Objectives: To explore the influence of 14 single nucleotide polymorphisms (SNPs) in receptor activator of nuclear factor-kappa B (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) on bone mineral density (BMD) in a Chinese female population. Design and methods: A cross-sectional study was conducted in 108 perimenopausal and 127 postmenopausal women aged 43-65 years. All participants underwent lumbar spinal and nondominant femoral BMD evaluation by dual energy X-ray absorptiometry. Fourteen RANK, RANKL and OPG genotypes were determined by chip-based MALDI-TOF mass spectrometry. The differences between the BMDs of the RANK genotypes were analyzed. Results: Five SNPs (rs6993813, rs4355801, rs1032129 and rs2073618 in OPG and rs3018362 in RANK) were significantly associated with BMD or with BMD adjusted for body weight or years since menopause, mostly at the femoral neck but also partly at the total hip (p < 0.05). The risk allele frequencies observed in our sample were different from those found in Europeans but the effects of these risk alleles on BMD values had the same direction in our cohort as in Europeans, except for rs3018362 with G as the risk allele, which was contrary to other studies. None of the SNPs in RANKL were associated with BMD at any anatomical site. Conclusions: Our findings suggest that OPG and RANK but not RANKL genetic polymorphisms influence BMD mainly in the femoral neck in peri- and postmenopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health. (c) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.