The material composition and structural design of bone determine its strength. Structure determines loads that can be tolerated but loads also determine structure. Bone modifies its material composition and structure to accommodate loads by adaptive modeling and remodeling. Adaptation is successful during growth but not aging because accumulating insults, including a reduction in the volume of bone formed in the basic multicellular unit (BMU), increased resorption in the BMU, increased remodeling rate in midlife in women and in some men because of sex hormone deficiency, and in both sexes in old age as a consequence of secondary hyperparathyroidism and reduced periosteal bone formation, all of which compromises the material composition of bone and its structure. An understanding of the mechanisms of adaptation and failed adaptation provides rational approaches to interventions that can prevent or restore bone fragility.