Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats

There are no universally accepted agents that will substantially increase b one mass in osteoporotic patients. A number of peptides important in normal bone formation, such as members of the transforming growth factor-beta sup erfamily, are not satisfactory for this purpose either because their benefi cial effects are predominantly local or there is systemic toxicity associat ed with their administration. We have examined the effects of exogenous fib roblast growth factor-1 and -2 (FGF-1 and FGF-2) on bone in vivo, since FGF s have been shown recently to be essential for normal skeletal development, FGF-1 was injected daily (0.2 mg/kg intravenously) for 28 days into the ta il vein of adult female rats immediately following and 6 months after sham operation or ovariectomy (OVX), In rats treated immediately post-OVX, OVX p roduced more than a 30% decrease in tibial bone density, which was prevente d by FGF-1 and estrogen, However, FGF-1 also had an anabolic effect. In sha m-operated rats, FGF-1 increased bone density to 2-fold, whereas estrogen h ad no effect. In rats 6 months post-OVX, severe bone loss and disruption of trabecular microarchitecture occurred similar to that seen in patients wit h severe osteoporosis. In these rats, administration of FGF-1 induced exten sive new woven bone formation with new trabecular-like structures filling m uch of the marrow spaces, and bone density in the tibial metaphysis increas ed 3-fold. FGF-1 and FGF-2 were also administered subcutaneously over the c alvaria of mice in doses of 2-2000 mu g/day for 3 days and shown to produce substantial increases in bone formation when examined morphologically. Thu s, we conclude that both local and systemic FGF-1 increases new bone format ion and bone density, and systemic FGF-1 also appears to restore bone micro architecture and prevent bone loss associated with estrogen-withdrawal.