Genetics of osteoporosis

Certain aspects of osteoporosis have strong genetic influences. This finding is derived from genetic epidemiological analyses which show that, in women, a maternal family history of fracture is positively related to fracture risk [1]. Most evidence, however, has come from twin studies on bone mineral density (BMD) [2–4]. For BMD, heritability has been estimated to be high: 50–80% [2–4]. Thus, although twin studies can overestimate heritability, a considerable part of the variance in BMD values might be explained by genetic factors, while the remaining part may be due to environmental factors. This also suggests that there are ‘bone density’ genes, variants of which will result in BMD levels that are different between individuals. These interindividual differences in BMD levels can become apparent in different ways – as differences in either peak BMD or rate of bone loss at an advanced age.

The heritability estimates of osteoporosis suggest considerable influences from environmental factors which can modify the effect of genetic predisposition. The gene–environment interactions could include diet, exercise and exposure to sunlight, for example. While genetic predisposition will be constant during life, environmental factors tend to change during the different periods of life resulting in different ‘expression levels’ of the genetic susceptibility. Ageing is associated with a general functional decline in overall activity resulting in less exercise, less time spent outdoors, changes in diet, etc.