VITAMIN-D-RECEPTOR GENOTYPE AND THE RISK OF BONE-FRACTURES IN WOMEN

Several studies have confirmed an initial report of a relation between bone density and polymorphic forms of the calcitriol (vitamin D) rece ptor gene, whereas others have failed to find an association. We exami ned whether variants of the vitamin D receptor gene are associated wit h the risk of bone fracture, using a nested case-control analysis with in the Nurses' Health Study cohort. The study women all were Caucasian and were 43-69 years of age when they provided a blood sample. Cases included the 54 proximal femur (hip) fractures and 163 distal radius ( forearm) fractures that occurred subsequent to the blood draw. Cases a nd controls were genotyped by polymerase chain reaction for the BsmI p olymorphism. The BE genotype, previously associated with lower bone de nsity, was associated with a more than twofold increased risk of hip f racture compared with the bb genotype. Risk was greater for women who were older, leaner, or less physically active or who had a lower calci um intake. The heterozygous genotype was not associated with any incre ased risk of hip fracture, and we observed little association between vitamin D receptor genotype and forearm fracture. This study supports an association between vitamin D receptor genotype and hip fracture. I t also implies that modification by other risk factors may have contri buted to the conflicting results from previous studies of vitamin D re ceptor genotype and femoral bone density.