Osteoporosis is a skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility [1
]. It is the commonest bone disorder in Western populations, and an important public health issue because of the potentially devastating consequences of fragility fracture [2
]. Hip fractures are the most important consequence of osteoporosis; they require hospital admission and are associated with an excess mortality of 10–20% in the first year after the fracture [3
]. In white women the one in six lifetime risk of hip fracture is greater than the one in nine risk of developing breast cancer [4
]. The annual cost of all osteoporotic fractures to the United States has been estimated as $20 billion and to the European Union as $30 billion [5
Osteoporotic fracture is a result of a combination of an injury generating a given force, and bone strength weak enough to fracture at that force. An established measure of bone strength is bone mass, which is a composite of bone size and bone volumetric mineral density [6
]. The DXA derived measurements which contribute to bone mass are thus bone mineral content (BMC, g), bone area (BA, cm2
), bone mineral density (BMD, g/cm2
). True volumetric BMD (vBMD, g/cm3
) cannot be directly measured by DXA, although estimates can be obtained by adjusting for body size.
Bone mass appears to track through childhood and adolescence to reach a peak in early adulthood, more through an increase of bone size than true volumetric density [7
]. It then declines in older age, through loss of bone tissue (thinning of trabeculae and cortex), with an accelerated rate of decline at the menopause. Prospective studies in adults indicate that the risk of osteoporotic fracture increases continuously as BMD declines, with a 1.5–3 fold increase in the risk of osteoporotic fracture for each standard deviation fall in BMD [8
]. The ability to predict fracture risk from BMD is at least as good, if not better, than the ability to predict heart disease from blood cholesterol levels, and stroke from blood pressure [9
Preventative strategies against osteoporosis can be aimed at either optimizing the peak bone mass obtained, or reducing the rate of bone loss. Optimization of peak bone mass may be more amenable to public health strategies and has been shown in mathematical models to be a powerful predictor of age of onset of osteoporosis [6
]. Although this crucial characteristic is partly inherited, the currently identified genetic markers only explain a small amount of the variation in individual peak bone mass and fracture risk [11
]. Evidence is accruing that environmental factors may act early in development (in utero and early postnatal life), interacting with the genome to produce a persisting influence on postnatal skeletal development.