Experimental spinal fusion with recombinant human bone morphogenetic protein-2.

STUDY
DESIGN: Lumbar intertransverse process arthrodesis using recombinant human bone morphogenetic protein-2 was performed in a previously established rabbit model for posterolateral spinal fusion and compared with fusions achieved using autogenous bone graft.
OBJECTIVES: To qualitatively compare different recombinant human bone morphogenetic protein-2 dosages and carriers and to determine the efficacy of recombinant human bone morphogenetic protein-2 as a bone graft substitute to produce lumbar intertransverse process fusion in a validated rabbit model for posterolateral spinal fusion. SUMMARY OF BACKGROUND DATA: Autogenous bone was considered the most successful bone graft material used for spinal arthrodesis. Problems with its use may occur in 25-30% of patients and prompted the search for and investigation of bone graft substitutes and osteoinductive growth factors, such as bone morphogenetic proteins. Recombinant human bone morphogenetic protein-2 was used successfully in orthotopic sites to generate bone in animal mandibular and long bone defect models.
METHODS: Posterolateral intertransverse process arthrodeses were performed at L5-L6 in 56 rabbits using recombinant human 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 dosages and carriers or 4 weeks later to compare the efficacy of recombinant human bone morphogenetic protein-2 in achieving spinal fusion compared with using autogenous bone graft. Inspection, manual palpation, radiography, histology, and biomechanic testing were used to assess the fusion.
RESULTS: All rabbits implanted with recombinant human bone morphogenetic protein-2 achieved solid spinal fusion by manual palpation and were fused radiographically, whereas only 42% of the autograft control fusions were solid. More mature fusions with greater trabecular bone formation were shown radiographically and histologically in rabbits implanted with the high-dose recombinant human bone morphogenetic protein-2 than with the low-dose recombinant human bone morphogenetic protein-2. Fusions achieved using recombinant human bone morphogenetic protein-2 delivered in the collagen carrier were more remodeled and homogeneous compared with using recombinant human bone morphogenetic protein-2 delivered in autograft +/- collagen carrier. Fusions achieved with recombinant human bone morphogenetic protein-2 were biomechanically stronger and stiffer than fusions achieved using autogenous bone graft.
CONCLUSIONS: Recombinant human bone morphogenetic protein-2 successfully and reliably achieved lumbar intertransverse process fusion in a validated rabbit model for posterolateral spinal fusion. Radiographically and histologically, greater and more rapid bone formation, consolidation, and remodeling were shown with recombinant human bone morphogenetic protein-2 compared with autogenous bone graft. Fusions achieved with recombinant human bone morphogenetic protein-2 were biomechanically stronger and stiffer than autograft fusions.