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

Abstract

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.

Keywords: Bone morphogenetic protein; Osteoporosis; Rat; Spine.