{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:15Z","timestamp":1789106835754,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Isotretinoin is widely used for the treatment of acne and has been associated with musculoskeletal and connective tissue disorder adverse events However, existing research remains limited in terms of large-scale systematic investigations of these adverse effects. This study utilized the FDA Adverse Event Reporting System the Canadian Vigilance Adverse Reaction Online Database (CVARD), and clinical data to comprehensively characterize the potential musculoskeletal and connective tissue toxicity of isotretinoin and to identify population-specific differences in adverse event patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Disproportionality analysis was conducted using the reporting odds ratio (ROR) method to identify potential safety signals. Subgroup analyses were performed according to sex, age, and dosage. Stratified ROR analyses were further conducted to evaluate reporting patterns associated with the concomitant use of oral contraceptives, tetracyclines, and prednisone. Time-to-onset characteristics were assessed using Weibull distribution analysis and cumulative temporal reporting distribution curves. Supplementary analyses were performed using external data from the CVARD database and clinical case series from the Affiliated Hospital of Qingdao University.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 30 positive safety signals were identified. The strongest signals were observed for epiphyses premature fusion (ROR = 216.92), SAPHO syndrome (ROR = 76.41), epiphyseal disorder (ROR = 51.42) and sacroiliitis (ROR = 45.36). Stratified analyses demonstrated male-predominant signals for SAPHO syndrome, epiphyses premature fusion, sacroiliitis, arthritis, and arthralgia (ROR ratios: 1.42\u20137.85). Adolescents exhibited significantly higher ROR ratios than adults for tendonitis, intervertebral disc degeneration, costochondritis, back pain, and arthralgia (ROR ratios: 2.30\u20137.41). Epiphyses premature fusion was predominantly reported in adolescents (n = 66, vs 2 adults), but the ROR for the adolescent versus adult comparison was not estimable owing to sparse data. All groups belonged to the early-failure pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sex- and age-stratified analyses identified several exploratory differences in reporting patterns. These exploratory findings provide hypothesis generating insights that warrant further validation in prospective clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1904582","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:29:02Z","timestamp":1789104542000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex- and age-specific musculoskeletal adverse events of isotretinoin: disproportionality analysis of the FAERS database combined with a clinical case series"],"prefix":"10.3389","volume":"17","author":[{"given":"Yidan","family":"Mu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xue","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Du","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Computer Science and Software Engineering, Southwest Petroleum University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.46497\/archrheumatol.2022.8645","article-title":"Evaluation of musculoskeletal adverse effects in patients on systemic isotretinoin treatment: a cross-sectional study","volume":"37","author":"Acar","year":"2022","journal-title":"Arch. 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