Invited Review: Pathogenesis of osteoporosis

Abstract

Patients with fragility fractures may have abnormalities in bone structural and material properties such as larger or smaller bone size, fewer and thinner trabeculae, thinned and porous cortices, and tissue mineral content that is either too high or too low. Bone models and remodels throughout life; however, with advancing age, less bone is replaced than was resorbed within each remodeling site. Estrogen deficiency at menopause increases remodeling intensity: a greater proportion of bone is remodeled on its endosteal (inner) surface, and within each of the many sites even more bone is lost as more bone is resorbed while less is replaced, accelerating architectural decay. In men, there is no midlife increase in remodeling. Bone loss within each remodeling site proceeds by reduced bone formation, producing trabecular and cortical thinning. Hypogonadism in 20-30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism increase remodeling: more bone is removed from an ever-diminishing bone mass. As bone is removed from the endosteal envelope, concurrent bone formation on the periosteal (outer) bone surface during aging partly offsets bone loss and increases bone's cross-sectional area. Periosteal apposition is less in women than in men; therefore, women have more net bone loss because they gain less on the periosteal surface, not because they resorb more on the endosteal surface. More women than men experience fractures because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition.