The incidence of osteoporotic fractures increases with advancing age. Despite advances in therapy, reversal of bone loss in established osteoporosis remains problematic and deformities and disability due to fractures often persist. Therefore the logical approach to osteoporosis treatment is preventive. Risk of fracture is determined largely by bone density, which is the end result of peak value achieved at skeletal maturity and subsequent age- and menopause-related bone loss. Thus the determinants of peak bone density and bone loss require full characterization. Environmental and lifestyle factors are important determinants of bone density, particularly physical activity and diet. For example, muscle strength and physical fitness predict bone density, so that regular moderate exercise may help maintain bone mass but probably does not reverse loss. Long-term calcium intake appears to be important for achievement and maintenance of peak bone density, especially in males. Smoking and excessive alcohol intake are deleterious to bone mass. Cultural norms in diet, lifestyle and physical activity obviously have an impact on bone density. Genetic factors have a strong role in determining the wide range in 'normal' peak bone mass. Moreover we have found strong genetic determinants of rates of change of bone mass in the lumbar spine and similar trends for sites in the femoral neck. We have shown previously that genetic factors influence bone turnover indices, particularly osteocalcin. Investigating these relationships with restriction fragment length polymorphisms, we have identified variants of the vitamin D receptor gene which predict osteocalcin levels and presumably bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)