Bone mass and its mineral content has been shown to be under genetic control. Our purpose in this study was to assess whether estrogen receptor genotypes influence changes in bone mass in post menopausal Japanese women and clarify the regional differences in Japanese women. Pvu II and Xba I restriction enzyme fragment length polymorphism of the estrogen receptor gene and its relationship with vertebral bone mineral density were examined in 300 unrelated post menopausal women, aged 42-69 years, from the Kinki region in Japan. Vertebral bone mineral density was evaluated at the lumbar spine (L2-4) by dual energy X-ray absorptiometry. We found no relationship between any single restriction site polymorphism and the Z-score of bone mineral density. However, the allelic haplotype PPXx was found to be associated with a significantly low bone mineral density (Z-score for the lumbar spine -1.118+/-1.270 vs. PPxx 0.04+/-1.150; p<0.01, vs. ppxx 0.387+/-1.226; p<0.05, respectively). We suggest that ER gene polymorphism is associated with low bone mineral density and that this partly explains the cause of post menopausal bone loss in Japanese women. The contradictory conclusions compared with previous studies in the Japanese population regarding the association of BMD with ER RFLPs demands further investigation.