Heberden oration: IP80. Prevention of Osteoporotic Fracture: Before the Cradle and Beyond the Grave

Abstract

Osteoporosis is a skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The cumulative incidence of fracture from age 50 years is estimated at around 50% among white women and 20% among white men. Preventive strategies against osteoporotic fracture can be targeted throughout the life course. Thus, modification of physical activity and dietary calcium/vitamin D nutrition in the elderly and during midlife, should complement high risk approaches entailing appropriate measurement of bone mineral density and targeting of anti-resorptive and formation stimulating drugs. Prevention of osteoporotic fracture can also be directed earlier in the life course. Environmental influences during early life interact with the genome in establishing the functional level of a variety of metabolic processes which are involved in the pathogenesis of osteoporotic fracture. The evidence that osteoporosis risk might be programmed in this way stems from four groups of studies: (1) Epidemiological studies which confirm that subjects who are born light and whose growth falters in the first year of postnatal life, have significantly lower bone size and mineral content, at age 60 to 75 years; (2) Epidemiological cohort studies have demonstrated that subsequent lower trajectories of childhood growth are associated with an increased risk of hip fracture among such men and women; (3) Detailed physiological studies of candidate endocrine systems which might be programmed have shown that birthweight and growth in infancy alter the functional settings of the GH/IGF-1, and hypothalamic pituitary adrenal axes; (4) Studies characterising the nutrition, body build and lifestyle of pregnant women which relate these to the bone mass of their newborn offspring, have identified a number of important determinants of reduced fetal mineral accrual (maternal smoking, low maternal fat stores and maternal vitamin D deficiency, intense levels of weight-bearing physical activity in late pregnancy). Follow-up studies of randomised controlled trials of vitamin D supplementation in infancy suggest persisting benefits in adolescence and young adulthood. These data suggest that undernutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism, which might independently influence the later risk of osteoporotic fracture.