To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.