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Abstract
Introduction The present experiment is undertaken to determine if a single dose addition of OP-1 device (rhBMP-7 and TCP-CMC) will enhance posterolateral spinal fusion in an osteoporotic rat mode (estrogen deficiency). Posterolateral intertransverse process spinal fusion using recombinant human osteogenic protein (rhBMP-7) was performed in ovariectomised female rats. OP-1 can be manipulated to enhance fusion rates and fracture healing with or without osteoporosis. Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure, resulting in bone fragility and an increase in susceptibility to fracture. Ovariectomised rats have been used as an osteoporotic model for posterolateral intertransverse process fusion in BMP experimental studies. Many studies have shown rhBMP-7 promotes spinal fusions in posterolateral fusion animal models. Not only is OP-1 able to promote spinal fusion in a standard animal model, but also it has been shown to overcome the inhibitory effects of nicotine in a rabbit posterolateral spinal fusion model. OP-1 Putty (Stryker) is an osteoinductive and osteoconductive bone graft material which consists of the recombinant human Osteogenic Protein (rhBMP-7), and TCP putty containing carboxymethylcellulose sodium (CMC) and tricalcium phosphate. This standard OP-1 device is somewhat different from the one Moazzaz et al used (1). The implication of OP-1 in osteoporotic model will open a new therapeutic window for osteoporotic or osteopaenial patients for the requirements of spinal fusion.
Methods In present study, a total of 42 ovariectomised Sprague-Dawley female rats were randomly assigned to groups receiving 30 µg lactose + 400mg TCP-CMC, 90 µg lactose + 400 mg TCP-CMC, 30 µg rhBMP-7 + 400 mg TCP-CMC and 90 µg rhBMP-7 + 400 mg TCP-CMC. There was a group of rats receiving 400 mg TCP-CMC alone. Spinal fusion was evaluated by manual motion testing at each lumbar segment, Faxitron digital X-ray evaluation using the Lenke grading system, CT scans, DEXA scans and histology.
Results Ovariectomized rats receiving 30 µg lactose + 400mg TCP-CMC, 90 µg lactose + 400 mg TCP-CMC, and 400 mg TCP-CMC alone did not show spinal fusion. OVX rats receiving 90 µg rhBMP-7 + 400 mg TCP-CMC showed significantly higher fusion rates than other groups (P <0.0001). However, the rats receiving 30 µg rhBMP-7 + 400 mg TCP-CMC did not show solid fusion either radiologically and histologically.
Discussion Therefore rhBMP-7, in dose of 90 µg, is able to overcome the inhibitory effects of estrogen deficiency on posterolateral spinal fusion and generate a relatively robust fusion. The effect of the OP-1 on osteoporotic spine is dose-dependent with/without carrier-dependent.