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Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis

INTRODUCTION: 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 iden...

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Autores principales: Marozik, Pavel, Alekna, Vidmantas, Rudenko, Ema, Tamulaitiene, Marija, Rudenka, Alena, Mastaviciute, Asta, Samokhovec, Volha, Cernovas, Andrejus, Kobets, Katsiaryna, Mosse, Irma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705789/
https://www.ncbi.nlm.nih.gov/pubmed/31437227
http://dx.doi.org/10.1371/journal.pone.0221511
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author Marozik, Pavel
Alekna, Vidmantas
Rudenko, Ema
Tamulaitiene, Marija
Rudenka, Alena
Mastaviciute, Asta
Samokhovec, Volha
Cernovas, Andrejus
Kobets, Katsiaryna
Mosse, Irma
author_facet Marozik, Pavel
Alekna, Vidmantas
Rudenko, Ema
Tamulaitiene, Marija
Rudenka, Alena
Mastaviciute, Asta
Samokhovec, Volha
Cernovas, Andrejus
Kobets, Katsiaryna
Mosse, Irma
author_sort Marozik, Pavel
collection PubMed
description INTRODUCTION: 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 SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 gene variants on the response to treatment with aminobisphosphonates. MATERIALS AND METHODS: Women with postmenopausal osteoporosis were included to this study if they used aminobisphosphonates 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 SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). RESULTS: 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 SOST rs1234612 T/T (OR = 2.3; P = 0.02), PTH rs7125774 T/T (OR = 2.8, P = 0.0009), FDPS rs2297480 G/G (OR = 29.3, P = 2.2×10(−7)), and GGPS1 rs10925503 C/C+C/T (OR = 2.9; P = 0.003) gene variants were over-represented in non-responders group. No significant association between FGF2 rs6854081 and LRP5 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). CONCLUSIONS: 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.
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spelling pubmed-67057892019-09-04 Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis Marozik, Pavel Alekna, Vidmantas Rudenko, Ema Tamulaitiene, Marija Rudenka, Alena Mastaviciute, Asta Samokhovec, Volha Cernovas, Andrejus Kobets, Katsiaryna Mosse, Irma PLoS One Research Article INTRODUCTION: 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 SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 gene variants on the response to treatment with aminobisphosphonates. MATERIALS AND METHODS: Women with postmenopausal osteoporosis were included to this study if they used aminobisphosphonates 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 SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). RESULTS: 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 SOST rs1234612 T/T (OR = 2.3; P = 0.02), PTH rs7125774 T/T (OR = 2.8, P = 0.0009), FDPS rs2297480 G/G (OR = 29.3, P = 2.2×10(−7)), and GGPS1 rs10925503 C/C+C/T (OR = 2.9; P = 0.003) gene variants were over-represented in non-responders group. No significant association between FGF2 rs6854081 and LRP5 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). CONCLUSIONS: 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. Public Library of Science 2019-08-22 /pmc/articles/PMC6705789/ /pubmed/31437227 http://dx.doi.org/10.1371/journal.pone.0221511 Text en © 2019 Marozik et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Marozik, Pavel
Alekna, Vidmantas
Rudenko, Ema
Tamulaitiene, Marija
Rudenka, Alena
Mastaviciute, Asta
Samokhovec, Volha
Cernovas, Andrejus
Kobets, Katsiaryna
Mosse, Irma
Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
title Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
title_full Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
title_fullStr Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
title_full_unstemmed Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
title_short Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
title_sort bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705789/
https://www.ncbi.nlm.nih.gov/pubmed/31437227
http://dx.doi.org/10.1371/journal.pone.0221511
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