Skeletal effects of fibroblast growth factor mimetic (F2A) in ovariectomized rats.

The current study was designed to determine whether short-term, systemic treatment with F2A, a mimetic for FGF-2, has skeletal effects in ovariectomized (OVX) rats and adverse side effects in non-skeletal tissues. Groups of sham-operated and OVX rats were maintained untreated for 6 weeks postOVX. These groups (N=6) were then treated IP with vehicle or F2A (0.3, 1.0, or 3.0 mg/kg) daily for 14 days. Histomorphometric analyses were performed in the proximal tibial metaphyses. Hematocrit was normal in F2A-treated OVX rats. Although organ function was not evaluated, histological examination of several organs did not detect any abnormalities. F2A treatment did not increase cancellous bone mass regardless of dose, but OVX rats treated with 1 mg/kg did exhibit increased osteoclast surface. All 3 doses of F2A induced a modest increase in cancellous bone formation. Therefore, F2A appears to increase both cancellous bone resorption and formation, but these skeletal processes are in balance so that, unlike FGF-2, cancellous bone mass is not augmented. However, F2A did not induce the anemia and impaired bone mineralization associated with FGF-2. Therefore, local application of F2A for orthopedic procedures would presumably have minimal side effects, even if the peptide is released to the systemic circulation.