The amount of bone mineral mass acquired at the end of growth, the so-called 'peak bone mass', is considered to be a major risk factor for the occurrence of fragility fractures during adult life. Many interrelated factors can influence the accumulation of bone mass during growth, including genetics, sex, ethnicity, nutrition (e.g. calcium, vitamin D, protein), hormonal factors (e.g. sex steroids, insulin-like growth factor I), physical activity and exposure to various risk factors (e.g. alcohol, smoking, certain medications). Family and twin studies have estimated that up to 60-80% of the variance in peak bone mass is attributable to genetic factors. It can be predicted from epidemiological studies that a 10% increase in peak bone mass would reduce the risk of fragility fractures after the menopause by 50%. Intervention studies testing the effects of increasing either calcium intake or physical activity during growth provide evidence that modifying environmental factors can positively influence peak bone mass. Nevertheless, there is large interindividual variability in the response suggesting gene-environment interactions. A few studies have reported associations between some bone-related gene polymorphisms and the osteogenic response to loading or calcium supplementation. Identifying the functionally implicated genes interacting with mechanical loading and/or specific nutrients represents a formidable but hopefully not intractable challenge.