Intraosseous BMP implants in rabbits - Inhibitory effect on bone formation

The bone harvest chamber is a model for rapid spontaneous bone healing in r abbits. We have previously shown inhibition of bone formation by using BMP- P on a collagen carrier in this intraosseous model, despite bone formation when depositing BMP-2 on a similar carrier subfascially in the same animals . The doses were 12 and 0.6 mu g/ 5 mm(3) chamber volume. As these findings conflicted with most other experiments dealing with the skeletal response to BMP-2, we repeated the previous experiments with variations. We studied: 1) a lower BMP-P dose, 2) a different type of BMP (BMP-7/OP-1), 3) a diffe rent carrier (hydroxyapatite), 4) a different chamber construction allowing contact with extraskeletal tissue and 5) BMP-2 on the original collagen ca rrier in an acutely inserted chamber in rats. We also studied the border be tween the BMP-P implant and the preexisting bone to see whether BMP-2 cause d premature differentiation of the callus so that proliferation was stopped and a bone cyst formed, The low dose of BMP-2 reduced tissue ingrowth and tended to reduce bone formation. BMP-7 showed the same inhibitory effects a s BMP-2. BMP-2 on a hydroxyapatite carrier also inhibited bone formation in the chamber. In the chamber that allowed contact with extraskeletal tissue , we observed no effects of BMP-2. The border between the BMP-2 implant and the preexisting bone did not look like a cyst wall. BMP-2, from the same b atch, on a similar collagen carrier, regularly increased bone formation in the acutely inserted bone chamber in rats, thereby excluding major defects in the BMP-2 implants. The inhibition in this specific model is a consisten t finding and not due to an overdose, a specific BMP-type, a specific carri er or premature callus differentiation.