EFFECTIVE DOSES OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 IN EXPERIMENTAL SPINAL-FUSION

Study Design. Nineteen dogs underwent L4-L5 intertransverse process fu sions with either 58 mu g, 115 mu g, 230 mu g, 460 mu g, or 920 mu g o f recombinant human bone morphogenetic protein-2 carried by a polylact ic acid polymer. A previous study (12 dogs) compared 2300 mu g of reco mbinant human bone morphogenetic protein-2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared. Objectives. To characterize the dose-response relationship of recombin ant human bone morphogenetic protein-2 in a spinal fusion model. Summa ry of Background Data. Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein-2, are effective in verte brate diaphyseal defect and spinal fusion models. It is hypothesized t hat the quality of spinal fusion produced with recombinant human bone morphogenetic protein-2, above a threshold dose, does not change with increasing amounts of inductive protein. Methods. After decortication of the posterior elements, the designated implants were placed along t he intertransverse process space bilaterally. The fusion sites were ev aluated after 3 months by computed tomography, manual testing, mechani cal testing, and histologic analysis. Results. As in the study using 2 300 mu g of recombinant human bone morphogenetic protein-2, implantati on of 58-920 mu g of recombinant human bone morphogenetic protein-2 su ccessfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carri er alone. The cross-sectional area of the fusion mass and mechanical s tiffness of the L4-L5 intersegment were not dose-dependent. Histologic al findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the vo lume of the fusion mass. Conclusions. No mechanical, radiographic, or histological differences in the quality of intertransverse process fus ion resulted from a 40-fold variation in dose of recombinant human bon e morphogenetic protein-2.