{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:07:17Z","timestamp":1793250437160,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health Welfare, Republic of Korea","award":["HR21C0885"],"award-info":[{"award-number":["HR21C0885"]}]},{"award":["HR21C0885"],"award-info":[{"award-number":["HR21C0885"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related disorders. However, there are concerns that PPI use may be associated with an increased risk of osteoporosis and fractures. This study aimed to investigate the association between PPI use and the risk of osteoporosis and fractures using national data. Methods: Two nested case\u2014control studies using Korean National Health Insurance Service-Health Screening Cohort (514,866 participants, 2002\u20132019). Study I: 68,719 osteoporosis patients matched 1:1 with 68,719 controls by age, sex, income, region. Study II: 72,456 fracture patients matched 1:1 with 72,456 controls, stratified by fracture site (distal radius [n = 25,882], hip [n = 7753], spine [n = 38,821]). PPI use defined as prescription 1-year preceding index date: current users (\u226430 days) and exposed group (31\u2013365 days). Associations were analyzed using propensity score overlap-weighted logistic regression. Results: For osteoporosis, current PPI use showed odds ratio (OR) = 37.4 (95% confidence interval [CI] 33.3\u201342.1, p &lt; 0.001); exposed group OR = 2.62 (95% CI 2.32\u20132.96, p &lt; 0.001). Duration-dependent relationship observed: &lt;30 days OR = 8.67, 30\u2013180 days OR = 29.9, \u2265180 days OR = 25.0. For fractures, current use associated with distal radius (OR = 37.4, 95% CI 28.8\u201348.7), hip (OR = 20.3, 95% CI 13.7\u201330.3), and spine (OR = 29.8, 95% CI 23.7\u201337.4). However, the exposed group showed no significant associations (distal radius OR = 1.24 p = 0.125; hip OR = 1.34 p = 0.174; spine OR = 1.26 p = 0.057). Conclusions: Current PPI use is strongly associated with increased odds of osteoporosis and fracture in the Asian population, with prominent duration\u2014response relationship. Past PPI exposure showed no significant fracture risk. Healthcare providers should carefully assess bone health risks and consider lowest effective PPI doses.<\/jats:p>","DOI":"10.3390\/jcm15103716","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:04:36Z","timestamp":1778601876000},"page":"3716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association Between the Use of Proton Pump Inhibitors and Osteoporosis\/Fracture: Nested Case\u2014Control Studies Using a National Health Screening Cohort"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4631-1504","authenticated-orcid":false,"given":"Hyun","family":"Youk","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea"},{"name":"MAIN Corp., Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4766-2329","authenticated-orcid":false,"given":"Jeong Mi","family":"Park","sequence":"additional","affiliation":[{"name":"Yonsei University Wonju Severance Christian Hospital, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Ji","family":"Kim","sequence":"additional","affiliation":[{"name":"MAIN Corp., Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yeong","family":"Park","sequence":"additional","affiliation":[{"name":"Yonsei University Wonju Severance Christian Hospital, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1655-9549","authenticated-orcid":false,"given":"Hyo Geun","family":"Choi","sequence":"additional","affiliation":[{"name":"Suseoseoulent Clinic, Seoul 06349, Republic of Korea"},{"name":"Mdanalytics, Seoul 06349, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2989-4952","authenticated-orcid":false,"given":"Jung Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea"},{"name":"Yonsei Institute of Sports Science and Exercise Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea"},{"name":"Biobytes Inc., Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s11657-022-01113-w","article-title":"Clinical features and burden of osteoporotic fractures among the elderly in the USA from 2016 to 2018","volume":"17","author":"Lou","year":"2022","journal-title":"Arch. 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