Healing of rat femoral segmental defect with bone morphogenetic protein-2: A dose response study

Objective: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is becoming a common clinical approach to enhance bone repair. There is little or no information in the literature on the dose of rhBMP-2 required for effective healing of critical-sized defects such as those associated with trauma. In this study, we used a segmental defect model to assess the dose response of rhBMP-2 using quantitative and qualitative endpoints. Methods: Femoral defects in rats were replaced with absorbable collagen sponges carrying rhBMP-2 (0, 1, 5, 10 or 20 mu g; N=5). At 4-weeks new bone formation was assessed using quantitative (radiography and microcomputed tomography) and qualitative (histology and backscattered-SEM) endpoints statistically compared. Results: rhBMP-2 showed increased bridging in the gap. Quantitative evaluation presented a bi-phasic dose response curve. Histological assessment revealed that with rhBMP-2 the defect showed the presence of spongy bone with the trabeculae layered with active osteoblasts and osteoclasts. The density and compactness of the bone varied with the dose of rhBMP-2. Conclusions: Our findings revealed that all doses of rhBMP-2 result in new bone formation. However, there is an optimum dose of 12 mu g of rhBMP-2 for bone repair in this model, above which and below which less stimulation of bone occurs.