Genes and Osteoporosis

Abstract

Osteoporotic fracture is the clinical endpoint of a lifetime exposure to factors that cause increased skeletal fragility and affects a large population of elderly women and men. Low bone mineral density predicts the risk of an individual sustaining osteoporotic fracture and can be viewed to represent the cumulative exposure over childhood, adolescence and adult years of a number of genetic and environmental factors that affect bone strength. The study of genetic factors in osteoporosis was previously complicated by the fact that fractures occur relatively late in life and, therefore, establishing pedigrees of affected and unaffected members within a family would be logistically complex. However, bone mineral density measurements that predict osteoporotic fracture have allowed the identification of individuals at increased risk of osteoporosis at a younger age. Bone mineral density values provide a quantitative measure of skeletal strength with normally distributed values. Individuals at increased risk of sustaining osteoporotic fracture lie within the lower end of this normal range. This has the advantage of replacing the categorical classification of fracture versus non-fracture with a continuously distributed variable and allows the identification of the degree to which genetic and environmental factors contribute to the variance of this trait. Moreover the identification of genetic factors that determine bone strength must consider the trait in the light of environmental exposure. It is conceivable that genes that predispose to low bone density and fracture in one environment may be protective in a different environment. The study of genetic factors that determine bone strength, therefore, must consider the environment in which the genes are exposed and the context in which those observations are made.