title: Unresolved issues in osteoporosis in men.
abstract: Fragility fractures in men are a public health problem. The increasing longevity in men is likely to increase the public health burden of fractures in men. This problem remains unrecognized by doctors, the public and governments. About one third of all hip fractures occur in men but the incidence and gender ratio varies from country to country for reasons that are not understood. The prevalence of spine fractures is about half that of women in most studies, but similar to that of women in several other studies. The incidence of spine fractures is uncertain but is likely to be about half that of women except in 80+ year olds, when it appears to be similar. The causes of the higher mortality in men than in women following hip or spine fracture are not well defined. Areal bone mineral density (aBMD) predicts fracture risk in men; the relative risk for spine and hip fracture conferred by a 1 SD lower aBMD, or by a prevalent fracture, is similar in men and women. The age-specific absolute risk (number of cases per 1,000 per year) conferred by a given hip aBMD is similar in men and women. The age-specific absolute risk conferred by aBMD at the calcaneus or radius for spine fracture is similar for men and women. If the absolute and relative risks are similar then the lower incidence of fractures in men than women may reflect the lower proportion of the male population distribution below a given structural determinant of bone fragility. That is, at any age, there may be fewer men than women with smaller bones, lower volumetric bone mineral density (vBMD), thinner trabeculae or cortices, architectural disruption, or higher remodeling rates. Higher mortality and fewer falls may also contribute to the lower incidence of fractures in men. This tail end of the male population distribution (for traits like bone size, vBMD, architecture, and remodeling rates) is the likely source of fracture cases in males. Hypogonadism is a risk factor for osteoporosis. However, the definition, prevalence, causes and structural consequence of hypogonadism are inadequately defined. At what level of testosterone is bone balance negative? What structural determinants of axial and appendicular strength are regulated by testosterone, estrogen, growth hormone (GH), insulin like growth factor 1 (IGF-1) (or their interactions)? Is reduced bone size in men with spine or hip fractures due to failed growth-related or age-related periosteal expansion? If reduced vBMD is due to reduced accrual, is this due to reduced cortical thickness? What factors regulate and coregulate the periosteal and endocortical modeling and remodeling? Are reduced trabecular numbers due to failed formation at the growth plate, excess resorption of primary trabeculae or reduced formation of secondary trabeculae? Is reduced trabecular thickness due to failed prepubertal or pubertal bone formation? Is reduced cortical and trabecular thickness during aging due to excessive endosteal resorption or reduced bone formation? If the former, is this due to increased remodeling sites or increased resorption depth? Most evidence favors reduced bone formation as the cause of bone loss with trabecular bone loss occurring by reduced formation and thinning more than by increased resorption and loss of connectivity. Cortical bone loss is less than in women because endocortical resorption is less and periosteal apposition is greater. If the reduced bone formation is most important, is this due to reduced osteoprogenitors, reduced osteoblast matrix synthesis or early osteoblast apoptosis? Anti-spine-fracture efficacy has been demonstrated in only one randomized heated with alendronate drug in men. The gaps in our knowledge remain large.
authors.affiliation: Austin & Repatriation Medical Center, University of Melbourne, Melbourne, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Seeman
mesh_terms: D001842:Bone and Bones / Q000473:pathology; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000150:complications / Q000453:epidemiology* / Q000473:pathology