We tested the hypothesis that the age dependence of trabecular bone microstructure differs between men and women and is specific to skeletal site. Furthermore, we aimed to investigate the microstructural pattern of bone loss in aging. Microstructural properties of trabecular bone were measured in vitro in 75 men and 75 age-matched women (age, 52-99 yr) using microCT. Trabecular bone samples were scanned at a 26-microm isotropic resolution at seven anatomical sites (i.e., distal radius, T(10) and L(2) vertebrae, iliac crest, femoral neck and trochanter, and calcaneus). DXA measurements were obtained at the distal radius and proximal femur and QCT was used at T(12). No significant decrease in bone density or structure with age was found in men using microCT, DXA, or QCT at any of the anatomical sites. In women, a significant age-dependent decrease in BV/TV was observed at most sites, which was strongest at the iliac crest and weakest at the distal radius. At most sites, the reduction in BV/TV was associated with an increase in structure model index, decrease in Tb.N, and an increase in Tb.Sp. Only in the calcaneus was it associated with a significant decrease in Tb.Th. In conclusion, a significant, site-specific correlation of trabecular bone microstructure with age was found in women but not in men of advanced age. The microstructural basis by which a loss of BV/TV occurs with age can vary between anatomical sites.