Geriatrics grand rounds: Eve's rib, or a revisionist view of osteoporosis in men

It is widely accepted that estrogen withdrawal following menopause predispo ses women to accelerated bone loss and increased risk of developing osteopo rosis. Although osteoporosis is a significant public health problem for agi ng men as well as women, the cause of osteoporosis in men remains largely u nknown. A substantial number of men with osteoporosis present with bone los s secondary to conditions associated with reduced gonadal steroid hormone l evels. Although hypogonadism is related to bone loss in men, and androgen l evels decline with age in men, it is not at all clear that reduced androgen levels are related to bone loss in older men. What, then, is the role of g onadal steroids in osteoporosis in men? This review focuses on recent resea rch-including clinical investigations of men with genetic disorders of estr ogen action, basic biomedical studies of estrogen receptor "knockout" mice, and population-based comparisons of bone density with gonadal steroids in older men-leading to the surprising conclusion that estrogen plays a vital role in maintenance of bone in men as well as in women. Possible mechanisms whereby reduced estrogen levels might result in bone loss in both sexes ar e also reviewed, as are potential therapeutic implications of a role for es trogen in osteoporosis in men.