The effect of osteogenic protein-1 instrumented and noninstrumented lumbar fusion in rabbits

Abstract

Louis G. Jenis, MD, Boston, MA, USA; Donna Wheeler, PhD, Fort Collins, CO, USA; Steven Parazin, MD, Raymond J. Connolly, PhD, Hubert Wolfe, MD, Boston, MA, USAIntroduction: The goal of lumbar spinal fusion is to attain solid arthrodesis. Nonunion remains a significant challenge and may lead to added morbidity and requirements for additional surgeries. The goal of the study is to evaluate the effect of osteogenic protein-1 (OP-1: also known as bone morphogenetic protein–7 [BMP-7]) in a rabbit instrumented and noninstrumented lumbar fusion model as a bone graft substitute. The current study was designed to determine whether the effect of OP-1 could be enhanced in a more rigid environment.Methods: The outcome of intertransverse process fusion with OP-1 versus iliac crest autograft in the presence and absence of rigid fixation was studied. Animal care research committee approval was obtained. Forty-eight adult male New Zealand white rabbits were divided into four groups of 12 animals: 1) control animals: in situ posterolateral arthrodesis L5–L6 using autogenous bone graft; 2) fixation group: posterolateral arthrodesis L5–L6 with autogenous bone graft and interspinous wiring supplemented with polymethylmethacrylate (PMMA) to simulate rigid fixation; 3) OP-1 group: undergo in situ posterolateral arthrodesis L5–L6 using OP-1 and 4) combined OP-1 and rigid fixation. Animals were sacrificed at 3 and 12 weeks after surgery and lumbar spines harvested. Each specimen was evaluated with computed tomographic axial, including reconstructed sagittal and coronal, images to assess fusion. Computed tomographic data were analyzed for four specimens within each treatment group and at each time interval. Fusion was classified by grade: 0) pseudarthrosis; 1) traversing bone lacking bridging and 2) solid fusion. In addition, decalcified histologic analysis of the intertransverse process region was performed with emphasis on cellular activity and bone formation. Gene expression within the fusion mass was performed by RT-polymerase chain reaction techniques. Type 1 collagen, osteocalcin, osteopontin and alkaline phosphatase activity was evaluated.Results: At 3 weeks, autograft within fixation specimens showed 0% grade 2, 100% grade 1 and 0% grade 0 fusion by CT imaging. OP-1–treated animals at 3 weeks showed 0% grade 2, 50% grade 1 and 50% grade 0 fusion. At this early time interval radiographic bone formation was noted in half of the rabbits, although complete arthrodesis was not evident. At 3 months, autograft animals showed 0% grade 2, 75% grade 1 and 25% grade 0 fusion. OP-1 animals showed 100% grade 2 solid fusions by this late time interval. Autograft and OP-1 treated animals with fixation at 3 weeks revealed identical 25% grade 2, 75% grade 1 and 0% grade 0 fusion. Three–month specimens of autograft-fixation exhibited 50% grade 2 and 50% grade 1 fusion, whereas OP-1 fixation achieved 100% grade 2 fusion. Histologic and gene expression results will also be presented.Discussion: This study demonstrates that OP-1 is an effective osteoinductive agent in lumbar intertransverse process fusion at both early and late time intervals. Spinal rigid fixation may potentiate the effect of OP-1 as evidenced by one of four animals showing arthrodesis by 3 weeks. OP-1 is effective as a bone graft substitute, as evidenced by radiographic, histologic and molecular data.