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

Abstract

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 microg rhBMP-7, and 25 mg ICBM + 30 microg 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 microg 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 microg 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.