Sunday, February 07, 1999
Fourteen patients with single level lumbar degenerative disk disease refractory to nonoperative management were randomized 3:1 to receive lumbar interbody arthrodesis with a cylindrical threaded fusion cage filled with recombinant human BMP-2 (rhBMP-2) in a collagen sponge or autogenous iliac crest bone.
At one year, all 11 patients who received rhBMP-2 were judged by three independent radiologists to have solid fusions while only two of the three control patients that received the standard treatment of autogenous iliac crest bone were deemed to be fused.
Scott D. Boden, MD, co-author of scientific paper 41, said "the arthodesis was found to occur more rapidly and reliably than in controls with autogenous bone graft, although the sample size was limited. There were no adverse events related to rhBMP-2." Dr. Boden is director of the Emory Spine Center and associate professor of orthopaedics at Emory University School of Medicine and the VA Medical Center in Atlanta.
Dr. Boden observed that interbody fusion cages have been successful as an adjunct to promote lumbar intervertebral arthodesis in the treatment of painful degenerative disk problems. One of the limitations of these devices is the need for the use of autogenous cancellous bone graft which is associated with additional operative time, cost and morbidity.
Dr. Boden said, "this study provides one of the first demonstrations of consistent and unequivocal osteoinduction by a recombinant growth factor in humans. Until now, study designs have not been able to determine that new bone formation was freely due to the growth factor. In this study, we know it is and have shown that when used at the appropriate dose that we now have the potential to control new bone formation."
The study was a Food and Drug Administration-approved investigational device exemption (IDE) prospective multicenter, nonblinded, randomized, controlled, pilot study design. Patients admitted to the study had lumbar degenerative disk disease as noted by back pain of diskogenic origin with degeneration of the disk confirmed by radiological studies.
Patients were between the ages of 18 and 65 years, had single level symptomatic involvement, had no greater than 25 percent spondylolisthesis and were unresponsive to nonoperative management for at least six months.
Dr. Boden said the mean operative time in the investigational group was approximately half of that in the control group. The difference of 1.4 hours was partly due to the additional time required to harvest iliac crest bone in the control patients. The mean investigational group's hospital stay was 1.3 days less than that of the control group, which was not significant due to the small sample size.
Although the researchers said it is the policy of many journals to require two-year follow-up on clinical trials, they chose to report the preliminary results after one year because the stated goal of radiographic fusion was achieved by six months in all investigational cases and was unchanged at 12 months.
Anterior-posterior, Ferguson, lateral, lateral flexion-extension and computed tomographic (CT) scans with sagittal reconstructions were evaluated. Plain radiographs were evaluated by three blinded radiologists for evidence of fusion defined as less than 5 degrees of angular motion and absence of radiolucent lines covering at least 50 percent of the implant surfaces. CT scans were evaluated blindly by three neuroradiologists and two surgeons for evidence of fusion as defined by the observation of continuous trabecular bone growing through both of the cages.
Clinical outcomes were measured using several instruments, including SF-36, Oswestry Low Back Pain Disability Questionnaire, Neurologic Status and pain medication usage.
In addition to Dr. Boden, the co-authors of the study are Thomas A. Zdeblick, MD, University of Wisconsin School of Medicine, Madison, Wis.; Harvinder S. Sandhu, MD, Hospital for Special Surgery, New York; and Stephen E. Heim, MD, Orthopaedic Associates of DuPage, Carol Stream, Ill.