The Genetics of Osteoporosis

Abstract

Osteoporosis is a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and an increased risk of fracture. Bone mass in later life depends on a balance between the amount of bone gained during growth and the subsequent rate of loss. Bone mass is a complex trait that is subject to several environmental influences. Genetic factors are now recognized to be extremely important in determining bone mass, but the genes that are involved remain incompletely defined. The candidate gene approach has been most widely used in studying the genetic basis of osteoporosis. Clinical studies have shown positive correlations between polymorphisms of several candidate genes and bone mass, including the vitamin D receptor, collagen 1α1, estrogen, transforming growth factor beta and interleukin-6. No single gene has been found to dominate bone density however, consistent with the view that bone mass is under polygenic control. It is probable that future studies will identify other genes that regulate bone mass and it could be that by using combinations of polymorphisms in several candidate genes it will be possible to identify subgroups of individuals at high or low risk of osteoporosis. A potential application of this technology in the future would be in screening for osteoporotic fracture risk, possibly in combination with standard means of risk assessment such as bone densitometry and biochemical markers.