BMP-2 induced early bone formation in spine fusion using rat ovariectomy osteoporosis model

摘要

Background context Bone morphogenetic proteins (BMPs) enhance bone formation. Numerous animal studies have established that BMPs can augment spinal fusion. However, there is a lack of data on the effect of BMP-2 on spinal fusion in the osteoporotic spine. Purpose To investigate whether recombinant human BMP-2 (rhBMP-2) enhances spine fusion in an ovariectomized rat model. Study design In vivo animal study. Methods Female Sprague-Dawley rats (n=60) were ovariectomized or sham operated and randomized into three groups: Sham (sham operated+fusion), ovariectomy (OVX) (OVX+fusion), and BMP (OVX+fusion+BMP-2). Six weeks after ovariectomy, unilateral lumbar spine fusion was performed using autologous iliac bone with/without rhBMP-2 delivered on a collagen matrix. For each group, gene expression and histology were evaluated at 3 and 6 weeks after fusion, and bone parameters were measured by microcomputed tomography at 3, 6, 9, and 12 weeks. Results Real-time reverse-transcription polymerase chain reaction at 3 weeks showed markedly increased expression of osteoblast-related markers (namely alkaline phosphatase, osteocalcin, Runx2, Smad1, and Smad5) in the BMP group compared with the other groups (p=.0005,.0005,.003,.009 and.012, respectively). Although the Sham and OVX groups showed both sparse and compacted bones between transverse processes at 6 weeks, the BMP group had a significantly larger bone mass within the fusion bed at 3 weeks and later. All rats in the BMP group had bridging bone at 3 weeks; at 12 weeks, bridging bones in the Sham and OVX groups were about 50% and 25%, respectively, of that in the BMP group. Conclusions Recombinant human BMP-2 enhances spinal fusion in OVX rats and acts during early bone formation. Therapeutic BMP-2 may therefore improve the outcome of spinal fusion in the osteoporotic patient.