Isotretinoin: Possible Interference in Postextraction Healing Isotretinoina: Possível Interferência na Cicatrização Pós-Exodontia
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Published:
Oct 21, 2020
Keywords:
Anti-acne., 13-cis-Retinoic Acid., Isotretinoin., Acne vulgaris., Drug-related side effects., Wound Healing., Maxillofacial Surgery.
Main Article Content
Abstract
Pharmacovigilance is defined as “the science and activities related to identification, evaluation, understanding and prevention of adverse effects or problems related to the use of drugs”. All drugs have both the potential to cause harm and benefit. 13-cis-Retinoic acid or isotretinoin is a reference anti-acne retinoid in the dermatological diseases treatment not responsive to conventional therapies, such as severe cystic acne. The drug-related side effects described in the medicine package insert imply changes in various human body systems. Those related to bone tissue, such as ligaments and tendons calcification, bone density reduction, epiphyseal closure and hypercalcemia, have great relevance for dentistry, raising the hypothesis of a possible interference in alveoli wound healing after extraction. This article aimed to conduct a literature review in gathering information about the possibility of isotretinoin interference in maxillofacial surgeries. In despite of the scarcity of conclusive scientific data about the influence of isotretinoin on human alveolar wound healing, recent studies on retinoid signaling pathways open new research perspectives for the isotretinoin interference on alveolar bone tissue. This possibility reinforces the importance of an isotretinoin drug-related side effects update, as well as a patients’ careful anamnesis with historical severe acne, in order to avoid complications.
Article Details
How to Cite
Luana Clementino Cordeiro, Marcelly Marques Bittencourt, Wilton da Silveira Chaves Júnior, & Christina Gaspar Villela. (2020). Isotretinoin: Possible Interference in Postextraction Healing. Naval Dental Jounal, 47(2), 58-67. https://doi.org/10.29327/25149.47.2-7
Section
Literature Reviews
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
1. Xiao JH, Durand B, Chambon P, Voorhees JJ. Endogenous Retinoic Acid Receptor (RAR)-Retinoid X Receptor (RXR) Heterodimers Are the Major Functional Forms Regulating Retinoid-responsive Elements in Adult Human Keratinocytes. Binding of ligands to RAR only is sufficient for RAR•RXR heterodimers to confer ligand-dependent activation of hRARβ2/RARE (DR5). J Biol Chem. 1995;270(7):3001-3011.
2. Chandraratna RAS. Tazarotene, first of a new generation of receptor selective retinoids. Br J Dermatol. 1996;135 Suppl 49:18-25.
3. Hoyos B, Imam A, Chua R, Swenson C, Tong GX, Levi E, et al. The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptor. J Exp Med. 2000;192:835-845.
4. Aggarwal S, Kim SW, Cheon K, Tabassam FH, Yoon JH, Koo S. Nonclassical action of retinoic acid on the activation of the cAMP response element binding protein in normal human bronchial epithelial cells. Mol Biol Cell. 2006;17:566-575.
5. Sewell MJ, Burkhart CN, Morrell DS. Farmacologia dermatológica. In: Brunton LL, Hilal-Dandan R, Knollman B, editors. As bases farmacológicas da terapêutica de Goodman e Gilman. Porto Alegre: AMGH; 2019. p. 1563-1594.
6. Khalil S, Bardawil T, Stephan C, Darwiche N, Abbas O, Kibbi AG, et al. Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects. J Dermatolog Treat. 2017;28(8):684-696.
7. Isotretinoina. [Bula]. Rio de Janeiro: Produtos Roche Químicos e Farmacêuticos S.A.; 2018.
8. Ellis CN; Krach KJ. Uses and complications of isotretinoin therapy. J Am Acad Dermatol. 2001;45(5):S150-157.
9. David J. Margolis, MD; Maurice Attie, MD; James J. Leyden, MD. Effects of isotretinoin on bone mineralization during routine therapy with isotretinoin for acne vulgaris. Dermatol. 1996;132(7):769-774.
10. Bergoli RD. Efeito da isotretinoina no reparo alveolar após exodontia - Estudo em ratos. [Dissertação de Mestrado]. Porto Alegre: Pontifícia Universidade Católica do Rio Grande do Sul; 2009.
11. Oliveira HTR. Efeito da isotretinoina no reparo de defeitos ósseos em calota craniana – estudo em ratos. [Tese de doutorado]. Porto Alegre: Pontifícia Universidade Católica do Rio Grande do Sul; 2009.
12. Cayman Chemical. [Internet]. Vitamin A (20241); Isotretinoin (21648); All-trans retinoic acid (11017); 9-cis-retinoic acid (14587); All-trans-4-hydroxy retinoic acid (21378). [acesso em 2020 Jun 28]. Disponível em: https://www.caymanchem.com/HMRP#:~:text=For%20every%20step%20of%20your,the%20discretion%20of%20Cayman%20Chemical.
13. Szanto A, Narkar V, Shen Q, Uray IP, Davies PJA, Nagy L. Review. Retinoid X Receptors: X-Ploring Their (Patho) Physiological Functions. Cell Death Differ. 2004;11 Suppl 2:S126-143.
14. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992;68(2):397-406.
15. Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, et al. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature. 1992;355:359-361.
16. Layton A. Review. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162-9.
17. Lal L, Li Y, Smith J, Sassano A; Uddin S, Parmar S, et al. Activation of the p70 S6 Kinase by All-Trans-Retinoic Acid in Acute Promyelocytic Leukemia Cells. Blood. 2005;105(4):1669-1677.
18. Zhao Q, Tao J, Zhu Q, Jia PM, Dou AX, Li X, et al. Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. Leukemia. 2004;18(2):285-292.
19. Nagpal I, Wei L-N. All-trans Retinoic Acid as a Versatile Cytosolic Signal Modulator Mediated by CRABP1. Int J Mol Sci. 2019;20:3610-3620.
20. Prevost N, English JC. Isotretinoin: update on controversial issues. J Pediatr Adolesc Gynecol. 2013;26:290-293.
21. Bauer LB, Ornelas JN, Elston DM, Alikhan A. Isotretinoin: Controversies, facts, and recommendations. Expert Rev Clin Pharmacol. 2016;9(11):1435-1442.
22. Nelson AM, Cong Z, Gilliland KL, Thiboutot DM. TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells. Br J Dermatol. 2011;165:526-533.
23. Kelhälä HL, Fyhrquist N, Palatsi R, Lehtimäki S, Väyrynen JP, Kubin ME, et al. Isotretinoin treatment reduces acne lesions but not directly lesional acne inflammation. Exp Dermatol. 2016;25:477-478.
24. Anvisa [Internet]. Substâncias/ medicamentos controlados: Isotretinoina (Roacutan). [acesso em 2020 Set 7]. Disponível em: http://portal.anvisa.gov.br/anvisa-esclarece?p_p_id=baseconhecimentoportlet_WAR_baseconhecimentoportlet&p_p_lifecycle=0&p_p_state=normal&p_p_mode=view&p_p_col_id=column-2&p_p_col_pos=1&p_p_col_count=2&_baseconhecimentoportlet_WAR_baseconhecimentoportlet_assuntoId=13&_baseconhecimentoportlet_WAR_baseconhecimentoportlet_conteudoId=2572&_baseconhecimentoportlet_WAR_baseconhecimentoportlet_view=detalhamentos
25. Van der Weijden F, Dell’Acqua F, Slot DE. Alveolar bone dimensional changes of post-extraction sockets in humans: a systematic review. J Clin Periodontol. 2009;36:1048-1058.
26. Hupp JR. Reparo de feridas. In: Cirurgia oral e Maxilofacial Contemporânea. Hupp JR, Ellis E, Tucker MR, editors. Rio de Janeiro: Elsevier; 2009. p. 49-60.
27. Rosenberg AE. In: Bones, Joints, and Soft Tissue Tumors. Abbas AK, Robbins SL, Fausto N, Kumar V, editors. Robbins and Cotran pathologic basis of disease. Rio de Janeiro: Elsevier; 2005. p. 1254-1325.
28. Shetty V, Bertolami CN. Wound healing. In: Peterson’s principles of oral and maxillofacial surgery. Ghali GE, Larsen P, Waite P, editors. V1. Canada: BC Decker Inc; 2004. p. 3-17.
29. Yip WL. Influence of oxygen on wound healing. Int Wound J. 2015;12(6):620-4.
30. Sims NA, Martin TJ. Review. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3(481):1-10.
31. Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. 2001;16(9):1575-1582.
32. Henning P, Conaway HH, Lerner UH. Retinoid receptors in bone and their role in bone remodeling. Front Endocrinol. 2015;6(31):1-13.
33. DiGiovanna JJ, Langman CB, Tschen EH, Jones T, Menter A, Lowe NJ et al. Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne. J Am Acad Dermatol. 2004;51(5):709-717.
34. Miziołek B, Bergler-Czop B, Stańkowska A, Brzezińska-Wcisło L. The safety of isotretinoin treatment in patients with bone fractures. Postepy Dermatol Alergol. 2019;36(1):18-24.
35. Rohde C M, Manatt M, Clagett-Dame M, DeLuca H F. Vitamin A antagonizes the action of vitamin D in rats. J. Nutr
Philadelphia. 1999;129(12):2246-2250.
36. Rozenfeld, S. Farmacovigilância: elementos para a discussão e perspectivas. Cadernos de Saúde Pública. 1998;14(2):237-263.
37. Chou R, Aronson N, Atkins D, Ismalia AS, Santaguida P, Smith DH, et al. AHRQ series paper 4: assessing harms when comparing medical interventions: AHRQ and the effective health-care program. J Clin Epidemiol. 2010;63(5):502-512.
38. Moraes SLC, Afonso AMP, Santos RG, Mattos RP, Oliveira MTF, Zanetta-Barbosa D, et al. Riscos e complicações para os ossos da face decorrentes do uso de bisfosfonatos. Rev Bras Odontol. 2013;70(2):114-119.
39. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. Aust Endod J. 2009;35(3):119-130.
2. Chandraratna RAS. Tazarotene, first of a new generation of receptor selective retinoids. Br J Dermatol. 1996;135 Suppl 49:18-25.
3. Hoyos B, Imam A, Chua R, Swenson C, Tong GX, Levi E, et al. The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptor. J Exp Med. 2000;192:835-845.
4. Aggarwal S, Kim SW, Cheon K, Tabassam FH, Yoon JH, Koo S. Nonclassical action of retinoic acid on the activation of the cAMP response element binding protein in normal human bronchial epithelial cells. Mol Biol Cell. 2006;17:566-575.
5. Sewell MJ, Burkhart CN, Morrell DS. Farmacologia dermatológica. In: Brunton LL, Hilal-Dandan R, Knollman B, editors. As bases farmacológicas da terapêutica de Goodman e Gilman. Porto Alegre: AMGH; 2019. p. 1563-1594.
6. Khalil S, Bardawil T, Stephan C, Darwiche N, Abbas O, Kibbi AG, et al. Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects. J Dermatolog Treat. 2017;28(8):684-696.
7. Isotretinoina. [Bula]. Rio de Janeiro: Produtos Roche Químicos e Farmacêuticos S.A.; 2018.
8. Ellis CN; Krach KJ. Uses and complications of isotretinoin therapy. J Am Acad Dermatol. 2001;45(5):S150-157.
9. David J. Margolis, MD; Maurice Attie, MD; James J. Leyden, MD. Effects of isotretinoin on bone mineralization during routine therapy with isotretinoin for acne vulgaris. Dermatol. 1996;132(7):769-774.
10. Bergoli RD. Efeito da isotretinoina no reparo alveolar após exodontia - Estudo em ratos. [Dissertação de Mestrado]. Porto Alegre: Pontifícia Universidade Católica do Rio Grande do Sul; 2009.
11. Oliveira HTR. Efeito da isotretinoina no reparo de defeitos ósseos em calota craniana – estudo em ratos. [Tese de doutorado]. Porto Alegre: Pontifícia Universidade Católica do Rio Grande do Sul; 2009.
12. Cayman Chemical. [Internet]. Vitamin A (20241); Isotretinoin (21648); All-trans retinoic acid (11017); 9-cis-retinoic acid (14587); All-trans-4-hydroxy retinoic acid (21378). [acesso em 2020 Jun 28]. Disponível em: https://www.caymanchem.com/HMRP#:~:text=For%20every%20step%20of%20your,the%20discretion%20of%20Cayman%20Chemical.
13. Szanto A, Narkar V, Shen Q, Uray IP, Davies PJA, Nagy L. Review. Retinoid X Receptors: X-Ploring Their (Patho) Physiological Functions. Cell Death Differ. 2004;11 Suppl 2:S126-143.
14. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992;68(2):397-406.
15. Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, et al. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature. 1992;355:359-361.
16. Layton A. Review. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162-9.
17. Lal L, Li Y, Smith J, Sassano A; Uddin S, Parmar S, et al. Activation of the p70 S6 Kinase by All-Trans-Retinoic Acid in Acute Promyelocytic Leukemia Cells. Blood. 2005;105(4):1669-1677.
18. Zhao Q, Tao J, Zhu Q, Jia PM, Dou AX, Li X, et al. Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. Leukemia. 2004;18(2):285-292.
19. Nagpal I, Wei L-N. All-trans Retinoic Acid as a Versatile Cytosolic Signal Modulator Mediated by CRABP1. Int J Mol Sci. 2019;20:3610-3620.
20. Prevost N, English JC. Isotretinoin: update on controversial issues. J Pediatr Adolesc Gynecol. 2013;26:290-293.
21. Bauer LB, Ornelas JN, Elston DM, Alikhan A. Isotretinoin: Controversies, facts, and recommendations. Expert Rev Clin Pharmacol. 2016;9(11):1435-1442.
22. Nelson AM, Cong Z, Gilliland KL, Thiboutot DM. TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells. Br J Dermatol. 2011;165:526-533.
23. Kelhälä HL, Fyhrquist N, Palatsi R, Lehtimäki S, Väyrynen JP, Kubin ME, et al. Isotretinoin treatment reduces acne lesions but not directly lesional acne inflammation. Exp Dermatol. 2016;25:477-478.
24. Anvisa [Internet]. Substâncias/ medicamentos controlados: Isotretinoina (Roacutan). [acesso em 2020 Set 7]. Disponível em: http://portal.anvisa.gov.br/anvisa-esclarece?p_p_id=baseconhecimentoportlet_WAR_baseconhecimentoportlet&p_p_lifecycle=0&p_p_state=normal&p_p_mode=view&p_p_col_id=column-2&p_p_col_pos=1&p_p_col_count=2&_baseconhecimentoportlet_WAR_baseconhecimentoportlet_assuntoId=13&_baseconhecimentoportlet_WAR_baseconhecimentoportlet_conteudoId=2572&_baseconhecimentoportlet_WAR_baseconhecimentoportlet_view=detalhamentos
25. Van der Weijden F, Dell’Acqua F, Slot DE. Alveolar bone dimensional changes of post-extraction sockets in humans: a systematic review. J Clin Periodontol. 2009;36:1048-1058.
26. Hupp JR. Reparo de feridas. In: Cirurgia oral e Maxilofacial Contemporânea. Hupp JR, Ellis E, Tucker MR, editors. Rio de Janeiro: Elsevier; 2009. p. 49-60.
27. Rosenberg AE. In: Bones, Joints, and Soft Tissue Tumors. Abbas AK, Robbins SL, Fausto N, Kumar V, editors. Robbins and Cotran pathologic basis of disease. Rio de Janeiro: Elsevier; 2005. p. 1254-1325.
28. Shetty V, Bertolami CN. Wound healing. In: Peterson’s principles of oral and maxillofacial surgery. Ghali GE, Larsen P, Waite P, editors. V1. Canada: BC Decker Inc; 2004. p. 3-17.
29. Yip WL. Influence of oxygen on wound healing. Int Wound J. 2015;12(6):620-4.
30. Sims NA, Martin TJ. Review. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3(481):1-10.
31. Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. 2001;16(9):1575-1582.
32. Henning P, Conaway HH, Lerner UH. Retinoid receptors in bone and their role in bone remodeling. Front Endocrinol. 2015;6(31):1-13.
33. DiGiovanna JJ, Langman CB, Tschen EH, Jones T, Menter A, Lowe NJ et al. Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne. J Am Acad Dermatol. 2004;51(5):709-717.
34. Miziołek B, Bergler-Czop B, Stańkowska A, Brzezińska-Wcisło L. The safety of isotretinoin treatment in patients with bone fractures. Postepy Dermatol Alergol. 2019;36(1):18-24.
35. Rohde C M, Manatt M, Clagett-Dame M, DeLuca H F. Vitamin A antagonizes the action of vitamin D in rats. J. Nutr
Philadelphia. 1999;129(12):2246-2250.
36. Rozenfeld, S. Farmacovigilância: elementos para a discussão e perspectivas. Cadernos de Saúde Pública. 1998;14(2):237-263.
37. Chou R, Aronson N, Atkins D, Ismalia AS, Santaguida P, Smith DH, et al. AHRQ series paper 4: assessing harms when comparing medical interventions: AHRQ and the effective health-care program. J Clin Epidemiol. 2010;63(5):502-512.
38. Moraes SLC, Afonso AMP, Santos RG, Mattos RP, Oliveira MTF, Zanetta-Barbosa D, et al. Riscos e complicações para os ossos da face decorrentes do uso de bisfosfonatos. Rev Bras Odontol. 2013;70(2):114-119.
39. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. Aust Endod J. 2009;35(3):119-130.