{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:58:59Z","timestamp":1784303939997,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Dimethyl fumarate (DMF) is currently recommended as a first\u2010line therapy for multiple sclerosis (MS). Investigating its adverse events (AEs) holds significant clinical importance. This study aimed to explore the association between DMF and fracture\u2010related AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024) were analyzed using disproportionality analysis. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM) were employed to identify and characterize AEs. Age\u2010 and gender\u2010specific subgroup analyses were conducted to evaluate AE patterns. Additionally, Weibull distribution analysis was performed to assess the temporal relationship of AE onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, spinal fusion fracture (ROR\u2009=\u200913.13, 95% CI: 1.73\u201399.86) and coccyx fracture (ROR\u2009=\u20093.05, 95% CI: 1.92\u20134.86) exhibited the strongest signals. Gender and age heterogeneity were observed in DMF\u2010associated fracture risks. Female patients showed the highest signals for spinal fusion bone fracture (ROR\u2009=\u200913.13) and coccyx fracture (ROR\u2009=\u20092.80), while males predominantly exhibited patella (ROR\u2009=\u20094.94) and scapula fractures (ROR\u2009=\u20093.68). Age stratification revealed elevated risks of forearm fracture (ROR\u2009=\u200910.29, 95% CI: 4.24\u201324.96) and ankle fracture (ROR\u2009=\u20095.63, 95% CI: 4.32\u20137.35) in elderly patients, whereas younger populations displayed diverse multi\u2010site fractures. Time\u2010to\u2010onset (TTO) analysis indicated that 63.62% of fractures occurred within the first 2\u2009years of the treatment cycle, with a median onset time of 506\u2009days. Weibull distribution modeling indicated that DMF's failure pattern aligned with an early failure\u2010type curve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DMF use is associated with an increased risk of fracture\u2010related AEs, with demographic variations in susceptibility. This study provides critical insights into the safety profile of DMF in MS management, underscoring the need for vigilance in high\u2010risk populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70612","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T07:11:41Z","timestamp":1757661101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fracture Risk Associated With Dimethyl Fumarate Treatment in Multiple Sclerosis Patients: Population Heterogeneity and Temporal Patterns"],"prefix":"10.1111","volume":"31","author":[{"given":"Dongdong","family":"He","sequence":"first","affiliation":[{"name":"Department of Orthopedics Second Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingkai","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Second Hospital of Shanxi Medical University  Taiyuan China"},{"name":"Shanxi Provincial Key Laboratory of Bone and Soft Tissue Injury Repair  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peirui","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Shanxi Medical University  Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujia","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Stomatology Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feida","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Second Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-6443","authenticated-orcid":false,"given":"Chuan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Second Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000622"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000037297"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737167.2015.1067141"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt-2021-0058"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/20552173211010832"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211037909"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-23834-1"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100315"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200326030-00002"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2021.1948529"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050466"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200225060-00001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1742"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.668"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/17448069221124920"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009404"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12826"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13548"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2018.11.017"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-018-8481-2"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518791132"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00162-3"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.965258"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-009-0023-2"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28550"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16142307"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.5402\/2011\/238607"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.10.039"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169465"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-022-03208-3"}],"container-title":["CNS Neuroscience &amp; 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