In the present Study, we tested the association between the estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes with bone mineral density (BMD). A total of 649 healthy Chinese women, classified as pre-menopausal (N = 388) and post-menopausal (N = 261) groups, were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI sites. BMDs at the lumbar spine (L-1-L-4) and total hip were measured by dual-energy X-ray absorptiometry. For the VDR ApaI locus, AA carriers had lower spine BNID than Aa (p = 0.02) and aa carriers (p < 0.01) in the pre-menopausal group. For the ER-alpha gene, carriers of haplotype px had lower spine BMD than the non-carriers (p = 0.03) in the pre-menopausal group. Furthermore, we observed significant interaction between the ER-a and VDR genes in the post-menopausal group: with AA genotype (or A allele) at the VDR ApaI locus, pX carriers had higher spine BNID than the non-carriers (p = 0.02), and PX carriers had lower hip BNID than the non-carriers (p = 0.04). Our data suggest that the ER-alpha and VDR genes may be associated with the BMD variation in Chinese women. (C) 2003 Elsevier Inc. All rights reserved.