Osteoporosis is a disease characterized by fragile bones and high susceptibility to low-trauma fractures. It is a serious health problem, especially in elderly women. Bone mineral density (BMD) has been employed most commonly as the index for defining and studying osteoporosis. BMD has high genetic determination, with heritability ranging from 50 to 90%. Various gene-mapping approaches have been applied to identify specific genes underlying osteoporosis, largely using BMD as the study phenotype. We review here the genetic determination of osteoporosis as defined by BMD and discuss a fundamental issue we encounter in genetic research in osteoporosis: the choice of phenotype(s) to study. We briefly summarize and discuss advantages and disadvantages of various approaches used in genetic studies of osteoporosis. Finally, we review and discuss the current status for mapping and identification of genes for osteoporosis. We focus on linkage studies in humans and quantitative trait loci mapping in mice to supplement the already extensive reviews of association studies made by many investigators for candidate genes.
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