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Gene variants linked to increased fracture risk

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Gene variants of lipoprotein receptor-related protein 5 are associated with a consistent increase in the risk of fractures and lower levels of bone mineral density.

Researchers from The Netherlands, the United States and other sites conducted a prospective, multicenter, collaborative study of 37,534 participants from 18 teams in Europe and North America. They aimed to determine whether two variants of LRP5 (Val667Met, Ala1330Val) and one variant of LRP6 (lle1062Val) are associated with BMD and fracture risk.

Reduced lumbar spine BMD was associated with both LRP5 alleles. Similar results were found for femoral neck BMD and both alleles were associated with vertebral fractures. The risk for all fractures was increased with both Met667 (OR, 1.14; 7,876 fractures among 31,435 individuals) and Val1330 (OR, 1.06; 7,802 fractures among 31,199 individuals).

Despite adjustments made for age, weight, height, menopausal status and hormone therapy use, results remained similar. According to the researchers, the LRP6 lle1062Val polymorphism was not linked to any osteoporosis phenotype. – by Stacey L. Adams

JAMA. 2008;299:1277-1290.