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


OBJECTIVE
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.


BACKGROUND
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.
Schimandle
J H
JH
Emory Spine Center, Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.
Boden
S D
SD
Hutton
W C
WC
D000818:Animals; D001174:Arthrodesis; D001696:Biomechanical Phenomena; D019485:Bone Morphogenetic Proteins; D016025:Bone Transplantation; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins; D013123:Spinal Fusion; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology
D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D006133:Growth Substances; D011506:Proteins; D011994:Recombinant Proteins; D003094:Collagen