{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:40:41Z","timestamp":1791330041710,"version":"4.3.1"},"reference-count":28,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jom-2021-0108_abs_001\">\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients. Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia. Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U.S. Food and Drug Administration (FDA) has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne. It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2021-0108_abs_002\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2021-0108_abs_003\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two databases were utilized for the literature review and were conducted at different time periods. Our literature review was conducted between December 2020 and June 2021, utilizing PubMed with the following search terms: \u201cisotretinoin\u201d and \u201cisotretinoin and premature epiphyseal closure.\u201d In April 2021, we searched the FDA\u2019s \u201cDrug Data and Adverse Event Report System\u201d utilizing the terms \u201cisotretinoin\u201d and \u201cepiphysis premature fusion.\u201d We included in our query reports of patients worldwide under 18\u00a0years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. Studies published in English between 1980 and 2020 were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2021-0108_abs_004\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin. The FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18\u00a0years of age. Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0.5\u00a0mg\/kg\/day for a few months to 3.5\u00a0mg\/kg\/day for years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2021-0108_abs_005\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment, which are much lower compared to the high doses utilized for neuroblastoma. Based on this study, isotretinoin appears to impact the growth plates of proximal tibia and distal femur. A cause-and-effect relationship between isotretinoin and premature epiphyseal closure cannot be concluded.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jom-2021-0108","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T21:59:03Z","timestamp":1633989543000},"page":"45-53","source":"Crossref","is-referenced-by-count":17,"title":["Analysis of the effects of isotretinoin on the premature epiphyseal closure in pediatric populations: a literature review"],"prefix":"10.1515","volume":"122","author":[{"given":"Sama","family":"Alazawi","sequence":"first","affiliation":[{"name":"Touro University College of Osteopathic Medicine , Vallejo , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"Hendriksz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Touro University College of Osteopathic Medicine , Vallejo , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"2023040101180493312_j_jom-2021-0108_ref_001","unstructured":"Leyden, JJ, Del Rosso, JQ, Baum, EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol 2014;7(2 Suppl):S3\u201321."},{"key":"2023040101180493312_j_jom-2021-0108_ref_002","doi-asserted-by":"crossref","unstructured":"Zaenglein, AL, Pathy, AL, Schlosser, BJ, Alikhan, A, Baldwin, HE, Berson, DS, et al.. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945\u201373.e33. https:\/\/doi.org\/10.1016\/j.jaad.2015.12.037.","DOI":"10.1016\/j.jaad.2015.12.037"},{"key":"2023040101180493312_j_jom-2021-0108_ref_003","doi-asserted-by":"crossref","unstructured":"Matthay, KK, Villablanca, JG, Seeger, RC, Stram, DO, Harris, RE, Ramsay, NK, et al.. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children\u2019s Cancer Group. N Engl J Med 1999;341:1165\u201373. https:\/\/doi.org\/10.1056\/NEJM199910143411601.","DOI":"10.1056\/NEJM199910143411601"},{"key":"2023040101180493312_j_jom-2021-0108_ref_004","doi-asserted-by":"crossref","unstructured":"Otley, CC, Stasko, T, Tope, WD, Lebwohl, M. Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects. Dermatol Surg 2006;32:562\u20138. https:\/\/doi.org\/10.1111\/j.1524-4725.2006.32115.x.","DOI":"10.1111\/j.1524-4725.2006.32115.x"},{"key":"2023040101180493312_j_jom-2021-0108_ref_005","doi-asserted-by":"crossref","unstructured":"Duvic, M, Apisarnthanarax, N, Cohen, DS, Smith, TL, Ha, CS, Kurzrock, R. Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol 2003;49:35\u201349. https:\/\/doi.org\/10.1067\/mjd.2003.449.","DOI":"10.1067\/mjd.2003.449"},{"key":"2023040101180493312_j_jom-2021-0108_ref_006","unstructured":"U.S Food & Drug Administration. 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Premature epiphyseal closure secondary to single-course vitamin A therapy. Aust N Z J Surg 1999;69:825\u20137.","DOI":"10.1046\/j.1440-1622.1999.01706.x"},{"key":"2023040101180493312_j_jom-2021-0108_ref_010","doi-asserted-by":"crossref","unstructured":"Brecher, AR, Orlow, SJ. Oral retinoid therapy for dermatologic conditions in children and adolescents. J Am Acad Dermatol 2003;49:171\u201386. https:\/\/doi.org\/10.1067\/s0190-9622(03)01564-0.","DOI":"10.1067\/S0190-9622(03)01564-0"},{"key":"2023040101180493312_j_jom-2021-0108_ref_011","doi-asserted-by":"crossref","unstructured":"Lammer, EJ, Chen, DT, Hoar, RM, Agnish, ND, Benke, PJ, Braun, JT, et al.. Retinoic acid embryopathy. N Engl J Med 1985;313:837\u201341. https:\/\/doi.org\/10.1056\/NEJM198510033131401.","DOI":"10.1056\/NEJM198510033131401"},{"key":"2023040101180493312_j_jom-2021-0108_ref_012","doi-asserted-by":"crossref","unstructured":"Tkachenko, E, Singer, S, Sharma, P, Barbieri, J, Mostaghimi, A. US food and drug administration reports of pregnancy and pregnancy-related adverse events associated with isotretinoin. JAMA Dermatol 2019;155:1175\u20139. https:\/\/doi.org\/10.1001\/jamadermatol.2019.1388.","DOI":"10.1001\/jamadermatol.2019.1388"},{"key":"2023040101180493312_j_jom-2021-0108_ref_013","doi-asserted-by":"crossref","unstructured":"Lee, YH, Scharnitz, TP, Muscat, J, Chen, A, Gupta-Elera, G, Kirby, JS. Laboratory monitoring during isotretinoin therapy for acne: a systematic review and meta-analysis. JAMA Dermatol 2016;152:35\u201344. https:\/\/doi.org\/10.1001\/jamadermatol.2015.3091.","DOI":"10.1001\/jamadermatol.2015.3091"},{"key":"2023040101180493312_j_jom-2021-0108_ref_014","doi-asserted-by":"crossref","unstructured":"Kvist, O, Luiza Dallora, A, Nilsson, O, Anderberg, P, Sanmartin Berglund, J, Flodmark, CE, et al.. A cross-sectional magnetic resonance imaging study of factors influencing growth plate closure in adolescents and young adults. 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