Genetic epidemiology of osteoporosis: past, present, and future.

Research during the past several decades has unequivocally established a role of heredity in the etiology of osteoporosis. Major efforts are currently underway to identify the genes and allelic variants that confer genetic susceptibility to this common and disabling condition. Genome-wide linkage mapping in families, candidate gene association studies in unrelated individuals, and quantitative trait locus mapping in animal models are the primary strategies being used to search for the genetic contributors to osteoporosis. Genome-wide mapping efforts have identified the low-density lipoprotein receptor-related protein 5, bone morphogenetic protein 2, and 15-lipoxygenase as potential susceptibility genes for osteoporosis in the past few years, providing a rich new base for understanding bone biology. Candidate gene association analyses have also provided evidence for a modest role of allelic variants in several additional genes including collagen type Ialpha1, vitamin D receptor, and estrogen receptor-alpha. With the development of a high-density genome-wide polymorphism and haplotype map and continued improvements in high-throughput and cost-effective genotyping technologies, many more genetic contributors to osteoporosis will probably be identified in the near future. The results of this research should facilitate the development of new methods for diagnosing, preventing, and treating the growing clinical and public health problem of osteoporosis.