The Aging Skeleton.

Skeletal aging begins after peak bone mass is reached; progressive bone loss then occurs. Peak bone mass may occur at different ages in different skeletal sites and varies between sexes. Accelerated loss of bone occurs in the perimenopausal period in women, whereas more gradual but progressive loss of bone occurs in aging men. Changes in bone quality as well as bone quantity occur during growth and subsequent aging. These include changes in bone microarchitecture which may differ between cortical and trabecular compartments and in different sites, and may impact on bone size and geometry. Changes in material properties of bone matrix may also occur with aging. Loss of bone quantity and altered bone quality with aging may weaken bones and culminate in osteoporosis with an increased risk of fractures. Both genetic and epigenetic mechanisms may predispose to osteoporosis. Cellular and molecular events underlie the alterations in bone quantity and quality. Osteoclastic bone resorption and osteoblastic bone formation, tightly regulated by hormones, growth factors, and cytokines, are organized in coordinated activities resulting in remodeling and modeling. Malignancies, and anti-neoplastic therapies, may impact on the cellular and molecular events in the aging skeleton and produce focal or diffuse skeletal lesions and fractures.