Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem

Although it has been accepted that osteoporosis is common in women, only re cently have we become aware that it is also widespread in men; one in twelv e men in the UK have osteoporosis. In many cases, there are recognisable ca uses for their osteoporosis, but a significant proportion (approximately on e third) of these men have idiopathic disease. A major problem is that thes e 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 tr eating these men would be an important clinical advance. With the emphasis on osteoporosis in women, however, the cellular and molecular basis for mal e idiopathic osteoporosis (MIO) is still poorly understood. Nevertheless, t here are some aspects of skeletal regulation which may be specific for men and which could form the basis for addressing these problems. Thus, the imp ortance of oestrogen in maintaining the adult skeleton in men as well as wo men 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 vive , which may be important for oestrogen action on bone in men. Furthermore, in osteoporosis generally, there is increasing evidence for defective osteo blast differentiation such that there is a surfeit of adipocytes over osteo blasts. 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 fo r ERs, GH and IGF-I might be useful candidates with which we can begin to d etect men at risk from osteoporosis. Furthermore, the mechanisms by which o estrogen, GH and IGF-I regulate the male skeleton could provide the basis f or developing novel means of treating MIO.