Pathogenesis of osteoporosis

Abstract

Fractures, the clinical outcome associated with osteoporosis, have a complex pathogenesis involving, in most cases, both trauma to the bone and increased skeletal fragility. Recent evidence also suggests that the geometry of the bone is important in determining fracture risk, and geometric properties are in part genetically determined. Skeletal fragility is largely determined by bone mass and the microstructure of bone. Loss of trabeculae and their connections has been well documented and undoubtedly contributes to risk of some fractures. Microdamage has also been shown to occur within the skeleton and could contribute to fragility. Peak bone mass is a major factor in determination of subsequent fracture risk and it has both genetic and environmental determinants. Twin studies have suggested a major genetic contribution and that a few genes may be responsible, but these genes have not been clearly identified. Nutrition, especially calcium intake, and exercise also contribute to the determination of peak bone mass and are especially important during the major period of bone acquisition up to the age of 18. Bone loss among women begins in the perimenopausal period, although loss from the hip begins earlier. The loss is associated with both estrogen and androgen concentrations. Later in life other factors such as the development of secondary hyperparathyroidism may contribute to the continued loss of bone. Males lose bone at about half the rate of females, but the underlying contributing factors are not well documented. The pathogenesis of osteoporotic fractures is complex, but this allows for the development of multiple interventions, which may reduce the frequency of such fractures.