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Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study

Pathological excess of fibroblast growth factor 23 (FGF23) causes mineral and bone disorders. However, the causality of FGF23 in the development of osteoporosis remains unknown. Whether FGF23 has systemic effects on cardio-metabolic disorders beyond regulating mineral metabolism is also controversia...

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Autores principales: Yokomoto-Umakoshi, Maki, Umakoshi, Hironobu, Miyazawa, Takashi, Ogata, Masatoshi, Sakamoto, Ryuichi, Ogawa, Yoshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089954/
http://dx.doi.org/10.1210/jendso/bvab048.552
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author Yokomoto-Umakoshi, Maki
Umakoshi, Hironobu
Miyazawa, Takashi
Ogata, Masatoshi
Sakamoto, Ryuichi
Ogawa, Yoshihiro
author_facet Yokomoto-Umakoshi, Maki
Umakoshi, Hironobu
Miyazawa, Takashi
Ogata, Masatoshi
Sakamoto, Ryuichi
Ogawa, Yoshihiro
author_sort Yokomoto-Umakoshi, Maki
collection PubMed
description Pathological excess of fibroblast growth factor 23 (FGF23) causes mineral and bone disorders. However, the causality of FGF23 in the development of osteoporosis remains unknown. Whether FGF23 has systemic effects on cardio-metabolic disorders beyond regulating mineral metabolism is also controversial. In this study, we evaluated the causal effect of FGF23 on osteoporosis and cardiometabolic disorders using Mendelian randomization (MR) analysis. Summary statistics for single-nucleotide polymorphisms with traits of interest were obtained from the relevant genome-wide association studies. As a result, FGF23 was found to be inversely associated with femoral neck-BMD (odds ratio [OR] 0.682, 95% confidence interval [CI] 0.546–0.853, p = 8e-04) and heel estimated BMD (eBMD) (OR 0.898, 95%CI 0.820–0.985, p = 0.022) in the inverse-variance-weighted analysis, but not lumbar spine-BMD and fractures. The results were supported by the weighted-median analysis, and there was no evidence of pleiotropy in the MR-Egger analysis. FGF23 was directly associated with FN-BMD and eBMD after adjustment for estimated glomerular filtration rate, height, and body mass index in multivariable MR analysis. On the other hand, there was no association between FGF23 and cardiometabolic traits including cardio artery disease, brachial-ankle pulse wave velocity, intima-media thickness of carotid arteries, systolic and diastolic blood pressure, fasting glucose, high and low-density lipoprotein cholesterol, and triglycerides. Therefore, FGF23 has been causally associated with bone loss. In contrast, FGF23 has not been causally associated with cardiometabolic disorders. The data of this study provides important insights into the role of FGF23 in the pathogenesis of osteoporosis and cardiometabolic disorders.
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spelling pubmed-80899542021-05-06 Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study Yokomoto-Umakoshi, Maki Umakoshi, Hironobu Miyazawa, Takashi Ogata, Masatoshi Sakamoto, Ryuichi Ogawa, Yoshihiro J Endocr Soc Bone and Mineral Metabolism Pathological excess of fibroblast growth factor 23 (FGF23) causes mineral and bone disorders. However, the causality of FGF23 in the development of osteoporosis remains unknown. Whether FGF23 has systemic effects on cardio-metabolic disorders beyond regulating mineral metabolism is also controversial. In this study, we evaluated the causal effect of FGF23 on osteoporosis and cardiometabolic disorders using Mendelian randomization (MR) analysis. Summary statistics for single-nucleotide polymorphisms with traits of interest were obtained from the relevant genome-wide association studies. As a result, FGF23 was found to be inversely associated with femoral neck-BMD (odds ratio [OR] 0.682, 95% confidence interval [CI] 0.546–0.853, p = 8e-04) and heel estimated BMD (eBMD) (OR 0.898, 95%CI 0.820–0.985, p = 0.022) in the inverse-variance-weighted analysis, but not lumbar spine-BMD and fractures. The results were supported by the weighted-median analysis, and there was no evidence of pleiotropy in the MR-Egger analysis. FGF23 was directly associated with FN-BMD and eBMD after adjustment for estimated glomerular filtration rate, height, and body mass index in multivariable MR analysis. On the other hand, there was no association between FGF23 and cardiometabolic traits including cardio artery disease, brachial-ankle pulse wave velocity, intima-media thickness of carotid arteries, systolic and diastolic blood pressure, fasting glucose, high and low-density lipoprotein cholesterol, and triglycerides. Therefore, FGF23 has been causally associated with bone loss. In contrast, FGF23 has not been causally associated with cardiometabolic disorders. The data of this study provides important insights into the role of FGF23 in the pathogenesis of osteoporosis and cardiometabolic disorders. Oxford University Press 2021-05-03 /pmc/articles/PMC8089954/ http://dx.doi.org/10.1210/jendso/bvab048.552 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Bone and Mineral Metabolism
Yokomoto-Umakoshi, Maki
Umakoshi, Hironobu
Miyazawa, Takashi
Ogata, Masatoshi
Sakamoto, Ryuichi
Ogawa, Yoshihiro
Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study
title Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study
title_full Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study
title_fullStr Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study
title_full_unstemmed Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study
title_short Causal Effect of Fibroblast Growth Factor 23 on Osteoporosis and Cardiometabolic Disorders: A Mendelian Randomization Study
title_sort causal effect of fibroblast growth factor 23 on osteoporosis and cardiometabolic disorders: a mendelian randomization study
topic Bone and Mineral Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089954/
http://dx.doi.org/10.1210/jendso/bvab048.552
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