Bone modeling: the first step in the bone-building process

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. Bone mass in later life depends upon the peak attained during childhood and adolescence, and on the subsequent rate of bone loss. Factors that influence the accumulation of bone mineral during childhood and adolescence include heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birth weight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems, such as the hypothalamic-pituitary- adrenal axis, and the growth hormone/insulin-like growth factor I axis. Maternal smoking, diet, and physical activity levels appear to modulate bone mineral acquisition during intrauterine life. Furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. Optimization of maternal nutrition and intrauterine growth should also be included in preventive strategies against osteoporotic fracture, albeit for future generations