This study compared the ability of genistein, a soy isoflavone, with that of 17 beta-estradiol to prevent bone loss in cadmium (Cd)-exposed ovariectomized (OVX) rats during growth. Female Wistar rats (4 weeks old) were either sham-operated (SH; n = 9/group) or OVX and placed on experimental diets (n = 9/group): OVX; OVX rats fed 50 ppm of CdCl(2) (OVX-Cd); OVX fed 50 ppm of CdCl(2) and 10 microg/kg of body weight genistein (OVX-Cd-G); and OVX fed 50 ppm of CdCl(2) and 10 microg/kg of body weight estrogen (OVX-Cd-E). All rats were given free access to AIN-76 modified diet and drinking water, with or without Cd, for 8 weeks. The OVX groups gained more body weight than the SH group. Femoral weight was increased by feeding genistein and estradiol, whereas femoral length among groups was not significantly different. Femoral Cd content was significantly higher in the OVX-Cd group than in the other groups. Both serum osteocalcin and calcium (Ca) concentrations, as well as urinary Ca, were significantly higher in the OVX-Cd group than in the other groups. Urinary excretion of Cd was significantly increased in Cd-OVX-G rats, and fecal Cd excretion was increased by feeding both genistein and estradiol. Femoral histomorpological changes in proliferative cartilage and hypertrophic cells in the OVX-Cd group showed that both cell types were decreased by feeding Cd, and irregular arrangements were observed in proliferative cells. However, both cells types exhibited normal distribution in OVX-Cd-G and OVX-Cd-E groups. These findings suggest that Cd/OVXinduced osteopenia or osteoporosis probably results from an increase in bone turnover. Genistein may be involved in stimulating Cd excretion and inhibiting Ca excretion from bone.