The aim of this study was to investigate the possible inhibitory effec
t 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 measu
ring the urinary excretion of [H-3]. The animals were fed a purified d
iet devoid of naturally occurring flavonoids. In the intact rats, the
daily meal was given either as a single portion or divided into four p
ortions, a procedure known to lead by itself to a decrease in bone res
orption. 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 d
ecrease 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 prevent
ed the increase in bone resorption induced by castration, the effect b
eing dose-dependent between 50 and 400 mg/kg B.W. In contrast to 17 be
ta-estradiol, a 5-week treatment with ipriflavone failed to prevent th
e OVX-induced uterine atrophy. Significant inhibition of bone resorpti
on was also seen in intact animals, provided they rapidly ingested the
daily meal. Actually, the decrease in bone resorption induced by port
ioning the daily food masked the inhibitory effect of ipriflavone in i
ntact animals. In conclusion, ipriflavone can decrease bone resorption
in both intact and OVX animals given a purified diet as a single dail
y meal. In the OVX model, ipriflavone mimics the osteoprotective effec
t of estrogen. However, the lack of a uterotropic effect suggests that
the compound can discriminate between bone and reproductive tissues.