DOI: 10.5281/zenodo.3354118
title: Bone metabolism gene variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis

description: This repository contains the raw and source data for the manuscript "Bone metabolism gene polymorphism and response to bisphosphonate treatment in women with postmenopausal osteoporosis" submitted to PLOS ONE. <strong>Abstract: </strong> <em>Introduction:</em> Long-term treatment is used in patients with osteoporosis, and bisphosphonates (BPs) are the most commonly prescribed medications. However, in some patients this therapy is not effective, cause different side effects and complications. Unfortunately, at least one year is needed to identify and confirm an ineffectiveness of BPs therapy on bone mineral density (BMD). Among other factors, a response to BPs therapy may also be explained by genetic factors. The aim of this study was to analyze the influence of <em>SOST, PTH, FGF2, FDPS, GGPS1, </em>and<em> LRP5</em> gene polymorphisms on the response to treatment with BPs. <em>Materials and methods: </em>Women with postmenopausal osteoporosis were included to this study if they used bisphosphonates for at least 12 months. Exclusion criteria were: persistence on BPs therapy less than 80%, bone metabolic diseases, diseases deemed to affect bone metabolism, malignant tumours, using of any medications influencing BMD. The study protocol was approved by the local ethics committee. The BMD at the lumbar spine and femoral neck were measured using dual x-ray absorptiometry (GE Lunar) before and at least 12 months after treatment with BPs. According to BMD change, patients were divided in two groups – responders and non-responders to BPs terapy. Polymorphic variants in <em>SOST, PTH, FGF2, FDPS, GGPS1, </em>and<em> LRP5</em> genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). <em>Results:</em> In total, 201 women with BPs therapy were included in the study. No statistically significant differences were observed in age, age at menopause, weight, height, BMI and baseline BMD levels between responders (122 subjects) and non-responders (79 subjects). As single markers, the <em>SOST </em>rs1234612 T/T (OR=2.3; P=0.02), <em>PTH</em> rs7125774 T/T (OR=2.8, P=0.0009), <em>FDPS</em> rs2297480 G/G (OR=29.3, P=2.2×10<sup>-7</sup>), and <em>GGPS1</em> rs10925503 C/C+C/T (OR=2.9; P=0.003) gene variants were over-represented in non-responders group. No significant association between <em>FGF2</em> rs6854081 and <em>LRP5</em> rs3736228 gene variants and response to BPs treatment was observed. The carriers of T-T-G-C allelic combination (constructed from rs1234612, rs7125774, rs2297480, and rs10925503) were predisposed to negative response to BPs treatment (OR = 4.9, 95% CI 1.7–14.6, P=0.005). The C-C-T-C combination was significantly over-represented in responders (OR = 0.1, 95% CI 0.1–0.5, P=0.006). <em>Conclusions:</em> Our findings highlight the importance of identified single gene variants and their allelic combinations for pharmacogenetics of BPs therapy of osteoporosis. Complex screening of these genetic markers could be used as a new strategy for personalized antiresorptive therapy.