Appropriate and Effective Dosage of BMP-2 for the Ideal Regeneration of Calvarial Bone Defects in Beagles

BACKGROUND: Although bone morphogenetic protein-2 (BMP-2) is a potent growth factor, the appropriate and effective dosages for ideal bone formation according to defect size and type remain to be established. This study was designed to measure the effects of BMP-2 on calvarial defects in the beagle dog, by means of three-dimensional computed tomographic imaging. METHODS: Eight beagles of equal age and weight were divided into one control and three experimental groups. After creating four circular 20-mm diameter defects, a BMP-2/tricalcium phosphate scaffolding mixture with concentrations of BMP-2 was introduced. The defect filling response was assessed until 16 weeks by three-dimensional computed tomograpy for the thickness, area, and density of the regenerating bone. RESULTS: Statistically significant responses to BMP-2 were observed. The mean thicknesses of the regenerated bone were 1.6 mm for the control group and 1.6, 2.1, and 2.8 mm for 10, 50, and 200 µg/ml, respectively. As the original mean thickness of the calvarial bone in the beagles was 2.0 mm, a 50-µg quantity of BMP-2 proved to be ideal for 2-cm calvarial defects. The original surface area of the defect created was 314 mm. The mean surface areas of the regenerated bone were 181.94 mm for the control group, and 237, 276, and 288 mm for 10, 50, and 200 µg/ml. CONCLUSIONS: BMP-2 promotes anatomically significant bone regeneration in critical-size cranial defects in this model, with an optimal dose-response at 50 µg/ml and without hyperosteogenesis or hypo-osteogenesis.