Ipriflavone (IP), a synthetic isoflavone has been reported to prevent bone loss in both postmenopausal women and ovariectomized (ovx) rats. The purpose of this study was to compare and contrast some of the bone protective mechanisms of TP to those of 17 beta-estradiol (E-2) in ovarian hormone deficiency. Forty-eight 95-day-old Sprague-Dawley rats were assigned to four groups: sham, ovx, ovx+IP, and ovx+E-2. The doses of IP and E-2 were 100 mg and 10 mu g/kg body weight per day, respectively. Rats were fed a diet that contained 0.4% calcium, 0.3% phosphorus, and 0.195 nmol vitamin D-3/g diet. After sacrifice, left femoral bone densities were measured and bone histomorphometry was performed on the proximal tibial metaphysis. Ipriflavone as well as E-2 treatment completely prevented the ovx-induced femoral bone density loss. How ever, in contrast to E-2, IP did not lower the ovx-induced rise in serum alkaline phosphatase (ALP) activity or insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 concentrations. On histomorphometry analysis, the ovariectomy-induced increase (P < 0.09) in bone formation rate (BFR) was significantly (P < 0.05) suppressed by E-2 treatment, whereas this higher BFR was maintained in IF-treated animals. These findings indicate that IP is effective in preventing the ovx-associated bone loss. The bone protective mechanisms of IF in ovarian hormone deficiency may be different from those of E-2 and may involve increased rates of bone formation.