Effects of single and cyclical local injections of basic fibroblast growth factor on cancellous bone defects in rabbits

Local administration of basic fibroblast growth factor (bFGF) has anabolic effects on bone formation. A delivery system for local treatment is required to increase efficacy because of its short half-life. However, little is known about the effects of cyclical local injection of bFGF. We evaluated the effects of single and cyclical local injection of bFGF at a cancellous bone defect in the femoral condyle in rabbits. Using the "vehicle only" as a control, a single low dose (40 A mu g), single high dose (120 A mu g), or cyclical low dose (40 A mu g, three times) of bFGF was injected percutaneously into a bone defect implanted with a gelatin sponge. The rabbits were killed at 4 weeks after surgery and the femurs were harvested for evaluation. Both single and cyclical administration of bFGF dose-dependently increased the amount of new bone formation in the bone defect using radiographs (P < 0.01) and bone mineral density (BMD) measurements (P < 0.01) compared to controls. However, only high-dose bFGF injection significantly increased the cancellous bone volume at the bone defect (P < 0.05) compared to controls, using bone histomorphometry. Cyclical injection of bFGF significantly increased the number of runt-related transcription factor-2 (Runx2)-positive cells compared to single low- and high-dose bFGF administration (P < 0.01 and P < 0.05, respectively), and single high-dose and cyclical administration significantly increased the number of osteopontin-positive cells compared to controls (P < 0.01), based on immunohistochemical analysis. These results suggest that high-dose injection of bFGF, at the very early stage of cancellous bone healing, is more effective in increasing cancellous bone volume, and cyclical injection of bFGF may stimulate osteoprogenitor cells.