3:51 Recombinant human bone morphogenic protein–2 for posterolateral spine fusion: a prospective/randomized clinical trial

Abstract

Purpose of study: To determine if the dose and carrier for recombinant human bone morphogenetic protein–2 (rhBMP-2), which was successful in rhesus monkeys, could induce consistent radiographic spine fusions in humans.Methods used: Twenty-five patients undergoing lumbar arthrodesis were randomized (1:2:2 ratio): 1) autograft/TSRH pedicle screw instrumentation (n=5); 2) rhBMP-2/TSRH (n=11) and 3) rhBMP-2 only without internal fixation (n=9). The carrier was 60% hydroxyapatite/40% tricalcium phosphate granules (10 cm3 per side) with 20 mg rhBMP-2 per side. Patients had single-level disc degeneration, Grade I or less spondylolisthesis, mechanical low back pain with or without leg pain and failed at least 6 months of nonoperative treatment. The primary outcome was radiographic fusion measured by two independent/masked radiologists, as defined by evidence of continuous bridging trabecular bone as well as less than 3 mm translation and less than 5 degrees angular motion on flexion/extension films. Computed tomography scans were used to assess fusion mass continuity if there was uncertainly on the plain films. Secondary outcome measures included Oswestry and SF-36.of findings: All 25 patients were available for follow-up (mean, 17 months; range, 12 to 27 months). The radiographic fusion rate was 40% (2 of 5) in the autograft/TSRH group and 100% (20 of 20, p=.05) with rhBMP-2 with or without TSRH internal fixation. A statistically significant improvement in Oswestry score was seen at 6 weeks in the rhBMP-2–only group (−17.6, p=.009) and at 3 months in the rhBMP-2/TSRH group (−17.0, p=.003) but not until 6 months in the autograft/TSRH group (−17.3, p=.041). At final follow-up, Oswestry improvement was greatest in the rhBMP-2–only group (−28.7, p<.001). SF-36 Pain Index and PCS subscales showed similar changes.Relationship between findings and existing knowledge: This represents the first prospective, randomized clinical trial using a recombinant BMP for posterolateral spine fusion without autogenous bone graft. The radiographic fusion rates obtained appear to be higher than the control group in the study and most historical controls published in the literature for this diagnosis.Overall significance of findings: Recombinant human BMP-2 with the biphasic calcium phosphate granules consistently induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients with not greater than Grade I spondylolisthesis. There was a statistically greater and quicker improvement in patient-derived clinical outcome measures in the rhBMP-2 groups. These findings provide hope that bone graft harvest and its associated morbidity may not be needed and the clinical results may be at least as good or better than those with autogenous iliac crest bone.Disclosures: Device or drug: rhBMP-2. Status: investigational. Device or drug: BCP Ceramic Granules. Status: investigational. Device or drug: TSHR pedicle screws/rods. Status: approved.Conflict of interest: Scott D. Boden, grant research support; Scott D. Boden and John G. Heller, consultants Medtronic Sofamor Danek.