Interaction of genetic and environmental influences on peak bone density.

Risk of osteoporotic fracture in later life relates to both age and menopause-related bone loss but also to peak bone density achieved in early adulthood. Several studies have shown that genetic influences make a major contribution to variance in adult bone density, but environmental factors such as dietary calcium and physical activity also contribute a large proportion of observed variance in bone density. Previous hypotheses have suggested that the effect of certain environmental factors, such as hormonal and dietary influences, may be permissive to development of peak bone mass. Consideration of the evidence for the interaction between environmental influences, such as physical activity and nutrition, and genotype leads us to propose that environmental factors interact to allow or prevent full expression of bone density genotype. This expansion of the 'threshold' hypothesis can include the effects of sex, physical activity and dietary calcium in a model that allows more systematic study of the determinants of peak bone density and thereby more rational intervention to augment bone density in early adulthood.