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Osteoporosis may be defined as a reduction in bone mineral density (BMD) of at least 2.5 standard deviations (SD) accompanied by microarchitectural changes and increased bone fragility (Schapira & Schapira, 1992). Genetic studies of osteoporosis have principally focused on the first part of this definition, BMD heritability, due to the large patient populations required for genetic analyses and the relative ease with which BMD measurements can now be obtained. From a public health perspective, however, bone fragility is of critical importance and thus increasing attention is being devoted to the genetics of fracture risk. Integral to any discussion of BMD and bone strength is the issue of bone loss. It is the genetics of these key determinants of progression to osteoporosis, the genetics of bone mass, bone loss and bone fragility, that form the subject matter for this chapter (Fig. 10.1).
Genetics of BMD — a quantitative trait
Like serum sodium or arterial blood pressure, bone mineral density values lie along a continuum; thus BMD is termed a quantitative trait. Genetic studies of quantitative traits are difficult to perform since family members cannot be neatly divided into affected and unaffected categories, as can be done with Mendelian (single gene) disorders.
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