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Background  The study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene ( ESR1 ) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia.    Methods  We analysed 343 postmenopausal Slovak women (62.40 ± 0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs. TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both;  N  = 76) or SERMs/raloxifene (60 mg/day;  N  = 64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements.    Results  Women with AA genotype of rs9340799 had higher BMD-FN (+ 0.12 ± 0.57 of T-score) and BMD-LS (+ 0.17 ± 0.08 of T-score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any  ESR1  polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the  ESR1  gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (− 0.26 ± 0.10 of BMD-FN T-score; − 0.35 ± 0.10 of BMD-LS T-score) and also with AG genotype (− 0.22 ± 0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (− 0.22 ± 0.08 of T-score) and CC (− 0.35 ± 0.09 of T-score). The effect of the  ESR1  gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a − 0.30 ± 0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed − 0.39 ± 0.11 and − 0.46 ± 0.15 lower T-scores in comparison with TC and CC genotypes, respectively.    Conclusions  The rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.    Electronic supplementary material  The online version of this article (10.1186/s12881-018-0684-8) contains supplementary material, which is available to authorized users.

The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women