The developmental origins of osteoporotic fracture.

Undernutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the GH/IGF-1 and HPA axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have suggested that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Finally, childhood growth rates have been directly linked to the risk of hip fracture many decades later. Further work is needed to use this approach to develop novel therapeutic and preventative strategies to reduce the burden of osteoporotic fractures in the population.