Recombinant human bone morphogenetic protein–2 with tapered cages: a prospective, randomized lumbar fusion study

Abstract

Matthew F. Gornet, MD, St. Louis, MO, USA; J. Kenneth Burkus, MD, Columbus, GA, USA; Curtis A. Dickman, MD, Phoenix, AZ, USA; Thomas A. Zdeblick, MD, Madison, WI, USAIntroduction: Anterior lumbar interbody fusion (ALIF) is an effective treatment for patients with symptomatic degenerative disc disease. Results from a small series of patients undergoing ALIF with tapered cages demonstrated that recombinant human bone morphogenetic protein–2 (rhBMP-2) promotes osteoinduction and fusion. To further evaluate the clinical performance of rhBMP-2 with tapered metal cages for lumbar fusion procedures, a larger multicenter study was initiated. This paper reports the clinical and radiographic outcomes at 12 months for this clinical trial.Methods: This prospective, randomized, nonblinded study enrolled 281 patients at 16 investigational sites. Patients were randomized into two groups. The control group was treated with autogenous iliac crest bone graft with a tapered metal cage (LT-CAGE device, Medtronic Sofamor Danek). The rhBMP-2 group received rhBMP-2 on a collagen sponge carrier (InFUSE Bone Graft, Medtronic Sofamor Danek) with the LT-CAGE device.Patient demographics: Preoperatively, all patients had symptomatic, single-level degenerative disc disease and had complaints of disabling low back and/or leg pain. All had symptoms lasting at least 6 months and had failed nonoperative treatments. All patients underwent an ALIF procedure through an open approach. The control group consisted of 136 patients (68 men, 68 women) with an average age of 42.3 years, and the rhBMP-2 group consisted of 145 patients (79 men, 66 women) with an average age of 43.3 years. In the control group, 35.3% used tobacco within 6 months before surgery compared with 32.4% in the rhBMP-2 group. The percentage of patients with pending litigation was 15.4% and 13.1% in the control group and rhBMP-2 group, respectively. The percentage of patients seeking workers compensation was 33.8% for both groups.Clinical and radiographic outcome measurements: Clinical outcomes were assessed using several methods including Oswestry Low Back Pain Disability Questionnaire, Short Form SF-36, neurologic status, work status and back and leg pain questionnaires. Radiographs and computed tomography scans were used to evaluate fusion and were interpreted by two independent, blinded radiologists. A third independent radiologist was used to adjudicate conflicting findings. Fusion criteria included an absence of radiolucent lines covering more than 50% of either cage, translation of 3 mm or less and angulation less than 5 degrees on flexion/extension radiographs and continuous trabecular bone connecting the vertebral bodies.Results: The mean operative time in the rhBMP-2 group was 1.7 hours, and for the control group it was 2.0 hours. The average blood loss in the rhBMP-2 group was 109.3 cc compared with 153.8 cc in the control group. These results were statistically significant (p<.05). The average hospital stay for the rhBMP-2 group was 3.1 days, and for the control group it was 3.3 days. Follow-up rates exceeded 97% for both groups at 12 months. There were no unanticipated device-related adverse events in either treatment group.Clinical and radiographic outcomes: Pain associated with activities was measured by the Oswestry Disability Questionnaire. In the rhBMP-2 group, 76.9% of patients showed an improvement of at least 15 points in their disability scores at 12 months after surgery. This compared favorably with 75.8% of patients in the control group. At 6 months after surgery, 97% of patients in the rhBMP-2 group showed evidence of interbody fusion compared with 95.8% in the control group. At 12 months, 96.9% of patients in the rhBMP-2 group were fused compared with 92.5% in the control group. The overall success rate (defined as fusion, neurological and Oswestry success, no second surgery failures and no serious device-related adverse events) was statistically equivalent between the two treatment groups at 12 months.Discussion: Results from this study of ALIF procedures with tapered cages revealed reduced operative times, less blood loss and shorter hospital stays with the use of rhBMP-2 compared with autograft. These data demonstrate potential improvements in lumbar fusion procedures that may positively impact surgery and hospital efficiencies. Patients receiving rhBMP-2 also had higher fusion rates than patients who were treated with autograft. Clinical outcomes comparing autograft with rhBMP-2 were similar for both patient groups in this study. Overall results show that the use of rhBMP-2 can eliminate the need for harvesting iliac crest for successful lumbar fusions.Conclusion: The combination of rhBMP-2 with a tapered cage has demonstrated itself as a promising alternative of facilitating anterior intervertebral spinal fusion, decreasing pain and improving clinical outcomes.