iliac crest bone is eliminated along with the morbidities associated with the harvest procedure.

Two-year fusion and clinical outcomes in 224 patients treated with a single-level instrumented posterolateral fusion with iliac crest bone graft.

BACKGROUND CONTEXT: Reported fusion rates for spine fusions using iliac crest bone graft (ICBG) vary between 40% and 100% because of different fusion techniques, patient comorbidity, diagnosis and assessment criteria. PURPOSE: We report two-year results of single-level instrumented posterolateral fusions evaluated with radiographs, fine-cut computed tomography (CT) scans with reconstructions and outcome measures. STUDY DESIGN/ SETTING: Retrospective analysis of data from a prospective multicenter randomized clinical controlled trial. PATIENT SAMPLE: Patients with various degenerative diagnoses enrolled in the control arm of a Food and Drug Administration (FDA)-regulated, multicenter trial of single-level decompression and posterolateral fusion for degenerative lumbar disease. OUTCOME MEASURES: Short Form-36 (SF-36), Oswestry Disability Index (ODI), Numeric Rating Scales (0-20) for back, leg, and graft site pain, CT scans, anteroposterior and lateral flexion/extension radiographs. METHODS: Patients enrolled in an FDA-regulated, multicenter trial at 29 sites with degenerative lumbar disease treated with single-level instrumented posterolateral fusion with ICBG were included in the analysis. Demographic and surgical data were collected. Clinical outcomes were followed using standard metrics. Fusion was assessed by independent radiologists at 6, 12, and 24 months postoperatively. Two fusion criteria were compared: anteroposterior and flexion/extension radiographs to assess motion and bridging bone, with CT scans as needed to confirm bridging bone; and CT scan assessment for bridging bone only. RESULTS: One hundred ninety-four of 224 subjects (86.6%) completed the study. The mean operative time was 2.9 hours with a blood loss of 448.6 mL. The average graft volume was 36.3 mL. There were 21 (9.4%) wound infections, 18 (8.0%) incidental durotomies, 3 (1.3%) implant displacements, 2 (0.9%) malpositioned implants, and 17 (7.6%) graft-related complications. Twenty-seven patients (13.9%) required reoperation, the majority for nonunions. Fusion rates based on radiographs with selective CTs at 6, 12, and 24 months were 65.3%, 82.5%, and 89.3%, respectively. Fusion rates based on bridging bone on CT scans were 56.1%, 71.5%, 83.9%, respectively. Two-year improvement for all outcome measures was significant (p<.001)-ODI 25.3, SF-36 Physical Component Score (PCS) 12.2, back pain 7.9, and leg pain 7.1. Two years postoperatively, 60% of patients complained of graft site pain (mean pain score=8.5). CONCLUSION: In a large series of patients who had primary single-level instrumented posterolateral fusion with ICBG, evidence of bridging bone on fine-cut CT scans improved with time to 83.9% at 24 months. Significant improvement from baseline was noted in all clinical outcome measures at all time intervals with 75% achieving minimum clinically important difference (MCID) for ODI and 66% achieving MCID for SF-36 PCS.

The effect of arthrodesis, implant stiffness, and time on the canine lumbar spine.

STUDY DESIGN: Canine posterior lumbar instrumentation and fusion. OBJECTIVES: To study effects of implant rod size and time on the stiffness of related spine construct elements. SUMMARY OF BACKGROUND DATA: The ideal stiffness of posterior spinal implants to successfully treat clinical instability or deformity with minimal side effects is unknown. METHODS: Twenty-six canines were divided into 7 groups: control, and 6 or 12-month survival after sham or lumbar L3-5 arthrodesis (facet, posterior, and posterolateral) with either 4.76 or 6.35 mm diameter rod-pedicle screw instrumentation. Axial flexion-compression stiffness of the L3-5 segment components and axial compression stiffness of the bypassed and adjacent anterior column elements were measured. RESULTS: Posterior instrumentation initially increased flexion-compression stiffness of the L3-5 segment more than the intrinsic stiffness of the implant due to control of spinal column flexion buckling. Sham operation did likewise, apparently by posterior scar tissue tethering. The percent contribution of the implant construct to instrumented segment stiffness was significantly less at 6 months without further change from 6 to 12 months; 14% and 22% for 4.76 and 6.35 mm rod constructs, respectively. Spinal column as well as posterior column stiffness after fusion was independent of rod size at 6 months and increased at 12 months in only the 4.76 mm rod group. Bypassed L4 vertebral body stiffness decreased significantly at 6 months, was not rod size dependent and changed little between 6 and 12 months. Bypassed disk stiffness responded in a biphasic manner, apparently increasing at 6 months with significant decrease from 6 to 12 months. Adjacent disk compression stiffness progressively decreased over time independent of rod size, also decreasing after sham operation. CONCLUSIONS: Both rod sizes were associated with 100% fusion and produced similar changes in bypassed bone and disks, and adjacent disks. There was delayed fusion stress shielding by 6.35 mm rod constructs.

The efficacy of rhBMP-2 for posterolateral lumbar fusion in smokers.

STUDY DESIGN: Retrospective review of prospectively collected data, as part of an IRB-approved, FDA-regulated, randomized, nonblinded IDE trial of rhBMP-2 matrix for lumbar spinal fusion. OBJECTIVES: The purpose of this study is to examine the influence of smoking on fusion rate and outcome in a large series of patients treated with an rhBMP-2 matrix (AMPLIFY) or iliac crest bone graft as part of a randomized IDE trial for single-level lumbar fusion. SUMMARY OF BACKGROUND DATA: Preclinical studies suggest that bone morphogenetic proteins (BMPs) are able to reverse the negative influence of nicotine on fusion healing in animal models. It remains unclear if a similar benefit will be seen in humans, and if so, what formulation and amount of BMP will be required to achieve that improvement. METHODS: We reviewed the clinical and radiographic records of 148 patients who underwent single-level instrumented lumbar fusion at three spine centers as part of an ongoing FDA-regulated IDE trial. Clinical outcome measures included Oswestry Disability Index, SF-36, back, and leg pain scores. Radiographic measures were plain radiographs with flexion-extension views and fine cut computed tomography scans with sagittal and coronal reconstruction. Fusion success was determined by independent radiologist readings. RESULTS: At 2 years postoperatively, solid fusion was demonstrated in all 55 nonsmokers in the rhBMP-2 group (100%). Successful fusion was seen in 20 of 21 smokers in the rhBMP-2 group (95.2%). Fusion was achieved in 48 of 51 nonsmokers in the iliac crest bone graft (ICBG) group (94.1%), but only 16 of 21 smokers (76.2%) in the ICBG group. CONCLUSIONS: The results of this study suggest that rhBMP-2 may enhance fusion rate in cigarette smokers undergoing single-level instrumented posterolateral lumbar fusion. Despite the improvement in fusion rate with rhBMP-2, clinical outcomes measures were still adversely affected in smokers.