INHIBITION OF PARATHYROID HORMONE-STIMULATED RESORPTION IN CULTURED FETAL-RAT LONG BONES BY THE MAIN METABOLITES OF IPRIFLAVONE

Ipriflavone is an isoflavone derivative used in the prevention and tre atment of postmenopausal and senile osteoporosis in humans. To assess the potential contribution of the main in vivo ipriflavone metabolites (M1, M2, M3, and M5) on the pharmacological properties of the drug, w e investigated their effect on osteoclastic resorption induced by the well-known stimulator of bone resorption bovine parathyroid hormone fr agment 1-34 (bPTH 1-34). The study was carried out using fetal rat lon g bones in stationary cultures. The amount of osteoclastic resorption was determined by assaying for 5 days the release from bones in the me dia of previously incorporated Ca-45. All metabolites were effective a t inhibiting osteoclastic resorption. Maximal potency was shown by M3, characterized by a significant effect at 10 mu M (P < 0.01) and by an IC50 value of 17 mu M. M2 was about threefold less potent than M3 (IC 50 = 46 mu M). M1 and M5 were the least active compounds with an IC50 value of 117 and 200 mu M, respectively. The present evidence indicate s that metabolites of ipriflavone, in particular M3 and M2, inhibit bP TH 1-34-induced bone resorption in fetal rat long bones. Accordingly, they may play an important role in the pharmacological effects of the drug.