The discoveries that sex steroid receptors for estrogen [estrogen receptor (ER)], androgen [androgen receptor (AR)], and progesterone [progesterone receptor (PR)] are present in the bone-forming osteoblasts (OB) and bone-resorbing osteoclasts (OCL), and that these cells are targets for sex steroid action, have generated much excitement in the field of bone biology. The subsequent discoveries that the sex steroids regulate the production of growth factors and cytokines in these OB and OCL cells and that these factors mediate much of the steroid action on the skeleton have added to the excitement and complexity of the system. Because of the required brevity of this minireview, we will discuss only selected aspects of this field using a limited number of references and review articles. For more information in this field, readers are referred to several recent books and chapters that review bone biology, bone diseases, and the role of sex steroids in bone biology and disease (1–8). As a brief background to this unique system, the skeletal maintenance involves a continuous remodeling at discrete sites termed bone-remodeling units (BRU). As outlined in Fig. 1, the multinucleated boneresorbing OCLs first dissolve bone at these BRU sites, resulting in resorption cavities. While the mechanism (s)/signal (s) that initiates resorption at a given site is unknown, there appears to be a marked regulation of overall bone resorption via the regulation of the OCL differentiation and activity (5–8). These processes are discussed in more detail below. The bone-forming OBs are then recruited by unknown signals, to replace the previously resorbed bone. The identities of the primary factors that couple these processes of resorption to formation to maintain bone mass are also addressed later in this review and are still the subject of much debate. During periods of skeletal growth in children, the increase in bone formation largely involves bone modeling (accretion of bone at surfaces in the absence of bone resorption). The response to mechanical stresses also utilizes mostly modeling. During early adulthood (20–40 yr), bone resorption and formation are in balance and bone mass is maintained. The increased serum estrogen (E) level, which occurs at the onset of puberty in girls, is accompanied by an increase in growth velocity and, ultimately, in the closure of the epiphyseal growth plate and the cessation of linear growth (9). E is the primary hormone responsible for maintaining bone mass in adult women and may serve a similar role along with androgen, in adult men. Finally, during periods of bone loss, such as in postmenopause in women and aging in both genders, bone resorption outpaces bone formation and, in some cases, the bone loss is sufficient to cause osteoporosis.

It is currently accepted that in postmenopausal females, a deficiency of E results in osteoporosis, whereas in aging males, the deficiency of E and androgens (A) may lead to bone loss (1–3). Ovariectomized (OVX) animals and postmenopausal women experience increased bone turnover, increased bone resorption, and an overall decrease in bone mass. On the other hand, E replacement therapy inhibits this bone loss by inhibiting bone turnover and bone resorption, which prevents the development of osteoporosis (1, 3). Although, the complete mechanisms of action of E in this protection against bone loss are still unclear, new studies are beginning to elucidate the molecular processes involved. The following review summarizes some of the important molecular events in the actions of sex steroids, primarily estrogens, which