Manipulation of anabolic and catabolic responses with bone morphogenetic protein and zoledronic acid in a rat spinal fusion model.

Abstract

Bone fusion involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the surgical site. It has been reported that systemically administering a single dose of zoledronic acid (ZA) at the optimal time increases the strength of the bone morphogenetic protein (BMP)-mediated callus. In the present study, we aimed to investigate the effect of BMP-2 and ZA in a rat spinal model. Sixty-seven rats were divided into 6 groups: group I (n=11) animals were implanted with a carrier alone, group II (n=12) animals were implanted with a carrier and a subcutaneous injection of ZA was administered 2weeks after surgery, group III (n=12) animals were implanted with a carrier containing 1μg of rhBMP-2, group IV (n=12) animals were implanted with a carrier containing 1μg of rhBMP-2 and a subcutaneous injection of ZA was administered 2weeks after surgery, group V (n=10) animals were implanted with a carrier containing 3μg of rhBMP-2, and group VI (n=10) animals were implanted with a carrier containing 3μg of rhBMP-2 and a subcutaneous injection of ZA was administered 2weeks after surgery. The rats were euthanized after 6weeks, and their spines were explanted and assessed by manual palpation, radiography, high-resolution micro-computerized tomography (micro-CT), and histologic analysis. The fusion rates in group VI (60%) were considerably higher than those in the groups I (0%), II (0%), III (12.5%), IV (20.8%), and V (35%), (P<0.05). Additionally, the radiographic scores of group VI were higher than those in the other groups, (P<0.05). In micro-CT analysis, the tissue and bone volumes of the callus were significantly higher in group VI than those in the other groups, (P<0.05). The trabecular number was significantly higher and the trabecular spacing was significantly lower in group VI than those in the other groups, (P<0.05). The combination of rhBMP-2 and ZA administered systemically as a single dose at the optimal time was efficacious in our rat spinal fusion model. Our results suggest that this combination facilitates spinal fusion and has potential clinical application.