Estrogen-dependent actions of bone morphogenetic protein-7 on spine fusion in rats

Study Design. Intertransverse process spinal fusion using recombinant human bone morphogenetic protein-7 (rhBMP-7) was performed in intact and ovariectomized female rats. Objectives. To examine fusion rates in intact and ovariectomized female rats using rhBMP-7 to determine if spine fusion is dependent on estrogen status. Summary of Background Data. Rat spinal fusion has been established as a consistent, efficient model for posterolateral intertransverse process fusion. Previous experiments have confirmed the efficacy of pellets containing the carrier, insoluble collagen bone matrix (ICBM), and rhBMP-7 to augment intertransverse process single level fusion in a rat model. Studying these implications in an osteoporosis model is of clinical value because there are many patients undergoing spinal fusion surgery that have osteoporotic bone disease, and there is a steady increase in this group of patients. Methods. A total of 15 ovariectomized and 15 intact Sprague-Dawley female rats were randomly assigned to groups receiving 25 mg ICBM alone, 25 mg ICBM + 10 μg rhBMP-7, and 25 mg ICBM + 30 μg rhBMP-7. Spinal fusion was evaluated by manual motion testing at each lumbar segment, radiographic evaluation using the Lenke grading system, and histology. Results. Ovariectomized and intact rats receiving 25 mg carrier ICBM alone did not show spinal fusion. With 25 mg ICBM + 10 μg rhBMP-7, there was not a significant difference in fusion rates between intact and ovariectomized rats (P = 0.63). Ovariectomized rats receiving 25 mg ICBM + 30 μg rhBMP-7 showed significantly lower fusion rates than intact rats (P = 0.013). Conclusion. These data suggest that spinal fusion using rhBMP-7 is estrogen-dependent in rats. At the dosages used, rhBMP-7 was unable to overcome the inhibitory effects of estrogen deficiency on spinal fusion.