VITAMIN-D-RECEPTOR ALLELES AND RATES OF BONE LOSS - INFLUENCES OF YEARS SINCE MENOPAUSE AND CALCIUM INTAKE

A genetic marker for the 1,25-dihydroxyvitamin D receptor (VDR) is rep orted to account for much of the heritable component of bone density. It is not known whether VDR genotype influences bone accretion or loss , or how it is related to calcium metabolism. The VDR genotype was det ermined in 229 healthy postmenopausal women who previously participate d in a calcium trial. VDR alleles were designated according to presenc e Cb) or absence (B) of the BsmI restriction enzyme cutting site. Ther e were 83 bb, 102 Bb, and 44 BB individuals. Two-thirds of the women t ook 500 mg of calcium supplement (mean calcium intake = 892 mg/day) an d one-third a placebo (mean = 376 mg/day). Bone mineral density (BMD) at the femoral neck, spine, and radius were measured by dual- and sing le-photon absorptiometry at baseline and after 1 and 2 years. Among wo men more than 10 years postmenopausal, those with the BE genotype had the lowest femoral neck BMD. Rates of bone loss over 2 years were grea ter in the BE group at all sites (e.g., at the femoral neck, bb, 0.45 +/- 0.43; Bb, -0.01 +/- 0.40; BB, -0.99 +/- 0.05%/year; BB vs. bb, p = 0.01), and this trend was found both in women <10 years since menopau se (e.g., at the radius, bb, 0.43 +/- 0.47; Bb, -0.37 +/- 0.42; BB, -1 .20 +/- 0.59% per year; BB vs. bb, p = 0.02) and those greater than or equal to 10 years (radius, bb, -0.71 +/- 0.41; Bb, 0.08 +/- 0.39; BB, -1.41 +/- 0.49% per year; BB vs. Bb, p < 0.01). At the femoral neck b one loss appeared to be modified by calcium intake (e.g., in the BE ge notype: +0.03 +/- 0.61 in supplemented vs. -2.01 a 0.75%/year in place bo, in bb: 0.57 +/- 0.58 vs. 0.32 +/- 0.47%/year; interaction term p = 0.09), and this trend was also present in both early and late menopau se. Rates of change at the radius and spine in BE were not significant ly influenced by calcium at the intake levels of this study group. The se results indicate that postmenopausal bone loss is influenced by the VDR genotype and suggest the adverse effect of the susceptible allele at the hip may be reduced by raising calcium intake.