{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:07:48Z","timestamp":1782835668276,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:00:00Z","timestamp":1703894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Scientific Research Foundation of the Education Department of the Province Anhui","award":["2022AH050653"],"award-info":[{"award-number":["2022AH050653"]}]},{"name":"Key Scientific Research Foundation of the Education Department of the Province Anhui","award":["2022xkj006"],"award-info":[{"award-number":["2022xkj006"]}]},{"name":"Natural Science Foundation of Anhui Medical University","award":["2022AH050653"],"award-info":[{"award-number":["2022AH050653"]}]},{"name":"Natural Science Foundation of Anhui Medical University","award":["2022xkj006"],"award-info":[{"award-number":["2022xkj006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>A number of studies from the literature have suggested that exposure to air pollutants is associated with a declined bone mineral density (BMD), and increased risks of osteoporosis (OP) and bone fractures. This study was performed to systemically assess the genetically causal associations of air pollutants with site-\/age-specific BMD and risk of bone fractures with the implementation of two-sample Mendelian randomization (TSMR) and multivariate Mendelian randomization (MVMR). The TSMR analysis was implemented to infer the causal associations between air pollutants and BMD and the risk of bone fractures, additional MVMR analysis was used to further estimate the direct causal effects between air pollutants and BMD, the occurrence of OP, and bone fractures. The results showed that NOx exposure contributed to lower femoral neck BMD (FN-BMD) (\u03b2 = \u22120.71, 95%CI: \u22121.22, \u22120.20, p = 0.006) and total body BMD (TB-BMD) (\u03b2 = \u22120.55, 95%CI: \u22120.90, \u22120.21, p = 0.002). Additionally, exposure to PM10 was found to be associated with a decreased TB-BMD (B \u03b2 = \u22120.42, 95%CI: \u22120.66, \u22120.18, p = 0.001), further age-specific subgroup analysis demonstrated the causal effect of PM10 exposure on the decreased TB-BMD in a subgroup aged 45 to 60 years (\u03b2 = \u22120.70, 95%CI: \u22121.12, \u22120.29, p = 0.001). Moreover, the findings of the MVMR analysis implied that there was a direct causal effect between PM10 exposure and the decreased TB-BMD (45 &lt; age &lt; 60), after adjusting for PM2.5 and PM2.5 \u201410 exposure. Our study provides additional evidence to support the causal associations of higher concentrations of air pollutant exposure with decreased BMD, especially in those populations aged between 45 to 60 years, suggesting that early intervention measures and public policy should be considered to improve public health awareness and promote bone health.<\/jats:p>","DOI":"10.3390\/toxics12010027","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T06:00:21Z","timestamp":1704002421000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Causal Relationships between Air Pollutant Exposure and Bone Mineral Density and the Risk of Bone Fractures: Evidence from a Two-Stage Mendelian Randomization Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Xiao","family":"Hu","sequence":"first","affiliation":[{"name":"Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"},{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Xing","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Ge","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Qing","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-5747","authenticated-orcid":false,"given":"Hai-Feng","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-682X","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"},{"name":"Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ITC17","DOI":"10.7326\/AITC201708010","article-title":"Osteoporosis","volume":"167","author":"Ensrud","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s00198-022-06454-3","article-title":"Global, Regional Prevalence, and Risk Factors of Osteoporosis According to the World Health Organization Diagnostic Criteria: A Systematic Review and Meta-Analysis","volume":"33","author":"Xiao","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ecl.2015.05.002","article-title":"Bone Health and Osteoporosis","volume":"44","author":"Lupsa","year":"2015","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1007\/BF01673403","article-title":"Age and Disease-Related Changes in the Mineral of Bone","volume":"53","author":"Grynpas","year":"1993","journal-title":"Calcif. Tissue Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.mayocp.2022.03.011","article-title":"Skeletal Aging","volume":"97","author":"Sfeir","year":"2022","journal-title":"Mayo Clin. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s10653-021-01129-0","article-title":"The Association between Hemoglobin Level and Osteoporosis in a Chinese Population with Environmental Lead and Cadmium Exposure","volume":"44","author":"Wang","year":"2022","journal-title":"Environ. Geochem. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100649","DOI":"10.1016\/j.cpcardiol.2020.100649","article-title":"Air Pollution and Cardiac Arrhythmias: A Comprehensive Review","volume":"46","author":"Shahrbaf","year":"2021","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.freeradbiomed.2020.01.004","article-title":"Oxidative Stress and the Cardiovascular Effects of Air Pollution","volume":"151","author":"Miller","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122181","DOI":"10.1016\/j.envpol.2023.122181","article-title":"Potential Roles of Air Pollutants on the Induction and Aggravation of Rheumatoid Arthritis: From Cell to Bedside Studies","volume":"334","author":"Gumtorntip","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e337","DOI":"10.1016\/S2542-5196(17)30136-5","article-title":"Association of Air Particulate Pollution with Bone Loss over Time and Bone Fracture Risk: Analysis of Data from Two Independent Studies","volume":"1","author":"Prada","year":"2017","journal-title":"Lancet Planet. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e733","DOI":"10.1097\/MD.0000000000000733","article-title":"Exposure to Air Pollution Increases the Risk of Osteoporosis: A Nationwide Longitudinal Study","volume":"94","author":"Chang","year":"2015","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/jrsm.1346","article-title":"Meta-Analysis and Mendelian Randomization: A Review","volume":"10","author":"Bowden","year":"2019","journal-title":"Res. Synth. Methods"},{"key":"ref_13","first-page":"a041302","article-title":"Mendelian Randomization","volume":"12","author":"Birney","year":"2022","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating Statistical Power in Mendelian Randomization Studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/biomet\/asx009","article-title":"Instrumental Variables as Bias Amplifiers with General Outcome and Confounding","volume":"104","author":"Ding","year":"2017","journal-title":"Biometrika"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/s41467-022-28294-9","article-title":"Assortative Mating Biases Marker-Based Heritability Estimators","volume":"13","author":"Border","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11195","DOI":"10.1021\/es301948k","article-title":"Development of Land Use Regression Models for PM(2.5), PM(2.5) Absorbance, PM(10) and PM(Coarse) in 20 European Study Areas; Results of the ESCAPE Project","volume":"46","author":"Eeftens","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian Randomization with Invalid Instruments: Effect Estimation and Bias Detection through Egger Regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nmeth.1974","article-title":"The 1000 Genomes Project: Data Management and Community Access","volume":"9","author":"Clarke","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding Bias from Weak Instruments in Mendelian Randomization Studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41586-019-1457-z","article-title":"Exome Sequencing of Finnish Isolates Enhances Rare-Variant Association Power","volume":"572","author":"Locke","year":"2019","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1038\/s41366-021-00817-2","article-title":"Genome-Wide Association Study of Neck Circumference Identifies Sex-Specific Loci Independent of Generalized Adiposity","volume":"45","author":"Liu","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11657-022-01061-5","article-title":"UK Clinical Guideline for the Prevention and Treatment of Osteoporosis","volume":"17","author":"Gregson","year":"2022","journal-title":"Arch. Osteoporos."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/gepi.21998","article-title":"Bias Due to Participant Overlap in Two-Sample Mendelian Randomization","volume":"40","author":"Burgess","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/biom.13169","article-title":"Approximation of Bias and Mean-Squared Error in Two-Sample Mendelian Randomization Analyses","volume":"76","author":"Deng","year":"2020","journal-title":"Biometrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s10654-015-0011-z","article-title":"Using Published Data in Mendelian Randomization: A Blueprint for Efficient Identification of Causal Risk Factors","volume":"30","author":"Burgess","year":"2015","journal-title":"Eur. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1021\/acs.analchem.2c03719","article-title":"Costs and Benefits of Popular P-Value Correction Methods in Three Models of Quantitative Omic Experiments","volume":"95","author":"Shuken","year":"2023","journal-title":"Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"a038984","DOI":"10.1101\/cshperspect.a038984","article-title":"Multivariable Mendelian Randomization and Mediation","volume":"11","author":"Sanderson","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/aje\/kwu283","article-title":"Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects","volume":"181","author":"Burgess","year":"2015","journal-title":"Am. J. Epidemiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/jrsm.13","article-title":"Critical Interpretation of Cochran\u2019s Q Test Depends on Power and Prior Assumptions about Heterogeneity","volume":"1","author":"Pereira","year":"2010","journal-title":"Res. Synth. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","first-page":"l6609","DOI":"10.1136\/bmj.l6609","article-title":"The Health Effects of Fine Particulate Air Pollution","volume":"367","author":"Loxham","year":"2019","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115327","DOI":"10.1016\/j.envpol.2020.115327","article-title":"Is Obesity the Missing Link between COVID-19 Severity and Air Pollution?","volume":"266","author":"Lubrano","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120699","DOI":"10.1016\/j.envpol.2022.120699","article-title":"Relationship of Multiple Metals Mixture and Osteoporosis in Older Chinese Women: An Aging and Longevity Study","volume":"317","author":"Feng","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1007\/s00198-007-0424-y","article-title":"Outdoor Air Pollution and Bone Mineral Density in Elderly Men\u2014The Oslo Health Study","volume":"18","author":"Alvaer","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101864","DOI":"10.1016\/j.eclinm.2023.101864","article-title":"Air Pollution and Decreased Bone Mineral Density among Women\u2019s Health Initiative Participants","volume":"57","author":"Prada","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"161117","DOI":"10.1016\/j.scitotenv.2022.161117","article-title":"Outdoor Air Pollution Exposure, Bone Mineral Density, Osteoporosis, and Osteoporotic Fractures: A Systematic Review and Meta-Analysis","volume":"865","author":"Mousavibaygei","year":"2023","journal-title":"Sci. Total. Environ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1153256","DOI":"10.3389\/fpubh.2023.1153256","article-title":"Risk of Ozone Exposure-Induced Fracture","volume":"11","author":"Lu","year":"2023","journal-title":"Front. Public. Health"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00198-021-06060-9","article-title":"Association between Exposure to Fine Particulate Matter and Osteoporosis: A Population-Based Cohort Study","volume":"33","author":"Adami","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1007\/s00198-017-4189-7","article-title":"Inflammatory Diseases and Bone Fragility","volume":"28","author":"Briot","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1152\/physrev.00033.2015","article-title":"Estrogens and Androgens in Skeletal Physiology and Pathophysiology","volume":"97","author":"Almeida","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/intimm\/dxq431","article-title":"IL-1 Plays an Important Role in the Bone Metabolism under Physiological Conditions","volume":"22","author":"Lee","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mrgentox.2008.10.005","article-title":"Air Pollutants, Oxidative Stress and Human Health","volume":"674","author":"Yang","year":"2009","journal-title":"Mutat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fncel.2018.00114","article-title":"Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4+T Cells in Neurodegenerative Diseases","volume":"12","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2478\/10004-1254-64-2013-2219","article-title":"Exposure to Urban Air Pollution and Bone Health in Clinically Healthy Six-Year-Old Children","volume":"64","author":"Francolira","year":"2013","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1189\/jlb.1008587","article-title":"Involvement of TLR2 and TLR4 in Inflammatory Immune Responses Induced by Fine and Coarse Ambient Air Particulate Matter","volume":"86","author":"Shoenfelt","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11657-017-0323-6","article-title":"Impact of Air Pollution on Vitamin D Deficiency and Bone Health in Adolescents","volume":"12","author":"Feizabad","year":"2017","journal-title":"Arch. Osteoporos."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/1\/27\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:44:40Z","timestamp":1760132680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/1\/27"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,30]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["toxics12010027"],"URL":"https:\/\/doi.org\/10.3390\/toxics12010027","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,30]]}}}