Effects of systemic administration of the retinoid Isotretinoin on bone tissue: A narrative literature review

Maria Júlia Bento Martins Parreira; Bruna Trazzi Pagani; Matheus Bento Medeiros Moscatel; Daniela Vieira Buchaim; Carlos Henrique Bertoni Reis; Beatriz Flávia de Moraes Trazzi; Acácio Fuziy; Rogerio Leone Buchaim; Maria Júlia Bento Martins Parreira; Bruna Trazzi Pagani; Matheus Bento Medeiros Moscatel; Daniela Vieira Buchaim; Carlos Henrique Bertoni Reis; Beatriz Flávia de Moraes Trazzi; Acácio Fuziy; Rogerio Leone Buchaim

doi:10.3934/bioeng.2024012

AIMS Bioengineering

2024, Volume 11, Issue 2: 212-240. doi: 10.3934/bioeng.2024012

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Review

Effects of systemic administration of the retinoid Isotretinoin on bone tissue: A narrative literature review

1.
Postgraduate Program in Applied Dental Sciences, Bauru School of Dentistry (FOB/USP), University of Sao Paulo, Bauru 17012-901, Brazil
2.
Dentistry School, University of Marilia (UNIMAR), Marilia 17525-902, Brazil
3.
Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil
4.
Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marilia 17525-902, Brazil
5.
Medical School, University Center of Adamantina (UNIFAI), Adamantina 17800-000, Brazil
6.
Marília Dental Specialization Center (CEO), Marilia 17516-000, Brazil
7.
Department of Biological Sciences, Bauru School of Dentistry (FOB/USP), University of Sao Paulo, Bauru 17012-901, Brazil

Received: 02 February 2024 Revised: 03 June 2024 Accepted: 26 June 2024 Published: 04 July 2024

Isotretinoin is an oral medication commonly utilized to treat severe acne. It belongs to the class of retinoids and is a synthetic form of vitamin A. Possible changes in bone tissue associated with the systemic administration of Isotretinoin for long periods and in high doses, such as hypercalcemia, osteopenia, diffuse hyperostosis, or even skeletal deformities, are reported in scientific studies. The objective of this literature review was to analyze the available scientific literature on the systemic administration of Isotretinoin and its effects on bone tissue. To this end, articles that demonstrate effects of Isotretinoin on bone metabolism, bone mineral density, bone formation, and resorption, in addition to possible changes generated in this tissue were considered valid for inclusion in this literature review. The search for articles that fit the premise of this work was carried out in the PubMed/MEDLINE database. In a preliminary search, 85 articles were obtained; after in-depth investigation and checking of the inclusion and exclusion criteria, 21 articles were selected, with 17 articles reporting the effect of systemic administration of Isotretinoin in humans and four articles analyzing the effect generated by this substance systemically administrated in animals, more specifically in rats. After analyzing the selected articles, it was possible to observe several reports on hyperostosis or even changes in the formation of bone structures in human patients. Concerning animals, the largest number of studies addressed the changes caused in the formation or development of bone structures by the systemic administration of Isotretinoin. From the current analyses, and given the wide use of Isotretinoin, it is necessary to know its viability and influence on tissues. Its clinical efficacy seems to overcome any of the skeletal side effects observed; however, more studies are necessary to properly evaluate and prove the effects generated on bone tissues as well as other structures.
- isotretinoin,
- bone repair,
- vitamin A,
- bone regeneration,
- retinoid,
- bone defects,
- bone
Citation: Maria Júlia Bento Martins Parreira, Bruna Trazzi Pagani, Matheus Bento Medeiros Moscatel, Daniela Vieira Buchaim, Carlos Henrique Bertoni Reis, Beatriz Flávia de Moraes Trazzi, Acácio Fuziy, Rogerio Leone Buchaim. Effects of systemic administration of the retinoid Isotretinoin on bone tissue: A narrative literature review[J]. AIMS Bioengineering, 2024, 11(2): 212-240. doi: 10.3934/bioeng.2024012

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Abstract

Isotretinoin is an oral medication commonly utilized to treat severe acne. It belongs to the class of retinoids and is a synthetic form of vitamin A. Possible changes in bone tissue associated with the systemic administration of Isotretinoin for long periods and in high doses, such as hypercalcemia, osteopenia, diffuse hyperostosis, or even skeletal deformities, are reported in scientific studies. The objective of this literature review was to analyze the available scientific literature on the systemic administration of Isotretinoin and its effects on bone tissue. To this end, articles that demonstrate effects of Isotretinoin on bone metabolism, bone mineral density, bone formation, and resorption, in addition to possible changes generated in this tissue were considered valid for inclusion in this literature review. The search for articles that fit the premise of this work was carried out in the PubMed/MEDLINE database. In a preliminary search, 85 articles were obtained; after in-depth investigation and checking of the inclusion and exclusion criteria, 21 articles were selected, with 17 articles reporting the effect of systemic administration of Isotretinoin in humans and four articles analyzing the effect generated by this substance systemically administrated in animals, more specifically in rats. After analyzing the selected articles, it was possible to observe several reports on hyperostosis or even changes in the formation of bone structures in human patients. Concerning animals, the largest number of studies addressed the changes caused in the formation or development of bone structures by the systemic administration of Isotretinoin. From the current analyses, and given the wide use of Isotretinoin, it is necessary to know its viability and influence on tissues. Its clinical efficacy seems to overcome any of the skeletal side effects observed; however, more studies are necessary to properly evaluate and prove the effects generated on bone tissues as well as other structures.

Conflicts of interest

Rogerio Leone Buchaim is an editorial board member for AIMS Bioengineering and was not involved in the editorial review or the decision to publish this article. The authors declare no conflict of interest.

Author contributions

Conceptualization, M.J.B.M.P. and R.L.B.; methodology, B.T.P., C.H.B.R., B.F.d.M.T. and M.B.M.M.; formal analysis, M.B.M.M.; investigation, B.T.P.; writing—original draft preparation, M.J.B.M.P.; writing—review and editing, R.L.B. and D.V.B.; visualization, A.F; supervision, R.L.B.; All authors have read and agreed to the published version of the manuscript.

References

[1]	Carazo A, Macáková K, Matoušová K, et al. (2021) Vitamin A update: Forms, sources, kinetics, detection, function, deficiency, therapeutic use and toxicity. Nutrients 13: 1703. https://doi.org/10.3390%2Fnu13051703
[2]	Coward KH (1927) The influence of light and heat on the formation of Vitamin A in plant tissues. J Biol Chem 72: 781-799. https://doi.org/10.1016/S0021-9258(18)84350-2
[3]	Schubert M, Germain P (2023) Retinoic acid and retinoid X receptors. Cells 12: 864. https://doi.org/10.3390/cells12060864
[4]	Berenguer M, Duester G (2022) Retinoic acid, RARs and early development. J Mol Endocrinol 69: T59-T67. https://doi.org/10.1530/jme-22-0041
[5]	Marill J, Idres N, Capron C, et al. (2003) Retinoic acid metabolism and mechanism of action: A review. Curr Drug Metab 4: 1-10. https://doi.org/10.2174/1389200033336900
[6]	Liang C, Qiao G, Liu Y, et al. (2021) Overview of all-trans-retinoic acid (ATRA) and its analogues: Structures, activities, and mechanisms in acute promyelocytic leukaemia. Eur J Med Chem 220: 113451. https://doi.org/10.1016/j.ejmech.2021.113451
[7]	Yonekura K, Takeda K, Kawakami N, et al. (2019) Therapeutic efficacy of etretinate on cutaneous-type adult T-cell leukemia-lymphoma. Acta Derm-Venereol 99: 774-776. https://doi.org/10.2340/00015555-3196
[8]	Hoover KB, Miller CG, Galante NC, et al. (2015) A double-blind, randomized, Phase III, multicenter study in 358 pediatric subjects receiving isotretinoin therapy demonstrates no effect on pediatric bone mineral density. Osteoporosis Int 26: 2441-2447. https://doi.org/10.1007/s00198-015-3158-2
[9]	Duvalyan A, Cha A, Goodarzian F, et al. (2020) Premature epiphyseal growth plate arrest after isotretinoin therapy for high-risk neuroblastoma: A case series and review of the literature. Pediatr Blood Cancer 67: e28236. https://doi.org/10.1002/pbc.28236
[10]	Knitzer RH, Needleman BW (1991) Musculoskeletal syndromes associated with acne. Semin Arthritis Rheu 20: 247-255. https://doi.org/10.1016/0049-0172(91)90020-z
[11]	Valentic JP, Elias AN, Weinstein GD (1983) Hypercalcemia associated with oral isotretinoin in the treatment of severe acne. JAMA 250: 1899-1900. https://doi.org/10.1001/jama.1983.03340140069034
[12]	Frankel TL, Seshadri MS, McDowall DB, et al. (1986) Hypervitaminosis A and calcium-regulating hormones in the rat. J Nutr 116: 578-587. https://doi.org/10.1093/jn/116.4.578
[13]	McLane J (2001) Analysis of common side effects of isotretinoin. J Am Acad Dermatol 45: S188-S194. https://doi.org/10.1067/mjd.2001.113719
[14]	Fleischer AB, Simpson JK, McMichael A, et al. (2003) Are there racial and sex differences in the use of oral isotretinoin for acne management in the United States?. J Am Acad Dermatol 49: 662-666. https://doi.org/10.1067/s0190-9622(03)01584-6
[15]	Goldsmith LA, Bolognia JL, Callen JP, et al. (2004) American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: Summary and recommendations. J Am Acad Dermatol 50: 900-906. https://doi.org/10.1016/j.jaad.2004.02.012
[16]	Campbell RM, DiGiovanna JJ (2006) Skin cancer chemoprevention with systemic retinoids: An adjunct in the management of selected high-risk patients. Dermatol Ther 19: 306-314. https://doi.org/10.1111/j.1529-8019.2006.00088.x
[17]	Cardoso-Demartini AA, Boguszewski CL, Boguszewski MCS (2023) Potential effects of oral isotretinoin on growth plate and height. Endocrines 4: 281-292. https://doi.org/10.3390/endocrines4020023
[18]	Kocijancic M (1995) 3-cis-retinoic acid and bone density. Int J Dermatol 34: 733-734. https://doi.org/10.1111/j.1365-4362.1995.tb04666.x
[19]	Melnik B, Glück S, Jungblut RM, et al. (1987) Retrospective radiographic study of skeletal changes after long-term etretinate therapy. Br J Dermatol 116: 207-212. https://doi.org/10.1111/j.1365-2133.1987.tb05813.x
[20]	McGuire J, Lawson JP (1987) Skeletal changes associated with chronic isotretinoin and etretinate administration. Dermatology 175: 169-181. https://doi.org/10.1159/000248881
[21]	King K, Jones DH, Daltrey DC, et al. (1982) A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population. Brit J Dermatol 107: 583-590. https://doi.org/10.1111/j.1365-2133.1982.tb00410.x
[22]	Costa CS, Bagatin E, Martimbianco ALC, et al. (2018) Oral isotretinoin for acne. Cochrane Db Syst Rev 11: CD009435. https://doi.org/10.1002/14651858.cd009435.pub2
[23]	Layton A (2009) The use of isotretinoin in acne. Dermatoendocrinol 1: 162-169. https://doi.org/10.4161%2Fderm.1.3.9364
[24]	Bagatin E, Costa CS, Rocha MAD, et al. (2020) Consensus on the use of oral isotretinoin in dermatology-Brazilian Society of Dermatology. An Bras Dermatol 95: 19-38. https://doi.org/10.1016/j.abd.2020.09.001
[25]	Pepe M, Napoli G, Carella MC, et al. (2023) A young patient presenting with dilated cardiomyopathy and renal infarction during treatment with isotretinoin: Mere coincidence or serious side effect of a drug commonly used in adolescence?. Diagnostics 13: 1543. https://doi.org/10.3390/diagnostics13091543
[26]	Cohen M, Rubinstein A, Li JK, et al. (1987) Thymic hypoplasia associated with isotretinoin embryopathy. Am J Dis Child 141: 263-266. https://doi.org/10.1001/archpedi.1987.04460030041020
[27]	Moerike S, Pantzar JT, De Sa D (2002) Temporal bone pathology in fetuses exposed to isotretinoin. Pediatr Devel Pathol 5: 405-409. https://doi.org/10.1007/s10024-001-0258-0
[28]	Rizzo R, Lammer EJ, Parano E, et al. (1991) Limb reduction defects in humans associated with prenatal isotretinoin exposure. Teratology 44: 599-604. https://doi.org/10.1002/tera.1420440602
[29]	Dai WS, LaBraico JM, Stern RS (1992) Epidemiology of isotretinoin exposure during pregnancy. J Am Acad Dermatol 26: 599-606. https://doi.org/10.1016/0190-9622(92)70088-w
[30]	Henry D, Dormuth C, Winquist B, et al. (2016) Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy. Can Med Assoc J 188: 723-730. https://doi.org/10.1503/cmaj.151243
[31]	Azoulay L, Blais L, Koren G, et al. (2008) Isotretinoin and the risk of depression in patients with acne vulgaris. J Clin Psychiatry 69: 526-532. https://doi.org/10.4088/jcp.v69n0403
[32]	Li C, Chen J, Wang W, et al. (2019) Use of isotretinoin and risk of depression in patients with acne: A systematic review and meta-analysis. BMJ Open 9: e021549. https://doi.org/10.1136/bmjopen-2018-021549
[33]	Abali R, Yuksel MA, Aktas C, et al. (2013) Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure. Reprod Biomed Online 27: 184-191. https://doi.org/10.1016/j.rbmo.2013.04.010
[34]	Şikar Aktürk A, Abalı R, Yüksel MA, et al. (2014) The effects of isotretinoin on the ovarian reserve of females with acne. Gynecol Endocrinol 30: 30-33. https://doi.org/10.3109/09513590.2013.860118
[35]	Aksoy H, Cinar L, Acmaz G, et al. (2015) The effect of isotretinoin on ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with acne. Gynecol Obstet Invest 79: 78-82. https://doi.org/10.1159/000371551
[36]	Öztürk S, Öztürk T, Ucak H, et al. (2015) Evaluation of ovarian reserve and function in female patients treated with oral isotretinoin for severe acne: An exploratory study. Cutan Ocul Toxicol 34: 21-24. https://doi.org/10.3109/15569527.2014.888079
[37]	Alhetheli G, Alhazmi S, Almutairi S, et al. (2022) The effects of isotretinoin on the menstrual cycle: A cross-sectional study. Clin Pract 12: 908-917. https://doi.org/10.3390%2Fclinpract12060095
[38]	Bergoli RD, Junior OLC, de Souza CECP, et al. (2011) Isotretinoin effect on alveolar repair after exodontia—A study in rats. Oral Maxillofac Surg 15: 85-92. https://doi.org/10.1007/s10006-010-0235-8
[39]	Cashin CH, Lewis EJ (1984) Evaluation of hypervitaminosis A in the rat by measurement of tibial bone breaking strain. J Pharmacol Methods 11: 91-95. https://doi.org/10.1016/0160-5402(84)90018-4
[40]	Hotchkiss CE, Latendresse J, Ferguson SA (2006) Oral treatment with retinoic acid decreases bone mass in rats. Comp Med 56: 502-511. https://www.ingentaconnect.com/contentone/aalas/cm/2006/00000056/00000006/art00007
[41]	De Oliveira HTR, Bergoli RD, Hirsch WDB, et al. (2013) Isotretinoin effect on the repair of bone defects—A study in rat calvaria. J Cranio Maxill Surg 41: 581-585. https://doi.org/10.1016/j.jcms.2012.11.030
[42]	Pennes DR, Martel W, Ellis CN (1985) Skeletal radiology retinoid-induced ossification of the posterior longitudinal ligament. Skeletal Radiol 14: 191-193. https://doi.org/10.1007/BF00355561
[43]	Ertugrul DT, Karadag AS, Tutal E, et al. (2011) Therapeutic hotline. Does isotretinoin have effect on vitamin D physiology and bone metabolism in acne patients?. Dermatol Ther 24: 291-295. https://doi.org/10.1111/j.1529-8019.2011.01406.x
[44]	Ellis CN, Madison KC, Pennes DR, et al. (1984) Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol 10: 1024-1029. https://doi.org/10.1016/s0190-9622(84)80329-1
[45]	Zhang R, Wang Y, Li R, et al. (2015) Transcriptional factors mediating retinoic acid signals in the control of energy metabolism. Int J Mol Sci 16: 14210-14244. https://doi.org/10.3390/ijms160614210
[46]	Kapała J, Lewandowska J, Placek W, et al. (2022) Adverse events in isotretinoin therapy: A single-arm meta-analysis. Int J Environ Res Public Health 19: 6463. https://doi.org/10.3390%2Fijerph19116463
[47]	Gencebay G, Aşkın Ö, Serdaroğlu S (2021) Evaluation of the changes in sebum, moisturization and elasticity in acne vulgaris patients receiving systemic isotretinoin treatment. Cutan Ocul Toxicol 40: 140-144. https://doi.org/10.1080/15569527.2021.1922434
[48]	Uslu M, Åžavk E, Karaman G, et al. (2012) Rosacea treatment with intermediate-dose isotretinoin: Follow-up with erythema and sebum measurements. Acta Derm-Venereol 92: 73-77. https://doi.org/10.2340/00015555-1204
[49]	Kmieć ML, Pajor A, Broniarczyk-Dyła G (2013) Evaluation of biophysical skin parameters and assessment of hair growth in patients with acne treated with isotretinoin. Adv Dermatology Allergol 6: 343-349. https://doi.org/10.5114/pdia.2013.39432
[50]	Minisola S, Pepe J, Piemonte S, et al. (2015) The diagnosis and management of hypercalcaemia. BMJ 350: h2723-h2723. https://doi.org/10.1136/bmj.h2723
[51]	Karaguzel G, Holick MF (2010) Diagnosis and treatment of osteopenia. Rev Endocr Metab Disord 11: 237-251. https://doi.org/10.1007/s11154-010-9154-0
[52]	Mader R, Verlaan JJ, Buskila D (2013) Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nat Rev Rheumatol 9: 741-750. https://doi.org/10.1038/nrrheum.2013.165
[53]	Kindmark A, Rollman O, Mallmin H, et al. (1998) Oral isotretinoin therapy in severe acne induces transient suppression of biochemical markers of bone turnover and calcium homeostasis. Acta Derm Venereol 78: 266-269. https://doi.org/10.1080/000155598441837
[54]	Leachman SA, Insogna KL, Katz L, et al. (1999) Bone densities in patients receiving isotretinoin for cystic acne. Arch Dermatol 135: 961-965. https://doi.org/10.1001/archderm.135.8.961
[55]	Karaosmanoğlu N, Mülkoğlu C (2020) Analysis of musculoskeletal side effects of oral Isotretinoin treatment: A cross-sectional study. BMC Musculoskelet Disord 21: 631. https://doi.org/10.1186/s12891-020-03656-w
[56]	DiGiovanna JJ (2001) Isotretinoin effects on bone. J Am Acad Dermatol 45: S176-S182. https://doi.org/10.1067/mjd.2001.113721
[57]	AlJasser R, AlAqeely R, AlZahrani A, et al. (2021) Antimicrobial effect of isotretinoin therapy on periodontal pathogens: A case-control study. Antibiotics 10: 1286. https://doi.org/10.3390/antibiotics10111286
[58]	Carey BM, Parkin GJS, Cunliffe WJ, et al. (1988) Skeletal toxicity with isotretinoin therapy: A clinico-radiological evaluation. Br J Dermatol 119: 609-614. https://doi.org/10.1111/j.1365–2133.1988.tb03471.x
[59]	Tangrea JA, Kilcoyne RF, Taylor PR, et al. (1992) Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin. Arch Dermatol 128: 921-925. https://doi.org/10.1001/archderm.1992.01680170053004
[60]	Archer CB, Elias PM, Lowe NJ, et al. (1989) Extensive spinal hyperostosis in a patient receiving isotretinoin—progression after 4 years of etretinate therapy. Clin Exp Dermatol 14: 319-321. https://doi.org/10.1111/j.1365-2230.1989.tb01993.x
[61]	Atalay A, Altaykan A, Ergin G, et al. (2004) Reversible sclerotic change of lumbar spine and femur due to long-term oral isotretinoin therapy. Rheumatol Int 24: 297-300. https://doi.org/10.1007/s00296-003-0391-3
[62]	Giannoulis CH, Papathanasiou K, Tantanasis TH, et al. (2005) Isotretinoin (Ro-Accutane) teratogenesis. A case report. Clin Exp Obstet Gyn 32: 78-80. https://www.imrpress.com/journal/CEOG/32/1/pii/2005023
[63]	Hoemberg S, Reinhard H (2017) Growth failure caused by premature epiphyseal closure in a child treated with isotretinoin for neuroblastoma. Klin Padiatr 229: 175-176. https://doi.org/10.1055/s-0043-103087
[64]	Luthi F, Eggel Y, Theumann N (2012) Premature epiphyseal closure in an adolescent treated by retinoids for acne: An unusual cause of anterior knee pain. Joint Bone Spine 79: 314-316. https://doi.org/10.1016/j.jbspin.2011.11.001
[65]	Marini JC, Hill S, Zasloff MA (1988) Dense metaphyseal bands and growth arrest associated with isotretinoin therapy. Arch Pediatr Adolesc Med 142: 316-318. https://doi.org/10.1001/archpedi.1988.02150030090029
[66]	Nishimura G, Mugishima H, Hirao J, et al. (1997) Generalized metaphyseal modification with cone-shaped epiphyses following long-term administration of 13-cis-retinoic acid. Eur J Pediatr 156: 432-435. https://doi.org/10.1007/s004310050631
[67]	Park WK, Choi HS, Chung CY, et al. (2020) Genu varum deformity due to premature epiphyseal closure after treatment with isotretinoin for neuroblastoma: A case report. J Orthop Surg (Hong Kong) 28: 2309499020924483. https://doi.org/10.1177/2309499020924483
[68]	Tekin NS, Ozdolap S, Sarikaya S, et al. (2008) Bone mineral density and bone turnover markers in patients receiving a single course of isotretinoin for nodulocystic acne. Int J Dermatol 47: 622-625. https://doi.org/10.1111/j.1365-4632.2008.03534.x
[69]	Torok L, Galuska L, Kasa M, et al. (1989) Bone-scintigraphic examinations in patients treated with retinoids: A prospective study. Brit J Dermatol 120: 31-36. https://doi.org/10.1111/j.1365-2133.1989.tb07762.x
[70]	Yang X, Wright JR, Yu W, et al. (2022) Parietal bone agenesis and athelia in retinoic acid embryopathy: An expansion of the phenotype. Birth Defects Res 114: 17-22. https://doi.org/10.1002/bdr2.1965
[71]	Melnik B, Kinner T, Plewig G (1988) Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris. Arch Dermatol Res 280: 97-102. https://doi.org/10.1007/bf00417712
[72]	Pratyusha K, Sree Pd, Reddy B (2016) Successful outcome of lamellar ichthyosis with oral retinoid therapy: A series of six cases. Indian J Paediatric Dermatology 17: 125-128. https://doi.org/10.4103/2319-7250.172464
[73]	Caytemel C, Demir FT, Uzuner EG, et al. (2020) Systemic isotretinoin treatment in a renal transplant patient developing sebaceous hyperplasia due to cyclosporine. North Clin Istanb 7: 628-630. https://doi.org/10.14744/nci.2019.00087
[74]	Digiovanna JJ, Langman CB, Tschen EH, et al. (2004) Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne. J Am Acad Dermatol 51: 709-717. https://doi.org/10.1016/j.jaad.2004.04.032
[75]	Draghici CC, Miulescu RG, Petca RC, et al. (2021) Teratogenic effect of isotretinoin in both fertile females and males (Review). Exp Ther Med 21: 1-5. https://doi.org/10.3892%2Fetm.2021.9966
[76]	Alshaalan ZM (2022) Knowledge on the use of isotretinoin and its side effects and awareness towards saudi FDA-pregnancy prevention program among the female acne patients: A northern saudi study. Medicina (Kaunas) 58: 1609. https://doi.org/10.3390/medicina58111609
[77]	Zhao S, Goodson NJ (2015) Diffuse idiopathic skeletal hyperostosis and isotretinoin in cystic acne. Case Reports : bcr2015209775. https://doi.org/10.1136%2Fbcr-2015-209775
[78]	Brzezinski P, Zonda GI, Hincu MA, et al. (2022) A multicenter cohort study evaluating the teratogenic effects of isotretinoin on neonates. Children 9: 1612. https://doi.org/10.3390/children9111612
[79]	Peinemann F, van Dalen EC, Kahangire DA, et al. (2015) Retinoic acid post consolidation therapy for high-risk neuroblastoma patients treated with autologous hematopoietic stem cell transplantation. Cochrane Db Syst Rev : CD010685. https://doi.org/10.1002/14651858.cd010685.pub3
[80]	Bayeva N, Coll E, Piskareva O (2021) Differentiating neuroblastoma: A systematic review of the retinoic acid, its derivatives, and synergistic interactions. J Pers Med 11: 211. https://doi.org/10.3390/jpm11030211
[81]	Rhinn M, Dollé P (2012) Retinoic acid signalling during development. Development 139: 843-858. https://doi.org/10.1242/dev.065938
[82]	Masetti R, Biagi C, Zama D, et al. (2012) Retinoids in pediatric onco-hematology: The model of acute promyelocytic leukemia and neuroblastoma. Adv Ther 29: 747-762. https://doi.org/10.1007/s12325-012-0047-3
[83]	Steineck A, MacKenzie JD, Twist CJ (2016) Premature physeal closure following 13-cis-retinoic acid and prolonged fenretinide administration in neuroblastoma. Pediatr Blood Cancer 63: 2050-2053. https://doi.org/10.1002/pbc.26124
[84]	Hobbie WL, Moab SM, Carlson CA, et al. (2011) Prevalence of advanced bone age in a cohort of patients who received cis-retinoic acid for high-risk neuroblastoma. Pediatr Blood Cancer 56: 474-476. https://doi.org/10.1002/pbc.22839
[85]	Maleki A, Qoreishi M, Bisadi A, et al. (2023) The efficacy of hemiepiphysiodesis for idiopathic knee coronal angular deformity by reconstruction plate and screw: A pilot study. Health Sci Rep 6: e1302. https://doi.org/10.1002/hsr2.1302
[86]	Matsuoka M, Onodera T, Majima T, et al. (2019) Correction osteotomy for bilateral varus knee deformity caused by premature epiphyseal closure induced by hypervitaminosis A: A case report. BMC Musculoskel Dis 20: 287. https://doi.org/10.1186%2Fs12891-019-2665-2
[87]	Milstone LM, McGuire J, Ablow RC (1982) Premature epiphyseal closure in a child receiving oral 13-cis-retinoic acid. J Am Acad Dermatol 7: 663-666. https://doi.org/10.1016/s0190-9622(82)70148-3
[88]	Novick NL, Lawson W, Schwartz IS (1984) Bilateral nasal bone osteophytosis associated with short-term oral isotretinoin therapy for cystic acne vulgaris. Am J Med 77: 736-739. https://doi.org/10.1016/0002-9343(84)90376-0
[89]	Koh KN, Jeon JY, Park SS, et al. (2021) Physeal abnormalities in children with high-risk neuroblastoma intensively treated with/without 13-cis-retinoic acid. J Pediatr Orthoped 41: e841-e848. https://doi.org/10.1097/bpo.0000000000001946
[90]	Contreras-Olea O, Goecke-Hochberger C, Rumié-Carmi HK, et al. (2019) Fibrodisplasia osificante progresiva plus por una variante patogénica del gen ACVR1: Caso clínico. Rev Med Chil 147: 384-389. http://dx.doi.org/10.4067/S0034-98872019000300384
[91]	Standeven AM, Davies PJA, Chandraratna RAS, et al. (1996) Retinoid-induced epiphyseal plate closure in guinea pigs. Fundamental Applied Toxicol 34: 91-98. https://doi.org/10.1006/faat.1996.0179

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