Osteoclastic resorption increases at menopause and remains high during aging. The complex mechanism responsible for this increase involves cytokines and growth factors secreted by stromal cells and/or by osteoblasts and cells in the hematopoietic microenvironment. Although estrogen receptors have been found mainly on osteoblasts and their precursors, the stromal cells, they have also been demonstrated on osteoclast precursors. Raloxifene is a selective estrogen receptor modifier (SERM) that has the beneficial effects of estrogens on bone tissue but no estrogen agonist effects on the breast and uterus. Although recent data have established that the mechanism of action of estrogens and SERMs is far more complex than was previously thought, the reason for the tissue selectivity of these molecules remains unknown.