Abstract: AIMTo determine whether low dose of estrogen in combination with ginsenosides can completely prevent bone loss in ovariectomized rats. METHODSFour-month-old ovariectomized rats were treated either with 100 and 300 mg·kg^-1 of ginsenosides or 30 and 100 μg·kg^-1 of 17α-ethynylestradiol alone, or ginsenosides 100 mg·kg^-1 in combination with 17α-ethynylestradiol 30 μg·kg^-1 for 10 weeks. Double in vivo fluorochrome labeling was made. The undecalcified longitudinal proximal tibial metaphyseal sections were processed and stained with Goldner's trichrome for histomorphometric analysis of the bone. RESULTSBody weights and serum cholesterol were increased in ovariectomized (OVX) rats. The rats lost 74% of bone volume and high bone turnover was induced after OVX compared with the sham group. Bone volume increased by 205% in the high dose estrogen treated group while it was increased by 105% in the low dose group. The two doses of estrogen were shown to inhibit osteoclasts surface (by -65% and -55%, P<0.01) and decrease bone turnover rate (by -85% and -83%, P<0.01). High dose of estrogen was found to inhibit growth and stimulate uterin weight gain in rats while low dose did not. High dose of ginsenosides increased bone volume by 84% (P<0.01) and decreased bone turnover rate by -64% (P<0.05) while lower dose of ginsenosides did not. However, low dose ginsenosides combinated with low dose estrogen achieved well preventive effects: increase of 202% in bone volume, decrease of 66% in bone turnover rate and 72% in osteoclasts surface. The combined effect in preventing bone loss equals to that the high dose of estrogen alone did. CONCLUSIONUse of low dose of estrogen plus ginsenosides showed synergistic effect on prevention of osteoporosis induced by ovariectomy.