Recent technical advance for making of gene modified mice includes gene targeting and transgenic mice are clarify the biological function of its targeted molecules. The evidence from gene modified mice on sex-steroid hormones may contribute to develop clinical drugs for osteoporosis treatment especially. Gene deficient mice of the sole enzyme for estrogen synthesis (aromatase), estrogen receptor and androgen receptor deficient mice have great potential to elucidate further mechanisms of pathogenesis of osteoporosis.