Sex hormones are major regulators of bone turnover and remodeling in both genders. Estrogens reduce bone loss by inhibiting the generation of new osteoclasts, reducing the activation frequency of the BMU and promoting apoptosis of mature osteoclasts via mechanisms that are not well understood. Some of the effects of estrogen seem to be mediated via the modulation of growth factors and cytokines, while others are associated with binding to at least two different estrogen receptors (ERa, ERb). A reduction in circulating endogenous estrogen levels, as occurs during and after menopause, has been shown to prolong osteoclast survival and stimulate the recruitment and hence generation of osteoclasts. The result is an increase in the activation frequency of the BMU, reflected in a high bone turnover state.14 While there is no doubt that androgens (i.e., testosterone, dihydrotestosterone) play a dominant role in male bone health, it also appears that circulating estradiol levels are important for bone development in younger men, and for bone turnover in elderly men. However, it remains contentious just how important blood estradiol relative to blood testosterone levels are for the maintenance of bone in (older) men. Recent findings suggest that aromatization of testosterone to estradiol plays a significant role in the regulation of bone metabolism, and, ultimately, influences age-related bone loss in elderly males.15
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