Bone mineral density (BMD) is under genetic control. Some studies in Caucasian and Asian women suggest that polymorphisms in the vitamin D receptor (VDR) gene are associated with BMD and the rate of postmenopausal bone loss. We determined if similar associations exist in 101 African-American women aged 65 years and older (71 +/- 5 years, mean +/- SD). We also examined the relation between VDR genotype and fractional 45Ca absorption and markers of bone formation (osteocalcin) and resorption (N-telopeptides) in these women. BMD was measured at the proximal femur and whole body at baseline and after 1.9 +/- 0.4 years (femur only) on a Hologic QDR-2000 densitometer using dual-energy X-ray absorptiometry. Calcaneal BMD was measured with single x-ray absorptiometry. VDR gene polymorphisms were defined by the endonucleases BsmI, ApaI, and TaqI. These polymorphisms were not associated with BMD at any skeletal site or with markers of bone turnover. There was a significant interaction between age and VDR genotype where the oldest women (> 70 years) with the TT genotype experienced greater hip bone loss than women with the TT genotype (-2.1%/year vs. -0.4%/year, respectively), whereas heterozygous women experienced an intermediate rate of bone loss (-1.3%/year). Women homozygous for the B allele had 14% lower fractional 45Ca absorption compared with women homozygous for the b allele, although this difference was not statistically significant (p = 0.08). We conclude that VDR gene polymorphisms are not associated with BMD or indices of bone turnover in this population of older African-American women. However, DNA sequence variation in the VDR gene or a nearby locus may influence intestinal calcium transport and the rate of postmenopausal bone loss in African-American women.