Purpose of review: Osteoporosis is a common disease with a strong genetic component characterised by reduced bone mass and an increased risk of fragility fractures. Several advances have been made over recent years in understanding the genetic basis of susceptibility to osteoporosis. This paper will review recent developments in this area.
Recent findings: Twin studies have shown that genetic factors contribute to osteoporosis by influencing bone mineral density and other determinants of fracture risk such as ultrasound properties of bone, skeletal geometry, and bone turnover. In the normal population, many different genes contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Whereas the effect size of individual genes is small, meta-analysis has been successfully used in many cases to define the role of individual polymorphisms in predisposing to osteoporosis. Linkage studies in humans and experimental animals have identified several quantitative trait loci that regulate osteoporosis-related phenotypes, and many genes that cause monogenic bone diseases have been identified by use of this approach. It has been found that subtle polymorphisms in some of these genes also contribute to regulation of bone mass in the normal population.
Summary: Research has recently begun to clarify the genes and genetic variants that predispose to osteoporosis and regulation of bone mass. Clinical applications of this research include the identification of genetic markers for assessment of fracture risk and the identification of novel molecular targets for the design of drugs that can be used to treat bone disease.