Although it has been accepted that osteoporosis is common in women, only recently have we become aware that it is also widespread in men; one in twelve men in the UK have osteoporosis. In many cases, there are recognisable causes for their osteoporosis, but a significant proportion (approximately one third) of these men have idiopathic disease. A major problem is that these cases are difficult to treat. An important therapeutic strategy would be to identify men at risk from osteoporosis sufficiently early, so that they can begin preventative measures. Moreover, development of novel means of treating these men would be an important clinical advance. With the emphasis on osteoporosis in women, however, the cellular and molecular basis for male idiopathic osteoporosis (MIO) is still poorly understood. Nevertheless, there are some aspects of skeletal regulation which may be specific for men and which could form the basis for addressing these problems. Thus, the importance of oestrogen in maintaining the adult skeleton in men as well as women implies that bone cells in men can respond to low levels of the hormone. Both oestrogen receptor (ER) alpha and beta are expressed in bone in vivo, which may be important for oestrogen action on bone in men. Furthermore, in osteoporosis generally, there is increasing evidence for defective osteoblast differentiation such that there is a surfeit of adipocytes over osteoblasts. A low peak bone mass is a powerful risk factor for osteoporosis in later life; bone formation and, by implication, osteoblast differentiation, is key to the mechanism by which it is accrued. GH and IGFs are important for regulating osteoblast differentiation. Evidence now suggests that they are associated with bone mineral density, particularly in men. The genes for ERs, GH and IGF-I might be useful candidates with which we can begin to detect men at risk from osteoporosis. Furthermore, the mechanisms by which oestrogen, GH and IGF-I regulate the male skeleton could provide the basis for developing novel means of treating MIO.

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