Differential effects of genistein, estradiol and raloxifene on rat osteoclasts in vitro.

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. It is not clear whether mechanism of action of genistein on bone turnover is distinct from that of estradiol or raloxifene. The aim of the present study was to investigate the effects of genistein on the formation of osteoclasts from neonatal rat bone marrow cells in vitro, and compare them with those of estradiol and raloxifene. Formation of osteoclasts was stimulated by 1,25-dihydroxyvitamin D3, added to the culture media on the second day after plating, together with genistein (10(-8)-10(-5) M), estradiol (10(-10)-10(-7) M) or raloxifene (10(-9)-10(-6) M). The bone marrow cell culture lasted 7 or 9 days. Number of osteoclasts and number of osteoclast "ghosts" (necrotic giant cells) were determined. Genistein, estradiol and raloxifene, at some concentrations, decreased the number of osteoclasts after 9-day culture of bone marrow cells. Genistein decreased the number at 10(-8) M because of decreasing the viability of osteoclasts, whereas at 10(-5) M due to attenuation of osteoclast formation. Estradiol decreased the osteoclast number at 10(-9) M due to decreasing their viability, whereas at 10(-8) and 10(-7) M it was the effect of both decreasing the viability and inhibition of the formation. Decreases in the number of osteoclasts caused by raloxifene (10(-9), 10(-8) M were the effect of decreasing the viability of these cells.