Ipriflavone inhibits bone resorption in intact and ovariectomized rats

The aim of this study was to investigate the possible inhibitory effect of ipriflavone on bone resorption in rats. For this purpose, 10-week-old, intact and ovariectomized (OVX) rats, prelabeled from birth with [H-3]-tetracycline, were used. Bone resorption was monitored by measuring the urinary excretion of [H-3]. The animals were fed a purified diet devoid of naturally occurring flavonoids. In the intact rats, the daily meal was given either as a single portion or divided into four portions, a procedure known to lead by itself to a decrease in bone resorption. Ipriflavone, given 7 days after OVX at the dose of 400 mg/kg B.W. daily mixed with the food, led within 2-3 days to a significant decrease in bone resorption equivalent to that of 27.2 mu g/kg S.C. of 17 beta-estradiol. The inhibition was sustained for the length of the experiment, up to 21 days. Ipriflavone given 7 days before OVX prevented the increase in bone resorption induced by castration, the effect being dose-dependent between 50 and 400 mg/kg B.W. In contrast to 17 beta-estradiol, a 5-week treatment with ipriflavone failed to prevent the OVX-induced uterine atrophy. Significant inhibition of bone resorption was also seen in intact animals, provided they rapidly ingested the daily meal. Actually, the decrease in bone resorption induced by portioning the daily food masked the inhibitory effect of ipriflavone in intact animals. In conclusion, ipriflavone can decrease bone resorption in both intact and OVX animals given a purified diet as a single daily meal. In the OVX model, ipriflavone mimics the osteoprotective effect of estrogen. However, the lack of a uterotropic effect suggests that the compound can discriminate between bone and reproductive tissues.