Early healing pattern of statin-induced osteogenesis.

We examined the early histological expressions of vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP)-2 and core binding factor (Cbfa1) in healing bones with and without a statin (simvastatin). Thirty bone defects were created in the parietal bones of 15 New Zealand white rabbits. In the statin group (n=9), the defects were grafted with carriers of collagen matrix mixed with simvastatin solution, and the animals were killed on days 1 (n=1), 2 (n=1), 3 (n=2), 4 (n=2), 5 (n=2) and 6 (n=1) after operation. In the collagen matrix group, the defects were grafted with carriers of collagen matrix mixed with water for injection, and killed on days 1-6 postoperatively. Immunolocalisation studies of the defects grafted with statin showed that VEGF was expressed on day 3 postoperatively, BMP-2 on day 4, Cbfa1 on day 5 and that new bone was formed by day 5. These events occurred one day earlier than in the group grafted with the carrier alone. The statin induced and accelerated formation of bone locally, and triggered the early expression of growth factors that regulate angiogenesis, differentiation of bone cells, and osteogenesis.