Efeito do ácido zoledrônico na movimentação dentária induzida em ratos

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Sousa, Fátima Regina Nunes
Orientador(a): Leitão, Renata Ferreira de Carvalho
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/33103
Resumo: Zoledronic acid (ZA) is a potent bisphosphonate that binds to the hydroxyapatite of the bone surface and acts preferentially in sites of bone formation and resorption, being used in the treatment of bone pathologies. This study aims to evaluate the effects of Zoledronic Acid (ZA) during induced tooth movement (OTM) in rats, in an experimental model that simulates the doses and route of administration of ZA in patients treated with bone metabolic disorders. Wistar rats (180-220 g) divided into two experimental phases were used. In the first phase, different periods of ITM were evaluated (1,4,7,11,14 and 21 days), in order to determine the ideal day to study the effect of ZA. NiTi springs were installed in the first left maxillary molar with 50N allowing the ITM. The maxilla was removed Histological and histometric analyzes of bone and tooth root were performed. On day 21 greater root resorption and tooth displacement were observed, and on day 4, more osteoclasts and necrotic areas were observed when compared to day 0 (p <0.05). In the second phase, four groups were divided: Naive (N), Saline (SAL), Zoledronic Acid with a concentration of 0.2 mg/kg (ZA/0,2) and Zoledronic Acid with a concentration of 1.0 mg /kg/ (ZA/1.0). All groups, except naive, were submitted to NiTi springs installation in the first left maxillary molar with a force of 50g allowing ITM for a period of 4 and 21 days. Administration of ZA (0.2 and 1.0 mg/kg, iv) was performed for 3 consecutive weeks and on day 42, just before the insertion of the springs. These animals were euthanized on days 46 and 63. Jaws were removed for macroscopic and histopathological analyzes (using HE, Picrosirius Red, Mallory), scanning electron microscopy (SEM), computerized microtomography and confocal microscopy. The following parameters were analyzed: bone and root resorption, tooth movement, collagen analysis and blood vessel count. Blood samples were collected for biochemical measurements of alkaline phosphatase, phosphorus and calcium. Treatment with ZA decreased the ITM and the number of osteoclasts and loss of alveolar bone when compared to the naive and saline groups (p <0.05). Treatment with ZA also increased necrotic areas in the periodontal ligament and reduced vascularization (p <0.05). Reduction of radicular resorption was observed in the groups treated with ZA when compared with the saline group. There were no significant changes in the percentage of type I collagen and III between the saline and ZA groups, at any of the concentrations used. In summary, the results of this study show that ZA interferes with ITM and presents anti-resorptive effects on bone and dental tissues associated with decreased of vessel numbers without osteonecrosis. The use of zoledronic acid, therefore, is not a risk factor for the development of maxillary osteonecrosis in the experimental model of ITM used in the present study.
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spelling Sousa, Fátima Regina NunesLeitão, Renata Ferreira de Carvalho2018-06-20T18:34:54Z2018-06-20T18:34:54Z2018-06-20SOUSA, F. R. N. Efeito do ácido zoledrônico na movimentação dentária induzida em ratos. 2018. 108 f. Tese (Doutorado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/33103Zoledronic acid (ZA) is a potent bisphosphonate that binds to the hydroxyapatite of the bone surface and acts preferentially in sites of bone formation and resorption, being used in the treatment of bone pathologies. This study aims to evaluate the effects of Zoledronic Acid (ZA) during induced tooth movement (OTM) in rats, in an experimental model that simulates the doses and route of administration of ZA in patients treated with bone metabolic disorders. Wistar rats (180-220 g) divided into two experimental phases were used. In the first phase, different periods of ITM were evaluated (1,4,7,11,14 and 21 days), in order to determine the ideal day to study the effect of ZA. NiTi springs were installed in the first left maxillary molar with 50N allowing the ITM. The maxilla was removed Histological and histometric analyzes of bone and tooth root were performed. On day 21 greater root resorption and tooth displacement were observed, and on day 4, more osteoclasts and necrotic areas were observed when compared to day 0 (p <0.05). In the second phase, four groups were divided: Naive (N), Saline (SAL), Zoledronic Acid with a concentration of 0.2 mg/kg (ZA/0,2) and Zoledronic Acid with a concentration of 1.0 mg /kg/ (ZA/1.0). All groups, except naive, were submitted to NiTi springs installation in the first left maxillary molar with a force of 50g allowing ITM for a period of 4 and 21 days. Administration of ZA (0.2 and 1.0 mg/kg, iv) was performed for 3 consecutive weeks and on day 42, just before the insertion of the springs. These animals were euthanized on days 46 and 63. Jaws were removed for macroscopic and histopathological analyzes (using HE, Picrosirius Red, Mallory), scanning electron microscopy (SEM), computerized microtomography and confocal microscopy. The following parameters were analyzed: bone and root resorption, tooth movement, collagen analysis and blood vessel count. Blood samples were collected for biochemical measurements of alkaline phosphatase, phosphorus and calcium. Treatment with ZA decreased the ITM and the number of osteoclasts and loss of alveolar bone when compared to the naive and saline groups (p <0.05). Treatment with ZA also increased necrotic areas in the periodontal ligament and reduced vascularization (p <0.05). Reduction of radicular resorption was observed in the groups treated with ZA when compared with the saline group. There were no significant changes in the percentage of type I collagen and III between the saline and ZA groups, at any of the concentrations used. In summary, the results of this study show that ZA interferes with ITM and presents anti-resorptive effects on bone and dental tissues associated with decreased of vessel numbers without osteonecrosis. The use of zoledronic acid, therefore, is not a risk factor for the development of maxillary osteonecrosis in the experimental model of ITM used in the present study.O ácido zoledrônico (AZ) é um potente bisfosfonato que se liga fortemente à hidroxiapatita da superfície óssea e atua preferencialmente em sítios de grande formação e reabsorção óssea, sendo utilizado no tratamento de patologias ósseas. Este estudo objetiva avaliar os efeitos do Ácido Zoledrônico (AZ) durante a movimentação dentária induzida (MDI) em ratos, em um modelo experimental que simula as doses e via de administração do AZ de pacientes tratados com desordens metabólicas ósseas. Foram utilizados 83 ratos Wistar (180-220 g) divididos em duas fases experimentais. Na primeira fase foram avaliados diferentes períodos de MDI (1,4,7,11,14 e 21 dias), com finalidade de avaliar o dia ideal para estudar o efeito do AZ. Foram instaladas molas de NiTi no primeiro molar superior esquerdo com força de 50gf permitindo a MDI. Os animais foram sacrificados e a maxila foi removida para análises histológicas e histométricas óssea e radicular. O dia 21 houve maior reabsorção radicular e deslocamento dentário e o dia 4 maior número de osteoclastos e áreas hialínicas quando comparado ao dia 0 (p<0,05). Na segunda fase os animais foram divididos em 04 grupos: Naive (N), Salina (SAL), Ácido Zoledrônico com concentração de 0,2 mg/kg (AZ/0,2) e Ácido Zoledrônico com concentração de 1,0 mg/kg (AZ/1,0). Todos os grupos, exceto o naive foram instaladas molas de NiTi no primeiro molar superior esquerdo com força de 50gf permitindo a MDI por um período de 4 e 21 dias. A administração do AZ (0,2 e 1,0 mg/kg, i.v) foi realizada durante 3 semanas consecutivas e a última dose no D42 com a MDI. Estes animais foram eutanasiados no D46 e D63. As maxilas foram removidas para análises macroscópica, histopatológica, histométrica, por microscopia eletrônica de varredura (MEV), microtomografia computadorizada, análise do percentual de perda óssea por microscopia confocal, análise de colágeno por coloração de Picrosirius Red sob luz polarizada, análise dos vasos sanguíneos por coloração de Mallory, e amostras sanguíneas foram coletadas para dosagens bioquímicas. O tratamento com AZ diminuiu a MDI, osteoclastos e nível de perda óssea no osso alveolar quando comparado ao grupo naive e salina (p<0,05). No ligamento periodontal observou-se aumento das áreas hialínicas no lado de compressão e redução da vascularização no lado de tração (p<0,05). No MEV, verificou-se redução da reabsorção radicular nos grupos tratados com AZ quando comprado com o grupo salina. O tratamento com AZ não alterou o percentual de colágeno tipo I e III, mas reduziu os níveis de cálcio e fosfatase alcalina quando comparado ao naive (p<0,05). Em suma, os resultados deste estudo mostraram que o AZ interfere na MDI, apresentando seus efeitos anti-reabsortivos a nível ósseo e dentário, e que embora seja visualizado efeito na redução da vascularização, a estrutura óssea foi preservada com vitalidade das células, desta forma o uso do ácido zoledrônico não é um fator de risco para a osteonecrose da maxila no modelo experimental em ratos.DifosfonatosTécnicas de Movimentação DentáriaReabsorção da RaizEfeito do ácido zoledrônico na movimentação dentária induzida em ratosEffect of zoledronic acid on induced tooth movement in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81812http://repositorio.ufc.br/bitstream/riufc/33103/2/license.txt9351db63ea91b32e01910aaf21c0fd0aMD52ORIGINAL2018_tese_frnsousa.pdf2018_tese_frnsousa.pdfapplication/pdf5287722http://repositorio.ufc.br/bitstream/riufc/33103/1/2018_tese_frnsousa.pdf5424c17146e20b21988080b5b7ebc407MD51riufc/331032018-12-14 10:25:02.748oai:repositorio.ufc.br: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ório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2018-12-14T13:25:02Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
dc.title.en.pt_BR.fl_str_mv Effect of zoledronic acid on induced tooth movement in rats
title Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
spellingShingle Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
Sousa, Fátima Regina Nunes
Difosfonatos
Técnicas de Movimentação Dentária
Reabsorção da Raiz
title_short Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
title_full Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
title_fullStr Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
title_full_unstemmed Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
title_sort Efeito do ácido zoledrônico na movimentação dentária induzida em ratos
author Sousa, Fátima Regina Nunes
author_facet Sousa, Fátima Regina Nunes
author_role author
dc.contributor.author.fl_str_mv Sousa, Fátima Regina Nunes
dc.contributor.advisor1.fl_str_mv Leitão, Renata Ferreira de Carvalho
contributor_str_mv Leitão, Renata Ferreira de Carvalho
dc.subject.por.fl_str_mv Difosfonatos
Técnicas de Movimentação Dentária
Reabsorção da Raiz
topic Difosfonatos
Técnicas de Movimentação Dentária
Reabsorção da Raiz
description Zoledronic acid (ZA) is a potent bisphosphonate that binds to the hydroxyapatite of the bone surface and acts preferentially in sites of bone formation and resorption, being used in the treatment of bone pathologies. This study aims to evaluate the effects of Zoledronic Acid (ZA) during induced tooth movement (OTM) in rats, in an experimental model that simulates the doses and route of administration of ZA in patients treated with bone metabolic disorders. Wistar rats (180-220 g) divided into two experimental phases were used. In the first phase, different periods of ITM were evaluated (1,4,7,11,14 and 21 days), in order to determine the ideal day to study the effect of ZA. NiTi springs were installed in the first left maxillary molar with 50N allowing the ITM. The maxilla was removed Histological and histometric analyzes of bone and tooth root were performed. On day 21 greater root resorption and tooth displacement were observed, and on day 4, more osteoclasts and necrotic areas were observed when compared to day 0 (p <0.05). In the second phase, four groups were divided: Naive (N), Saline (SAL), Zoledronic Acid with a concentration of 0.2 mg/kg (ZA/0,2) and Zoledronic Acid with a concentration of 1.0 mg /kg/ (ZA/1.0). All groups, except naive, were submitted to NiTi springs installation in the first left maxillary molar with a force of 50g allowing ITM for a period of 4 and 21 days. Administration of ZA (0.2 and 1.0 mg/kg, iv) was performed for 3 consecutive weeks and on day 42, just before the insertion of the springs. These animals were euthanized on days 46 and 63. Jaws were removed for macroscopic and histopathological analyzes (using HE, Picrosirius Red, Mallory), scanning electron microscopy (SEM), computerized microtomography and confocal microscopy. The following parameters were analyzed: bone and root resorption, tooth movement, collagen analysis and blood vessel count. Blood samples were collected for biochemical measurements of alkaline phosphatase, phosphorus and calcium. Treatment with ZA decreased the ITM and the number of osteoclasts and loss of alveolar bone when compared to the naive and saline groups (p <0.05). Treatment with ZA also increased necrotic areas in the periodontal ligament and reduced vascularization (p <0.05). Reduction of radicular resorption was observed in the groups treated with ZA when compared with the saline group. There were no significant changes in the percentage of type I collagen and III between the saline and ZA groups, at any of the concentrations used. In summary, the results of this study show that ZA interferes with ITM and presents anti-resorptive effects on bone and dental tissues associated with decreased of vessel numbers without osteonecrosis. The use of zoledronic acid, therefore, is not a risk factor for the development of maxillary osteonecrosis in the experimental model of ITM used in the present study.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-06-20T18:34:54Z
dc.date.available.fl_str_mv 2018-06-20T18:34:54Z
dc.date.issued.fl_str_mv 2018-06-20
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dc.identifier.citation.fl_str_mv SOUSA, F. R. N. Efeito do ácido zoledrônico na movimentação dentária induzida em ratos. 2018. 108 f. Tese (Doutorado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/33103
identifier_str_mv SOUSA, F. R. N. Efeito do ácido zoledrônico na movimentação dentária induzida em ratos. 2018. 108 f. Tese (Doutorado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
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