There has been recent evidence about unfavorable effects of estrogen, while selective estrogen receptor modulators (SERM) with estrogen agonist and antagonist actions in a tissue selective manner have been developed. Among them, raloxifen inhibits the risk of vertebral fractures to a similar degree with bisphosphonates. From the same strategy, the study of selective androgen receptor modulators (SARM) has been in progress for the treatment of osteoporosis.