Osteoporosis is a major problem in all aging communities world-wide. Some major causes have been identified, such as bone loss associated with menopause and corticosteroid excess. However, lower peak bone density places any individual at increased risk for normal bone loss with age. Although some environmental factors have been identified, these contribute to a relatively small extent when compared with inherited factors. Although predisposition to falls is another important component of osteoporotic risk, the major bone-related factor is bone density. Because inherited factors determine perhaps 60% to 70% of the variance in bone density at any age, recent work has focused on genetic factors. Mutations in the procollagen type I gene, as in osteogenesis imperfecta and as recently reported in the estrogen receptor gene, are models of extreme changes in certain proteins, resulting in low bone density. Rather than focus on these probably rare mutations, many investigators have focused on common allelic variations in the vitamin D receptor gene. Despite some negative studies, there is now evidence from a variety of studies in different racial and ethnic groups that there are significant differences in bone density and there is a change in bone density over time associated with these allelic variants. This paper reviews the genetic factors in osteoporosis and the recent advances linking these associations to particular genes, in particular the common allelic variants in the vitamin D receptor gene.
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