THE USE OF AN OSTEOINDUCTIVE GROWTH-FACTOR FOR LUMBAR SPINAL-FUSION .2. STUDY OF DOSE, CARRIER, AND SPECIES

Study Design. Efficacy of a bovine-derived osteoinductive growth facto r was studied in a rabbit model and in a nonhuman primate model of pos terolateral lumbar spinal fusion. Objectives. To determine the minimum effective dose of growth factor and the Influence of different carrie r material on the outcome of intertransverse process lumbar fusion. Su mmary of Background Data. Bone morphogenetic proteins and related grow th factors are becoming increasingly available in purified extract or genetically engineered forms and are capable of inducing new bone form ation in vivo. Osteoinductive growth factors to enhance lumbar spinal fusion have not been well studied in models of posterolateral intertra nsverse process:fusion. Because of the diminished potential of bone re generation in primates (including humans) compared with phylogenetical ly lower animals, extrapolations regarding dose and efficacy cannot be made directly from results obtained in experiments performed on phylo genetically lower animals. Experiments on nonhuman primates are a crit ical step before attempting to use these growth factors in humans. Met hods. One hundred fifteen adult New Zealand white rabbits and 10 adult rhesus macaques underwent single level posterolateral intertransverse process lumbar spinal arthrodesis to evaluate different doses and car rier materials fora bovine-derived osteoinductive bone protein extract , Rabbit fusion masses were evaluated 5 weeks after arthrodesis by man ual palpation, radiography, biomechanical testing, and light microscop y. Monkey fusion masses were evaluated 12 weeks after arthrodesis by r adiography and light microscopy. Results. Successful posterolateral in tertransverse process spinal fusions were achieved in the rabbit model using an osteoinductive growth factor with three different carriers ( autogenous iliac bone, demineralized allogeneic bone matrix, and natur al coral). There was a dose-dependent response to the osteoinductive g rowth factor in the rabbit model, indicating that a threshold must be overcome before bone formation is induced. The methodology for biologi c enhancement of spinal fusion developed in the rabbit model was trans ferred successfully to the rhesus monkey, where the use of the osteoin ductive growth factor with a demineralized bone matrix carrier resulte d in spinal fusion in 12 weeks. Conclusions. These experiments provide an essential building block in the understanding of the biology of sp inal fusion and the use of osteoinductive growth factors to enhance a posterolateral intertransverse process spinal fusion. The achievement of posterolateral spinal fusion in the rhesus monkey using an osteoind uctive growth factor is a significant step toward the biologic enhance ment of spinal fusion in humans.