EXPERIMENTAL SPINAL-FUSION WITH RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2

Design, Lumbar intertransverse process arthrodesis using recombinant h uman bone morphogenetic protein-2 was performed in a previously establ ished rabbit model for posterolateral spinal fusion and compared with fusions achieved using autogenous bone graft. Objectives. To qualitati vely compare different recombinant human bone morphogenetic protein-2 dosages and carriers and to determine the efficacy of recombinant huma n bone morphogenetic protein-2 as a bone graft substitute to produce l umbar intertransverse process fusion in a validated rabbit model for p osterolateral spinal fusion. Summary of Background Data. Autogenous bo ne was considered the most successful bone graft material used for spi nal arthrodesis. Problems with its use may occur in 25-30% of patients and prompted the search for and investigation of bone graft substitut es and osteoinductive growth factors, such as bone morphogenetic prote ins. Recombinant human bone morphogenetic protein-2 was used successfu lly in orthotopic sites to generate bone in animal mandibular and long bone defect models. Methods. Posterolateral intertransverse process a rthrodeses were performed at L5-L6 in 56 rabbits using recombinant hum an bone morphogenetic protein-2 or autogenous bone graft. Rabbits were killed either 5 weeks later to qualitatively compare fusions achieved using different recombinant human bone morphogenetic protein-2 dosage s and carriers or 4 weeks later to compare the efficacy of recombinant human bone morphogenetic protein-2 in achieving spinal fusion compare d with using autogenous bone graft. Inspection, manual palpation, radi ography, histology, and biomechanic testing were used to assess the fu sion. Results, All rabbits implanted with recombinant human bone morph ogenetic protein-2 achieved solid spinal fusion by manual palpation an d were fused radiographically, whereas only 42% of the autograft contr ol fusions were solid. More mature fusions with greater trabecular bon e formation were shown radiographically and histologically in rabbits implanted with the high-dose recombinant human bone morphogenetic prot ein-2 than with the low-dose recombinant human bone morphogenetic prot ein-2. Fusions achieved using recombinant human bone morphogenetic pro tein-2 delivered in the collagen carrier were more remodeled and homog eneous compared with using recombinant human bone morphogenetic protei n-2 delivered in autograft +/- collagen carrier. Fusions achieved with recombinant human bone morphogenetic protein-2 were biomechanically s tronger and stiffer than fusions achieved using autogenous bone graft. Conclusions. Recombinant human bone morphogenetic protein-2 successfu lly and reliably achieved lumbar intertransverse process fusion in a v alidated rabbit model for posterolateral spinal fusion. Radiographical ly and histologically, greater and more rapid bone formation, consolid ation, and remodeling were shown with recombinant human bone morphogen etic protein-2 compared with autogenous bone graft. Fusions achieved w ith recombinant human bone morphogenetic protein-2 were biomechanicall y stronger and stiffer than autograft fusions.