Several recent studies have suggested that
flavonols, a class of
phytochemicals with many
biological activities, might exert a protective effect against post-menopausal bone loss. In the present study, we investigated the effects of
quercetin and
kaempferol, two of the major naturally occurring
flavonols on the in vitro
bone resorbing activity of osteoclasts. Our results indicate that both compounds, at concentrations ranging from 0.1 to 100 microM reduce
bone resorption in a time and dose-dependent manner. Significant inhibitory effects were observed at concentrations as low as 0.1 microM especially with
kaempferol. The IC(50)s, or concentration inhibitory of 50% of basal resorption, calculated for
quercetin and
kaempferol were 1.6 and 5.3 microM, respectively. Using highly purified rabbit osteoclasts, we showed that both
flavonols directly induce apoptosis of mature osteoclasts in the same dose-range effective for inhibiting
bone resorption. When osteoclasts were treated with 50 microM of
quercetin and
kaempferol, intracellular
reactive oxygen species levels decreased significantly by 75 and 25%, respectively, indicating these molecules keep their
antioxidant properties at this concentration. However, at concentrations below 50 microM, neither
quercetin nor
kaempferol exerted antiradical action, suggesting that
antioxidant properties cannot fully explain the inhibitory effect on
bone resorption. Finally, we report that
kaempferol-, but not the
quercetin-induced inhibition of
bone resorption was partially abolished by the presence of the pure anti-
estrogen ICI 182780 suggesting that
kaempferol's
estrogenic effect could be involved in the inhibition of
bone resorption. The present study demonstrates that
flavonols widely distributed in human diet such as
quercetin and
kaempferol, exert a potent inhibitory effect on in vitro
bone resorption.