title: Pathogenesis of bone fragility in women and men.
abstract: There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.
authors.affiliation: Department of Endocrinology, Austin and Repatriation Medical Centre, Heidelberg 3084, Victoria, Australia. egos@unimelb.edu.au
authors.forename: Ego
authors.initials: E
authors.lastname: Seeman
mesh_terms: D000293:Adolescent; D000368:Aged; D000375:Aging / Q000378:metabolism*; D015519:Bone Density; D001846:Bone Development / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000209:etiology* / Q000378:metabolism; D012737:Sex Factors