{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T01:45:43Z","timestamp":1779241543355,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies have demonstrated a correlation between thyroid dysfunction and osteoporosis (OP); however, the underlying causality has yet to be fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The necessary dataset was sourced from public databases. Initially, instrumental variables (IVs) were selected based on three primary hypotheses. Subsequently, Cochran\u2019s Q test was employed to exclude IVs exhibiting heterogeneity. The MR-PRESSO test and the leave-one-out sensitivity test were further applied to detect potential pleiotropy. Inverse variance was utilized for the analysis. This study primarily utilized the inverse variance weighted (IVW) model for Mendelian analysis. Since Type 1 diabetes mellitus can also contribute to the development of osteoporosis, this study additionally employed multivariate Mendelian analysis. Furthermore, 249 circulating metabolites were selected for mediation analysis in the Mendelian randomization framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, the two-sample Mendelian randomization (MR) analysis primarily employed the random-effects IVW model and demonstrated a causal relationship between hypothyroidism (OR\u2009=\u20091.092, 95% CI: 1.049\u20131.137, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) and hyperthyroidism (OR\u2009=\u20091.080, 95% CI: 1.026\u20131.137, <jats:italic>p<\/jats:italic>\u2009=\u20090.003) with the risk of OP. No causal relationships were identified between FT3, FT4, TSH, and the risk of OP (<jats:italic>p<\/jats:italic>\u2009&amp;gt;\u20090.05). The results of the multivariate Mendelian randomization (MVMR) analysis indicated that hyperthyroidism was no longer a risk factor for OP (OR\u2009=\u20090.984, 95% CI: 0.918\u20131.055, <jats:italic>p<\/jats:italic>\u2009=\u20090.657), whereas hypothyroidism persisted as a risk factor (OR\u2009=\u20091.082, 95% CI: 1.021\u20131.147, <jats:italic>p<\/jats:italic>\u2009=\u20090.008). The mediated Mendelian randomization analysis revealed that hypothyroidism may exert an indirect effect on OP via triglycerides in large VLDL, mediating approximately 2.47% of the effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identifies a potential link between hypothyroidism and OP, possibly mediated indirectly via triglyceride levels in large VLDL. Further investigations are required to elucidate the direct or indirect causal mechanisms underlying this association.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1453502","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T14:35:28Z","timestamp":1730471728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Hypothyroidism correlates with osteoporosis: potential involvement of lipid mediators"],"prefix":"10.3389","volume":"11","author":[{"given":"Pengyuan","family":"Leng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengxue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingming","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weili","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1359\/jbmr.061113","article-title":"Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025","volume":"22","author":"Burge","year":"2007","journal-title":"J Bone Miner Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.ygeno.2018.05.001","article-title":"New insights into the epigenetics of osteoporosis","volume":"111","author":"Letarouilly","year":"2019","journal-title":"Genomics"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"9465","DOI":"10.3390\/ijms23169465","article-title":"Current status of the diagnosis and Management of Osteoporosis","volume":"23","author":"Aibar-Almaz\u00e1n","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1007\/s00198-021-05900-y","article-title":"The clinician's guide to prevention and treatment of osteoporosis","volume":"33","author":"Leboff","year":"2022","journal-title":"Osteoporos Int"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/bmb\/ldr030","article-title":"The epidemiology of thyroid disease","volume":"99","author":"Vanderpump","year":"2011","journal-title":"Br Med Bull"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1007\/s00198-019-05205-1","article-title":"Subclinical thyroid dysfunction, bone mineral density, and osteoporosis in a middle-aged Korean population","volume":"31","author":"Lee","year":"2020","journal-title":"Osteoporos Int"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"908831","DOI":"10.3389\/fimmu.2022.908831","article-title":"Systemic lupus erythematosus and cardiovascular disease: a Mendelian randomization study","volume":"13","author":"Gao","year":"2022","journal-title":"Front Immunol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.jdiacomp.2015.12.027","article-title":"Incidence and prevalence of thyroid dysfunction in type 1 diabetes","volume":"30","author":"Nederstigt","year":"2016","journal-title":"J Diabetes Complicat"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/s41580-019-0108-4","article-title":"Identification of bioactive metabolites using activity metabolomics","volume":"20","author":"Rinschen","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1152\/physrev.00035.2018","article-title":"Metabolomics for investigating physiological and pathophysiological processes","volume":"99","author":"Wishart","year":"2019","journal-title":"Physiol Rev"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1210\/clinem\/dgac555","article-title":"Plasma metabolomics reveals systemic metabolic alterations of subclinical and clinical hypothyroidism","volume":"108","author":"Shao","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"901786","DOI":"10.3389\/fcvm.2022.901786","article-title":"Elucidating the relationship between dyslipidemia and osteoporosis: a multicenter, prospective cohort study protocol","volume":"9","author":"Wei","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"853889","DOI":"10.3389\/fendo.2022.853889","article-title":"Menopausal impact on the association between thyroid dysfunction and lipid profiles: a cross-sectional study","volume":"13","author":"Han","year":"2022","journal-title":"Front Endocrinol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"4913","DOI":"10.1093\/eurheartj\/ehad736","article-title":"Mendelian randomization for cardiovascular diseases: principles and applications","volume":"44","author":"Larsson","year":"2023","journal-title":"Eur Heart J"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1007\/s10654-018-0424-6","article-title":"Mendelian randomization with a binary exposure variable: interpretation and presentation of causal estimates","volume":"33","author":"Burgess","year":"2018","journal-title":"Eur J Epidemiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3389\/fgene.2020.00157","article-title":"LdlinkR: an R package for rapidly calculating linkage disequilibrium statistics in diverse populations","volume":"11","author":"Myers","year":"2020","journal-title":"Front Genet"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1093\/ije\/dyx002","article-title":"Pleiotropy-robust Mendelian randomization","volume":"47","author":"Van Kippersluis","year":"2018","journal-title":"Int J Epidemiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1186\/s13054-023-04763-5","article-title":"Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study","volume":"27","author":"Li","year":"2023","journal-title":"Crit Care"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1285106","DOI":"10.3389\/fimmu.2023.1285106","article-title":"Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional mendelian-randomization study","volume":"14","author":"Fang","year":"2023","journal-title":"Front Immunol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e1009922","DOI":"10.1371\/journal.pgen.1009922","article-title":"Combining the strengths of inverse-variance weighting and egger regression in Mendelian randomization using a mixture of regressions model","volume":"17","author":"Lin","year":"2021","journal-title":"PLoS Genet"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1096519","DOI":"10.3389\/fpubh.2023.1096519","article-title":"Effect of basal metabolic rate on osteoporosis: a Mendelian randomization study","volume":"11","author":"Zhou","year":"2023","journal-title":"Front Public Health"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1007\/s00784-023-04874-x","article-title":"Association between periodontitis and breast cancer: two-sample Mendelian randomization study","volume":"27","author":"Ding","year":"2023","journal-title":"Clin Oral Investig"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2188\/jea.JE20220154","article-title":"Bmi and Cardiometabolic traits in Japanese: a Mendelian randomization study","volume":"34","author":"Nagayoshi","year":"2024","journal-title":"J Epidemiol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The Mr-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"elife"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41597-023-01949-y","article-title":"Quality control and removal of technical variation of Nmr metabolic biomarker data in ~120,000 Uk biobank participants","volume":"10","author":"Ritchie","year":"2023","journal-title":"Sci Data"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s10654-021-00757-1","article-title":"Mendelian randomisation for mediation analysis: current methods and challenges for implementation","volume":"36","author":"Carter","year":"2021","journal-title":"Eur J Epidemiol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1037\/1082-989X.7.1.83","article-title":"A comparison of methods to test mediation and other intervening variable effects","volume":"7","author":"Mackinnon","year":"2002","journal-title":"Psychol Methods"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e10838","DOI":"10.1002\/jbm4.10838","article-title":"Antiresorptive versus anabolic therapy in managing osteoporosis in people with type 1 and type 2 diabetes","volume":"7","author":"Vilaca","year":"2023","journal-title":"Jbmr Plus"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12916-022-02376-3","article-title":"Temporal relationship among adiposity, gut microbiota, and insulin resistance in a longitudinal human cohort","volume":"20","author":"Deng","year":"2022","journal-title":"BMC Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1177\/0004563218759371","article-title":"The bone remodelling cycle","volume":"55","author":"Kenkre","year":"2018","journal-title":"Ann Clin Biochem"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"859","DOI":"10.2174\/1871530320666200810144506","article-title":"Low Normal Tsh levels and thyroid autoimmunity are associated with an increased risk of osteoporosis in Euthyroid postmenopausal women","volume":"21","author":"Yang","year":"2021","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"ref32","first-page":"57","article-title":"Thyroid dysfunction in an adult female population: a population-based study of Latin American vertebral osteoporosis study (Lavos) - Puerto Rico site","volume":"32","author":"Gonz\u00e1lez-Rodr\u00edguez","year":"2013","journal-title":"P R Health Sci J"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12902-021-00715-8","article-title":"Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation","volume":"21","author":"Deng","year":"2021","journal-title":"BMC Endocr Disord"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1210\/jc.2013-2474","article-title":"Thyrotropin levels within the lower normal range are associated with an increased risk of hip fractures in euthyroid women, but not men, over the age of 65 years","volume":"99","author":"Leader","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/cen.13615","article-title":"Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men","volume":"89","author":"Siru","year":"2018","journal-title":"Clin Endocrinol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"104","DOI":"10.25122\/jml-2021-0297","article-title":"Biochemical changes in patients during hypothyroid phase after thyroidectomy","volume":"15","author":"Al-Janabi","year":"2022","journal-title":"J Med Life"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"792536","DOI":"10.3389\/fendo.2021.792536","article-title":"Plasma lipid profile and intestinal microflora in pregnancy women with hypothyroidism and their correlation with pregnancy outcomes [J]","volume":"12","author":"Cai","year":"2021","journal-title":"Front Endocrinol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s00223-023-01160-6","article-title":"Lipid metabolism, methylation aberrant, and osteoporosis: a multi-omics study based on Mendelian randomization","volume":"114","author":"Zhang","year":"2024","journal-title":"Calcif Tissue Int"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"116703","DOI":"10.1016\/j.bone.2023.116703","article-title":"Association of insulin resistance with bone mineral density in a nationwide health check-up population in China","volume":"170","author":"Zhuo","year":"2023","journal-title":"Bone"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1453502\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T14:35:30Z","timestamp":1730471730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1453502\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":39,"alternative-id":["10.3389\/fmed.2024.1453502"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1453502","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,1]]},"article-number":"1453502"}}