The Genetics of Osteoporosis

Abstract

Genetic factors play an important role in the pathogenesis of osteoporosis. Studies in twins and in normal families indicate bone mineral density and the susceptibility to fracture is under strong genetic control. The genes responsible are incompletely defined but current evidence suggests that several genes, each with small effects, are responsible, rather than a few genes with large effects. Most research on the genetics of osteoporosis has used the candidate gene approach whereby polymorphisms of candidate genes are related to bone mass in population studies and case-control studies. Polymorphisms of the vitamin D receptor gene (VDR) have been related to bone mass in some populations with effects that seem to be modified by calcium and vitamin D intake, although in other studies no association has been found. Polymorphisms of the oestrogen receptor gene have also been associated with bone mass and it has been suggested that these may interact with VDR polymorphisms to identify a subgroup of individuals at high risk of osteoporosis. Another polymorphism, which affects a regulatory site in the collagen type 1 alpha I (COLIA1) gene, has also been defined which seems to predict the presence of osteoporotic fractures, independent of bone mass, raising the possibility that this polymorphism could help identify individuals at risk of fracture. Much work remains to be done to clarify the molecular basis for genetic regulation of bone mass and to identify other genes which contribute. As these studies progress, it is likely that our understanding of the pathophysiology of osteoporosis shall improve and that genetic screening tests for osteoporotic risk will be developed to help target individuals at high risk of osteoporosis for preventative therapy.