We used volumetric quantitative computed tomography (QCT) scans to evaluate volumetric bone density (vBMD), geometry, and strength in the thoracic (T8 to T10) and lumbar (L3 to L5) spine and determined how these parameters varied with age, sex, and spinal region. Participants included 690 participants of the Framingham Study, 40 to 87 years old (mean, 61 years). In both women and men, trabecular vBMD declined with age similarly for lumbar and thoracic regions, whereas cortical vBMD and integral vBMD, vertebral strength, and compressive force declined more at the lumbar spine than thoracic spine (interaction, p < 0.01). Notably, in men, cortical vBMD increased (β = 0.0004, p = 0.01), and vertebral strength did not change (β = 1.9305, p = 0.66) at the thoracic spine with age. In both women and men, vertebral cross-sectional area increased less and the factor-of-risk increased more with age at the lumbar than at the thoracic region (interaction, p < 0.01). For example, in women, the factor-of-risk for forward flexion increased (worsened) with age 6.8-fold more in the lumbar spine (β = 0.0157), compared with the thoracic spine (β = 0.0023). vBMD and vertebral strength declined more and the factor-of-risk increased more with age in women than men (interaction, p < 0.01). For instance, integral vBMD for the lumbar spine declined 36% from 40 to 75 years of age in women compared with 18% in men. There was little or no age-related change in the forces applied to the thoracic vertebrae in either women or men. Age-related changes were greater in the lumbar spine than in the thoracic region and greater in women than men. Whereas women lost bone density and strength at both the thoracic and lumbar spine, in men, vertebral strength declined only at the lumbar spine. Our study confirms the importance of evaluating determinants of vertebral strength in both the thoracic and lumbar spine and in both women and men to understand mechanisms underlying the structural failure of vertebral bodies with aging.