The influence of the selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram on the regeneration process
DOI:
https://doi.org/10.33448/rsd-v10i17.24319Keywords:
Sertraline; Fluoxetine; Citalopram; Bone regeneration; Fracture healing.Abstract
Although bone tissue regeneration is a well-defined process, complications inherent to the treatment of fractures are still observed, one of them being the participation of serotonin in bone formation and remodeling. This is a hormone responsible for the regulation of several physiological processes and is correlated with the etiology of depression, whose treatment is given, especially, through the use of selective serotonin reuptake inhibitors (SSRI), which are related to an increased risk of fracture and bone loss. Thus, the aim of this study was to analyze the action of Fluoxetine, Sertraline and Citalopram in the bone regeneration process. Thirty-five Wistar rats were used, in which bone defects of 2 to 3 mm in length were made in the fibula. The animals received Fluoxetine Hydrochloride 60 days before the fracture was made, and Sertraline Hydrochloride and Citalopram Hydrochloride 40 days before, and continued for another 30 days after the procedure. Control animals received saline solution. The results show that the bone defect regeneration process occurred more effectively in animals belonging to the control group, when compared to the other treated groups. The same data were observed regarding the serum alkaline phosphatase rate, statistically different when compared to animals treated with SSRIs. These data allow us to suggest that Fluoxetine, Sertraline and Citalopram seem to negatively interfere in the bone regeneration process, leading to a delay and non-complete consolidation of fractures with bone loss.
References
Abu Nada, L. (2017). The effect of selective serotonin reuptake inhibitors on bone healing and titanium implant osseointegration. EScholarship@McGill. https://escholarship.mcgill.ca/concern/theses/h702q874b
Abu Nada, L., Al Subaie, A., Mansour, A., Wu, X., Abdallah, M., Al‐Waeli, H., Ersheidat, A., Stone, L. S., Murshed, M., & Tamimi, F. (2018). The antidepressant drug, sertraline, hinders bone healing and osseointegration in rats’ tibiae. Journal of Clinical Periodontology, 45(12), 1485–1497. https://doi.org/10.1111/jcpe.13015
Atli, O., Baysal, M., Aydogan-Kilic, G., Kilic, V., Ucarcan, S., Karaduman, B., & Ilgin, S. (2017). Sertraline-induced reproductive toxicity in male rats: evaluation of possible underlying mechanisms. Asian Journal of Andrology, 19(6), 672. https://doi.org/10.4103/1008-682x.192637
Brandão, M. M. C. (2015) Influência do uso de fármacos anti-depressivos na colocação de implantes dentários. Cidade do Porto, 2015.
Cray, J. J., Weinberg, S. M., Parsons, T. E., Howie, R. N., Elsalanty, M., & Yu, J. C. (2014). Selective serotonin reuptake inhibitor exposure alters osteoblast gene expression and craniofacial development in mice. Birth Defects Research Part A: Clinical and Molecular Teratology, 100(12), 912–923. https://doi.org/10.1002/bdra.23323
Cuquetto, D. C., Mill, J. G., & Amaral, F. T. do. (2012). Influência do uso de fluoxetina sobre o tempo de corrida em esteira ergométrica em ratos não treinados. Revista Brasileira de Educação Física E Esporte, 26(3), 375–381. https://doi.org/10.1590/s1807-55092012000300003
Ducy, P. (2011). 5-HT and bone biology. Current Opinion in Pharmacology, 11(1), 34–38. https://doi.org/10.1016/j.coph.2011.01.007
Ducy, P., & Karsenty, G. (2010). The two faces of serotonin in bone biology. Journal of Cell Biology, 191(1), 7–13. https://doi.org/10.1083/jcb.201006123
Feighner, J. P., & Overø, K. (1999). Multicenter, Placebo-Controlled, Fixed-Dose Study of Citalopram in Moderate-to-Severe Depression. The Journal of Clinical Psychiatry, 60(12), 824–830. https://doi.org/10.4088/jcp.v60n1204
Fernandes, E. V., Ramos, S. de P., Estanislau, C., & Venancio, E. J. (2012). Efeitos comportamentais e imunológicos da fluoxetina em ratos submetidos ao nado forçado. Psicologia: Teoria E Pesquisa, 28(4), 409–415. https://doi.org/10.1590/s0102-37722012000400008
Fleck, M. P., Berlim, M. T., Lafer, B., Sougey, E. B., Porto, J. A. D., Brasil, M. A., Juruena, M. F., & Hetem, L. A. (2009). Revisão das diretrizes da Associação Médica Brasileira para o tratamento da depressão (Versão integral). Brazilian Journal of Psychiatry, 31, S7–S17. https://doi.org/10.1590/S1516-44462009000500003
Fleck, M. P., Berlim, M. T., Lafer, B., Sougey, E. B., Porto, J. A. D., Brasil, M. A., Juruena, M. F., & Hetem, L. A. (2009). Revisão das diretrizes da Associação Médica Brasileira para o tratamento da depressão (Versão integral). Brazilian Journal of Psychiatry, 31, S7–S17. https://doi.org/10.1590/S1516-44462009000500003
Fonseca, D. D. D. (2020). Efeitos da fluoxetina sobre a odontogênese e o desenvolvimento dos tecidos mineralizados dos dentes [Tese de doutorado].
Garlingo, LCM. Williams, JN, Li, Y., Valiya Kambrath, A., & Sankar, U. (2018). A geração de fraturas femorais fechadas em camundongos: um modelo para estudar a cura óssea. Jornal de experimentos visualizados: JoVE, (138), 58122. https://doi.org/10.3791/58122. CSS. Patologia. Universidade Federal de Pernambuco, 2006. (sd). [Tese de mestrado].
Gartner, L. P. Hiatt, J. L., & Al, E. (2007). Tratado de histologia em cores. Elsevier.
Gill, J. S., Jamwal, S., Kumar, P., & Deshmukh, R. (2017). Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington’s like symptoms in rats: Possible neurotransmitters modulation. Pharmacological Reports: PR, 69(2), 306–313. https://doi.org/10.1016/j.pharep.2016.11.008
Gonçalves, P. C. (2013) Efeitos do tratamento com cloridrato de fluoxetina na mandíbula da prole de ratas tratadas durante a gestação e lactação. (Dissertação de Mestrado). Universidade Federal de Pernambuco.
Henn, JD (2010). Bioquímica Do Tecido Ósseo 1. https://www.ufrgs.com.br/lacvet/restrito/pdf/osso_henn.pdf
Hodge, J. M., Wang, Y., Berk, M., Collier, F. M., Fernandes, T. J., Constable, M. J., Pasco, J. A., Dodd, S., Nicholson, G. C., Kennedy, R. L., & Williams, L. J. (2013). Selective Serotonin Reuptake Inhibitors Inhibit Human Osteoclast and Osteoblast Formation and Function. Biological Psychiatry, 74(1), 32–39. https://doi.org/10.1016/j.biopsych.2012.11.003
Howie, R. N., Herberg, S., Durham, E., Grey, Z., Bennfors, G., Elsalanty, M., LaRue, A. C., Hill, W. D., & Cray, J. J. (2018). Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model. International Journal of Oral Science, 10(3), 25. https://doi.org/10.1038/s41368-018-0026-x
Isola, J. G. M. P., & Moraes, P. C. (2012). Estrutura e regeneração óssea - revisão de literatura. Revista científica eletrônica de Medicina Veterinária , 18.
Jaegger, IMS (2015, 21 de maio). Aspectos morfológicos e imunohistoquímico da dentinogênese e pulpogênese em prol de ratas tratadas com fluoxetina durante a gestação e lactação. Repositório. ufpe.br. https://repositorio.ufpe.br/handle/123456789/16252
Junqueira, LCU & Carneiro, J. (2013). Histologia Básica Texto e Atlas (12ed)
Li, I-Hsun., Shih, J.-H., Jhao, Y.-T., Chen, H.-C., Chiu, C.-H., Chen, C.-F., Huang, Y.-S., Shiue, C.-Y., & Ma, K.-H. (2019). Regulation of Noise-Induced Loss of Serotonin Transporters with Resveratrol in a Rat Model Using 4-[18F]-ADAM/Small-Animal Positron Emission Tomography. Molecules, 24(7), 1344. https://doi.org/10.3390/molecules24071344
Lirani, A. P. R. Estudo comparativo dos efeitos do ultra-som e do laser de baixa intensidade no reparo ósseo de tíbia de rato. https://doi.org/10.11606/d.82.2004.tde-04052004-091046
Matos, J. A. de B. (2011). Aspectos morfológicos do desenvolvimento do osso alveolar de filhotes de ratas tratadas com fluoxetina durante a gestação. Repositorio.ufpe.br. https://repositorio.ufpe.br/handle/123456789/8325
Mir, M., Pereira, M. A., Geonmonond, R. S., Oliveira, U. S., Araújo, T. H., & Rossi, W. C. (2013). Uso de hidroxiapatita nanométrica em enxertos na fíbula de ratos. Ciência et Praxis, 6(11), 21–24. https://revista.uemg.br/index.php/praxys/article/view/2116
Rapport, M. M., Green, A. A., & Page, I. H. (1948). Serum Vasoconstrictor (SEROTONIN). Journal of Biological Chemistry, 176(3), 1243–1251. https://doi.org/10.1016/s0021-9258(18)57137-4
Refsgaard, L. K., Haubro, K., Pickering, D. S., Stuart, S. A., Robinson, E. S. J., & Andreasen, J. T. (2016). Effects of sertraline, duloxetine, vortioxetine, and idazoxan in the rat affective bias test. Psychopharmacology, 233(21-22), 3763–3770. https://doi.org/10.1007/s00213-016-4407-6
Regueira, L. S. (2013). Efeitos da fluoxetina na periodontogênese: Análise histológica e histomorfométrica em ratos. Repositorio.ufpe.br. https://repositorio.ufpe.br/handle/123456789/13120
Richter, T., Paluch, Z., & Alusik, S. (2014). The non-antidepressant effects of citalopram: a clinician’s perspective. Neuro Endocrinology Letters, 35(1), 7–12. https://pubmed.ncbi.nlm.nih.gov/24625921/
Riksen, E. A., Stunes, A. K., Kalvik, A., Gustafsson, B. I., Snead, M. L., Syversen, U., Lyngstadaas, S. P., & Reseland, J. E. (2010). Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells and modulate gene expression in LS8 cells. European Journal of Oral Sciences, 118(6), 566–573. https://doi.org/10.1111/j.1600-0722.2010.00778.x
Rossi Jr, W. C. (2002). Influência de uma membrana de colágeno associada a extrato etanólico de própolis na consolidação de fraturas com perda óssea (Disssertação de Doutorado). Universidade Estadual de Campinas.
Santiago, I. M. A., Regueira, L. S., Correia, P. G., Alcântara, R. J. B., Evêncio, J. N., & Baratella-Evêncio, L. (2013) Effects of The Use of Fluoxetine Hydrochloride on the Development of Mineralized Tissues in Rats: a Systematic Review. R bras ci Saúde 17(2):181-188.
Seibel, M. J., Robins, S. P., & Bilezikian, J. P. (2006). Dynamics of bone and cartilage metabolism: [principles and clinical applications]. Academic Press.
Silva, F. S. (2016). Hidroxiapatita carbonatada e plasma rico em plaquetas em enxertos ósseos (Dissertação de Mestrado). Universidade Federal de Alfenas.
Tarabar, A. F., Hoffman, R. S., & Nelson, L. S. (2008). Citalopram overdose: Late presentation of torsades de pointes (TdP) with cardiac arrest. Journal of Medical Toxicology, 4(2), 101–105. https://doi.org/10.1007/bf03160963
Telles-Correia, D., Guerreiro, D. F., Oliveira, S., & Figueira, M. L. (2007). Diferenças farmacodinâmicas e farmacocinéticas entre os SSRI: implicações na prática clínica [Differences between SSRI's pharmacokinetics and pharmacodinamics]. Acta medica portuguesa, 20(2), 167–174.
Vestergaard, P., Rejnmark, L., & Mosekilde, L. (2008). Selective Serotonin Reuptake Inhibitors and Other Antidepressants and Risk of Fracture. Calcified Tissue International, 82(2), 92–101. https://doi.org/10.1007/s00223-007-9099-9
Viera, A; Varotto P, V; Roim B, L; D'ottaviano R; & Antequera, R. (2018). O efeito dos inibidores seletivos da recaptação da serotonina no metabolismo ósseo e sua influência na odontologia. ImplantNews Perio. v3(4): 675-680.
Warden, S. J., Robling, A. G., Sanders, M. S., Bliziotes, M. M., & Turner, C. H. (2005). Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology, 146(2), 685–693. https://doi.org/10.1210/en.2004-1259
Williams, L. J., Berk, M., Hodge, J. M., Kotowicz, M. A., Stuart, A. L., Chandrasekaran, V., Cleminson, J., & Pasco, J. A. (2018). Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men. Calcified Tissue International, 103(2), 125–130. https://doi.org/10.1007/s00223-018-0398-0
Yadav, V. K., Oury, F., Suda, N., Liu, Z. W., Gao, X. B., Confavreux, C., Klemenhagen, K. C., Tanaka, K. F., Gingrich, J. A., Guo, X. E., Tecott, L. H., Mann, J. J., Hen, R., Horvath, T. L., & Karsenty, G. (2009). A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell, 138(5), 976–989. https://doi.org/10.1016/j.cell.2009.06.051
Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schütz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., & Karsenty, G. (2008). Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum. Cell, 135(5), 825–837. https://doi.org/10.1016/j.cell.2008.09.059
Yildirim, G., & Eralp, F. E. (2021). Effect of Antidepressants and its Orthodontic Implications. Essentials of Dentistry. https://doi.org/10.5152/essentdent.2021.21005
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Letícia da Costa Siqueira; Karinne da Costa Souza; Micaella Rodrigues Guimarães Leite; Ítalo Augusto Silva Ferreira; Ana Luiza Dias Leite de Andrade; Alessandra Esteves; Wagner Costa Rossi Junior
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
