{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T11:46:27Z","timestamp":1792323987958,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T00:00:00Z","timestamp":1645228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000139","name":"Environmental Protection Agency","doi-asserted-by":"publisher","award":["No. RD83587101"],"award-info":[{"award-number":["No. RD83587101"]}],"id":[{"id":"10.13039\/100000139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MD012769"],"award-info":[{"award-number":["R01MD012769"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Bone health is a major concern for aging populations globally. Osteoporosis and bone mineral density are associated with air pollution, but less is known about the impacts of air pollution on osteoporotic fracture. We aimed to assess the associations between long-term air pollution exposure and risk of osteoporotic fracture in seven large Korean cities. We used Cox proportional hazard models to estimate hazard rations (HRs) of time-varying moving window of past exposures of particulate matter (PM10), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3) for osteoporotic fracture in Korean adults (age \u2265 50 years) in the National Health Insurance Service-National Sample Cohort data, followed 2002 to 2015. HRs were calculated for an interquartile range (IQR) increase. Comorbidity and prescription associated with osteoporosis, age, sex, body mass index, health behaviors, and income were adjusted in the models. Effect modification by age, sex, exercise, and income was examined. We assessed 56,467 participants over 535,481 person-years of follow up. Linear and positive exposure-response associations were found for SO2, while PM10 and NO2 showed nonlinear associations. SO2 was associated with osteoporosis-related fracture with marginal significance (HR for an IQR [2 ppb] increase = 1.04, 95% CI: 1.00, 1.09). The SO2 HR estimates were robust in analyses applying various moving windows of exposure (from one to three years of past exposure) and two-pollutant models. The central HR estimate of O3 implied positive associations but was not significant (HR for 0.007 ppm increase = 1.01, 95% CI: 0.97, 1.06). PM10, CO, and NO2 did not show associations. Vulnerable groups by sex, age, exercise, and income varied across air pollutants and there was no evidence of effect modifications. Long-term exposure to SO2, but not PM10, CO, NO2 and O3, was associated with increased osteoporotic fracture risks in Korean adults.<\/jats:p>","DOI":"10.3390\/ijerph19042404","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:18:05Z","timestamp":1645431485000},"page":"2404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Associations between Long-Term Air Pollution Exposure and Risk of Osteoporosis-Related Fracture in a Nationwide Cohort Study in South Korea"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0786-5002","authenticated-orcid":false,"given":"Seulkee","family":"Heo","sequence":"first","affiliation":[{"name":"School of the Environment, Yale University, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-3428","authenticated-orcid":false,"given":"Honghyok","family":"Kim","sequence":"additional","affiliation":[{"name":"School of the Environment, Yale University, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-2080","authenticated-orcid":false,"given":"Sera","family":"Kim","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Precision Public Health, Department of Public Health Sciences, Graduate School of Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6270-5020","authenticated-orcid":false,"given":"Seung-Ah","family":"Choe","sequence":"additional","affiliation":[{"name":"College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-6250","authenticated-orcid":false,"given":"Garam","family":"Byun","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Precision Public Health, Department of Public Health Sciences, Graduate School of Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Precision Public Health, Department of Public Health Sciences, Graduate School of Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-1359","authenticated-orcid":false,"given":"Michelle L.","family":"Bell","sequence":"additional","affiliation":[{"name":"School of the Environment, Yale University, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110888","DOI":"10.1016\/j.envres.2021.110888","article-title":"Long-Term Exposure to Fine Particulate Matter and Osteoporotic Fracture: A Case\u2013Control Study in Taiwan","volume":"196","author":"Chiu","year":"2021","journal-title":"Environ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111547","DOI":"10.1016\/j.envres.2021.111547","article-title":"Association of Green Space with Bone Mineral Density Change and Incident Fracture in Elderly Hong Kong Chinese: Mr. OS and Ms. OS Study","volume":"201","author":"Lin","year":"2021","journal-title":"Environ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3961\/jpmph.18.114","article-title":"Environmental Air Pollution and the Risk of Osteoporosis and Bone Fractures","volume":"51","author":"Nguyen","year":"2018","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.afos.2018.03.003","article-title":"An Updated Hip Fracture Projection in Asia: The Asian Federation of Osteoporosis Societies Study","volume":"4","author":"Cheung","year":"2018","journal-title":"Osteoporos. Sarcopenia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"309","DOI":"10.18043\/ncm.79.5.309","article-title":"The Unexpected Health Effects of Air Pollution","volume":"79","author":"Peden","year":"2018","journal-title":"North Carol. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.chest.2018.10.041","article-title":"Air Pollution and Noncommunicable Diseases: A Review by the Forum of International Respiratory Societies\u2019 Environmental Committee, Part 2: Air Pollution and Organ Systems","volume":"155","author":"Schraufnagel","year":"2019","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109465","DOI":"10.1016\/j.envres.2020.109465","article-title":"Molecular and Cellular Mechanisms Linking Air Pollution and Bone Damage","volume":"185","author":"Prada","year":"2020","journal-title":"Environ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lin, Y.-H., Wang, C.-F., Chiu, H., Lai, B.-C., Tu, H.-P., Wu, P.-Y., Huang, J.-C., and Chen, S.-C. (2020). Air Pollutants Interaction and Gender Difference on Bone Mineral Density T-Score in Taiwanese Adults. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17249165"},{"key":"ref_9","first-page":"e2020023","article-title":"Effects of Sulfur Dioxide, Ozone, and Ambient Air Pollution on Bone Metabolism Related Biochemical Parameters in a Rat Model","volume":"35","author":"Kheirouri","year":"2020","journal-title":"Sulfur Dioxide"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/08958370304476","article-title":"Oxidative Damage of Sulfur Dioxide on Various Organs of Mice: Sulfur Dioxide Is a Systemic Oxidative Damage Agent","volume":"15","author":"Meng","year":"2003","journal-title":"Inhal. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1210\/jc.2007-2663","article-title":"Urban Tropospheric Ozone Increases the Prevalence of Vitamin D Deficiency among Belgian Postmenopausal Women with Outdoor Activities during Summer","volume":"93","author":"Manicourt","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","first-page":"84","article-title":"Air Pollution and Genetic Influences on Bone Mineral Density and Osteoporosis","volume":"17","author":"Cevei","year":"2010","journal-title":"Analele Universit\u0103\u021bii din Oradea, Fascicula Biologie"},{"key":"ref_13","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_14","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_15","doi-asserted-by":"crossref","first-page":"109264","DOI":"10.1016\/j.envres.2020.109264","article-title":"Long-Term Exposure to Air Pollution Might Increase Prevalence of Osteoporosis in Chinese Rural Population","volume":"183","author":"Qiao","year":"2020","journal-title":"Environ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1007\/s00198-009-1130-8","article-title":"Outdoor Air Pollution, Bone Density and Self-Reported Forearm Fracture: The Oslo Health Study","volume":"21","author":"Alver","year":"2010","journal-title":"Osteoporos. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1007\/s00198-018-4605-7","article-title":"Short-Term Association between Outdoor Air Pollution and Osteoporotic Hip Fracture","volume":"29","author":"Mazzucchelli","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s00774-020-01117-x","article-title":"Association of Air Pollution with Osteoporotic Fracture Risk among Women over 50 Years of Age","volume":"38","author":"Sung","year":"2020","journal-title":"J. Bone Min. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kim, H.Y., Jang, E.J., Park, B., Kim, T.-Y., Shin, S.-A., Ha, Y.-C., and Jang, S. (2016). Development of a Korean Fracture Risk Score (KFRS) for Predicting Osteoporotic Fracture Risk: Analysis of Data from the Korean National Health Insurance Service. PLoS ONE, 11.","DOI":"10.1530\/boneabs.5.P347"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3803\/EnM.2013.28.2.90","article-title":"Epidemiology of Osteoporosis and Osteoporotic Fractures in South Korea","volume":"28","author":"Lee","year":"2013","journal-title":"Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e311","DOI":"10.1016\/S2542-5196(17)30143-2","article-title":"Air Pollution: A Largely Neglected Risk Factor for Osteoporosis","volume":"1","author":"Nguyen","year":"2017","journal-title":"Lancet Planet. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.14373\/JKDA.2013.19.1.046","article-title":"Calcium Intakes in Korean and American Populations (in Korean)","volume":"19","author":"Yu","year":"2013","journal-title":"J. Korean Diet. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"89","DOI":"10.21032\/jhis.2017.42.1.89","article-title":"Data Issues and Suggestions in the National Health Insurance Service-National Sample Cohort for Assessing the Long-term Health Effects of Air Pollution Focusing on Mortality","volume":"42","author":"Kim","year":"2017","journal-title":"J. Health Inform. Stat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.3346\/jkms.2018.33.e48","article-title":"Incidence and Seasonal Variation of Distal Radius Fractures in Korea: A Population-Based Study","volume":"33","author":"Jo","year":"2018","journal-title":"J. Korean Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3346\/jkms.2011.26.8.1087","article-title":"Incidence and Mortality Following Hip Fracture in Korea","volume":"26","author":"Yoon","year":"2011","journal-title":"J. Korean Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105","DOI":"10.11005\/jbm.2019.26.2.105","article-title":"Incidence of Osteoporotic Refractures Following Proximal Humerus Fractures in Adults Aged 50 Years and Older in Korea","volume":"26","author":"Jung","year":"2019","journal-title":"J. Bone Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.spinee.2019.09.025","article-title":"Incidence and Mortality of Subsequent Vertebral Fractures: Analysis of Claims Data of the Korea National Health Insurance Service from 2007 to 2016","volume":"20","author":"Park","year":"2020","journal-title":"Spine J."},{"key":"ref_28","unstructured":"(2021, September 09). The National Ambient air Monitoring Information System (NAMIS). Available online: https:\/\/airkorea.or.kr\/web."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jocd.2013.03.014","article-title":"Fracture Risk Prediction Using Phalangeal Bone Mineral Density or FRAX\u00ae?\u2014A Danish Cohort Study on Men and Women","volume":"17","author":"Rubin","year":"2014","journal-title":"J. Clin. Densitom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.bone.2011.11.006","article-title":"Probability of Fractures Predicted by FRAX\u00ae and Observed Incidence in the Spanish ECOSAP Study Cohort","volume":"50","author":"Marin","year":"2012","journal-title":"Bone"},{"key":"ref_31","first-page":"188","article-title":"Charlson Comorbidity Index: ICD-9 Update and ICD-10 Translation","volume":"12","author":"Glasheen","year":"2019","journal-title":"Am. Health Drug Benefits"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s11154-010-9153-1","article-title":"Cellular Mechanisms of Bone Remodeling","volume":"11","author":"Eriksen","year":"2010","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1038\/s41416-018-0302-8","article-title":"Assessment of Proportional Hazard Assumption in Aggregate Data: A Systematic Review on Statistical Methodology in Clinical Trials Using Time-to-Event Endpoint","volume":"119","author":"Rulli","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1007\/s00198-021-05961-z","article-title":"Association between Outdoor Particulate Air Pollution and the Risk of Osteoporosis: A Systematic Review and Meta-Analysis","volume":"32","author":"Liu","year":"2021","journal-title":"Osteoporos. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jes.2015.08.028","article-title":"An Overview of Emissions of SO2 and NOx and the Long-Range Transport of Oxidized Sulfur and Nitrogen Pollutants in East Asia","volume":"44","author":"Qu","year":"2016","journal-title":"J. Environ. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.2147\/RMHP.S316429","article-title":"Particulate Air Pollution and Osteoporosis: A Systematic Review","volume":"14","author":"Pang","year":"2021","journal-title":"Risk Manag. Healthc. Policy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110290","DOI":"10.1016\/j.envres.2020.110290","article-title":"Effects of Long-Term Exposure to Air Pollution on All-Cause Mortality and Cause-Specific Mortality in Seven Major Cities of South Korea: Korean National Health and Nutritional Examination Surveys with Mortality Follow-Up","volume":"192","author":"Kim","year":"2021","journal-title":"Environ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104954","DOI":"10.1016\/j.envint.2019.104954","article-title":"Effect of Air Pollutant Emission Reduction Policies on Hospital Visits for Asthma in Seoul, Korea; Quasi-Experimental Study","volume":"132","author":"Kim","year":"2019","journal-title":"Environ. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.envint.2018.09.004","article-title":"Spatial Variation in Lag Structure in the Short-Term Effects of Air Pollution on Mortality in Seven Major South Korean Cities, 2006\u20132013","volume":"125","author":"Kim","year":"2019","journal-title":"Environ. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105500","DOI":"10.1016\/j.envint.2020.105500","article-title":"PM2.5 and NO2 Exposure Errors Using Proxy Measures, Including Derived Personal Exposure from Outdoor Sources: A Systematic Review and Meta-Analysis","volume":"137","author":"Evangelopoulos","year":"2020","journal-title":"Environ. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1097\/JOM.0000000000002041","article-title":"Exposure to Air Pollution and Risk of Hip Fracture: A Population-Based Cohort Study With a 6-Year Follow-Up in South Korea","volume":"62","author":"Oh","year":"2020","journal-title":"J. Occup. Environ. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3928\/0147-7447-20050201-17","article-title":"The Effects of Weather and Seasonality of Hip Fracture Incidence in Older Adults","volume":"28","author":"Mirchandani","year":"2005","journal-title":"Orthopedics"},{"key":"ref_44","first-page":"299","article-title":"Effect of Seasonality, Weather and Holidays on the Incidence of Proximal Hip Fracture","volume":"16","author":"Koren","year":"2014","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s00198-007-0364-6","article-title":"Effect of Seasonality and Weather on Fracture Risk in Individuals 65 Years and Older","volume":"18","author":"Orav","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4332\/KJHPA.2012.22.1.049","article-title":"Determinants of Health Screening and Its Effects on Health Behaviors","volume":"22","author":"Yeo","year":"2012","journal-title":"Health Policy Manag."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/4\/2404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:23:02Z","timestamp":1760134982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/4\/2404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,19]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijerph19042404"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19042404","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,19]]}}}