Osteoprotegerin (OPG) plays an important role in the osteoclast differentiation as an effective inhibitor of osteoclast maturation and activation. We examined a potential effect of A163G single nucleotide polymorphism in the promoter region of the OPG gene on femoral neck (FN-BMD) and lumbar spine BMD (LS-BMD), as well as circulating alkaline phosphatase, osteocalcin (ALP, OC; formation markers), beta-CrossLaps (CTx; resorption marker) in Slovak postmenopausal women. In addition, fractures of spine, radius and femur were examined.Altogether 284 women (62.28 ± 8.40 years) were selected according to strict inclusion criteria. The polymorphism was detected by PCR-RFLP method. Genotype frequencies were tested using the chi-square test. The differences of quantitative variables between the genotypes were analyzed by covariance analysis (GLM procedure) after correction of the measurements for age and BMI. Fracture incidence in association with OPG genotype was evaluated by Binary Logistic Regression with the genotype, age, and BMI as covariates. The frequencies of genotypes were 76.8 %, 21.1 %, and 2.1 % for AA, AG, and GG, respectively. Statistically significant associations of OPG genotypes with FN-BMD (p < 0.01) and LS-BMD (p < 0.05) were observed. The GG genotype was associated with higher BMD values likewise decreased CTx concentration (p < 0.05) in compared with the other genotypes, which indicates that the allele G has a protective effect on bone. These associations were not followed by the effect of OPG on fracture incidence. Our results suggest that OPG/A163G polymorphism could contribute to the genetic regulation of BMD or bone turnover markers in Slovak population and thus could increase or decreased osteoporosis risk.