STIMULATION OF BONE-FORMATION BY INTRAOSSEOUS APPLICATION OF RECOMBINANT BASIC FIBROBLAST GROWTH-FACTOR IN NORMAL AND OVARIECTOMIZED RABBITS

The effect on intraosseous bone formation of a single local injection of recombinant human basic fibroblast growth factor into the distal fe mur was examined in normal and ovariectomized rabbits. In normal rabbi ts, basic fibroblast growth factor increased bone mineral density arou nd the injected site in a dose-dependent manner at 4 weeks, with signi ficant effects at concentrations of 400 mu g and greater. Doses of 400 and 1,600 mu g of basic fibroblast growth factor increased bone miner al density by 8 and 9%, respectively, compared with the opposite contr ol femur. Histological examination showed that basic fibroblast growth factor (400 mu g) induced the proliferation or recruitment of undiffe rentiated mesenchymal cells around the existing trabeculae at 3 days a fter the injection. For the first 2 weeks, osteoid formation was stron gly stimulated, and this was followed by mineral apposition for anothe r 2 weeks, at which time the femurs were harvested. Consequently, basi c fibroblast growth factor stimulated intraosseous bone formation at 4 weeks. We speculate that the direct action of basic fibroblast growth factor an bone formation may be to stimulate proliferation or recruit ment of minimally differentiated mesenchymal cells and to initiate the cascade of events in later stages of bone formation. In ovariectomize d rabbits, basic fibroblast growth factor (400 mu g) also increased bo ne mineral density, histomorphometrical bone formation markers, and tr abecular connectivity to levels similar to those in rabbits who had re ceived sham operations.