Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar
Ano de defesa: | 2021 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Odontológicas
|
Departamento: |
Odontologia
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País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/21150 |
Resumo: | Osteonecrosis is a bone pathology, with a still unknown etiopathogenesis, which was first reported in 2003 by Marx. In 2014 the Association of Oral and Maxillofacial Surgeons (AAOMS) described the concept of osteonecrosis, as an area of bone exposure in the jaw or jaw that does not repair in eight weeks due to a temporary or permanent loss of blood supply at the site. It affects, in most cases, patients who chronically use antiresorptive drugs and some associated factors such as corticosteroid therapy, diabetes mellitus, tooth extraction and other invasive dental procedures. Recent work investigates in rats the osteonecrosis induced by these drugs, such as alendronate (AL), zoledronic acid (Z) and denosumab (Dmab), in order to clarify the etiopathogenesis, as well as to study means of prevention and treatment of the disease. the aim of this study was to compare antiresorptive drugs in an animal model in MRONJ rats, using three different antiresorptive drugs: alendronate, zoledronic acid and denosumab, one for each experimental group, based on the clinical and histological parameters of the region undergoing extraction. The clinical parameters evaluated were: area of bone exposure, fistula, poor healing of soft tissue and inflammation in the alveolus. The histological parameters included the analysis of bone necrosis, inflammatory infiltrate (qualitative and quantitative analysis), blood vessels (quantitative analysis), bone sequestration and root rest. There were 35 male Wistar rats, randomized into 6 groups: Negative Control Group (CN) physiological saline therapy: GNZ (n = 6), GNAL (n = 6), GNDmab (n = 5); Alendronate Group (GAL) therapy with AL (n = 6); Zometa Group (GZ) Z therapy (n = 6); Denosumab Group (GDmab) Dmab therapy (n = 6). The dose applied to each animal will be according to its weekly weight, following the ratio: GAL 1 mg / Kg - subcutaneous, GZ 0.06mg / kgintraperitoneal and GDmab 0.25mg / kg - intraperitoneal. The GAL group was submitted to 8 applications of LA for a period of 8 weeks (1 weekly application), when completing the eighth week the rats were submitted to tooth extraction. And after 28 days of tooth extraction, they were euthanized, along with 6 rats from the GNAL group. The medication was maintained, once a week, until euthanasia (thirteenth week) for the GAL group. The GZ group received Z four times a week, for four weeks, when the fourth week was completed, tooth extraction was performed, after which the 28-day period was awaited for the euthanasia of the animals in the respective group and another 6 in the GNZ group. The GDmab group received a total of 8 applications of Dmab, for a period of 4 weeks (2 weekly applications), when the fourth week was completed, the animals in the group underwent dental extraction and after 28 days were euthanized, together with the 6 remaining rats from the GNDmab group. The statistical analysis for qualitative variables was used Fisher's exact test, and for the analysis of quantitative variables, One-way ANOVA with Tukey's post hoc was used. Considering a significance level of 0.05. Our results demonstrated a higher prevalence of histological osteonecrosis in the group in the BFs when compared to the Denosumab group, as well as the decrease in the number of vessels was more frequent in the groups of the BFs. Thus, we conclude that, due to the decrease in angiogenesis and the increase in MRONJ in bone tissue, bisphosphonates have a greater alteration in the bone mechan |
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2021-06-18T17:31:47Z2021-06-18T17:31:47Z2021-01-14http://repositorio.ufsm.br/handle/1/21150Osteonecrosis is a bone pathology, with a still unknown etiopathogenesis, which was first reported in 2003 by Marx. In 2014 the Association of Oral and Maxillofacial Surgeons (AAOMS) described the concept of osteonecrosis, as an area of bone exposure in the jaw or jaw that does not repair in eight weeks due to a temporary or permanent loss of blood supply at the site. It affects, in most cases, patients who chronically use antiresorptive drugs and some associated factors such as corticosteroid therapy, diabetes mellitus, tooth extraction and other invasive dental procedures. Recent work investigates in rats the osteonecrosis induced by these drugs, such as alendronate (AL), zoledronic acid (Z) and denosumab (Dmab), in order to clarify the etiopathogenesis, as well as to study means of prevention and treatment of the disease. the aim of this study was to compare antiresorptive drugs in an animal model in MRONJ rats, using three different antiresorptive drugs: alendronate, zoledronic acid and denosumab, one for each experimental group, based on the clinical and histological parameters of the region undergoing extraction. The clinical parameters evaluated were: area of bone exposure, fistula, poor healing of soft tissue and inflammation in the alveolus. The histological parameters included the analysis of bone necrosis, inflammatory infiltrate (qualitative and quantitative analysis), blood vessels (quantitative analysis), bone sequestration and root rest. There were 35 male Wistar rats, randomized into 6 groups: Negative Control Group (CN) physiological saline therapy: GNZ (n = 6), GNAL (n = 6), GNDmab (n = 5); Alendronate Group (GAL) therapy with AL (n = 6); Zometa Group (GZ) Z therapy (n = 6); Denosumab Group (GDmab) Dmab therapy (n = 6). The dose applied to each animal will be according to its weekly weight, following the ratio: GAL 1 mg / Kg - subcutaneous, GZ 0.06mg / kgintraperitoneal and GDmab 0.25mg / kg - intraperitoneal. The GAL group was submitted to 8 applications of LA for a period of 8 weeks (1 weekly application), when completing the eighth week the rats were submitted to tooth extraction. And after 28 days of tooth extraction, they were euthanized, along with 6 rats from the GNAL group. The medication was maintained, once a week, until euthanasia (thirteenth week) for the GAL group. The GZ group received Z four times a week, for four weeks, when the fourth week was completed, tooth extraction was performed, after which the 28-day period was awaited for the euthanasia of the animals in the respective group and another 6 in the GNZ group. The GDmab group received a total of 8 applications of Dmab, for a period of 4 weeks (2 weekly applications), when the fourth week was completed, the animals in the group underwent dental extraction and after 28 days were euthanized, together with the 6 remaining rats from the GNDmab group. The statistical analysis for qualitative variables was used Fisher's exact test, and for the analysis of quantitative variables, One-way ANOVA with Tukey's post hoc was used. Considering a significance level of 0.05. Our results demonstrated a higher prevalence of histological osteonecrosis in the group in the BFs when compared to the Denosumab group, as well as the decrease in the number of vessels was more frequent in the groups of the BFs. Thus, we conclude that, due to the decrease in angiogenesis and the increase in MRONJ in bone tissue, bisphosphonates have a greater alteration in the bone mechanA osteonecrose é uma patologia óssea, com etiopatogenia ainda desconhecida, que foi relatada pela primeira vez em 2003 por Marx. Em 2014 a Association of Oral and Maxillofacial Surgeons (AAOMS) descreveu o conceito da osteonecrose, como sendo uma área de exposição óssea na maxila ou mandíbula que não repara em oito semanas devido a uma perda temporária ou permanente de suprimento sanguíneo no local. Acomete, na maioria dos casos, pacientes que utilizam, cronicamente, medicamentos antirreabsortivos e alguns fatores associados como corticoterapia, diabetes mellitus, exodontia e demais procedimentos odontológicos invasivos. Trabalhos recentes investigam em ratos a osteonecrose induzida por esses medicamentos como o alendronato (AL), ácido zoledrônico (Z) e o denosumab (Dmab), a fim de, esclarecer a etiopatogenia, assim como, estudar meios de prevenção e tratamento da doença. o objetivo deste estudo foi comparar as drogas antirreabsortivas em um modelo animal em ratos de MRONJ, utilizando três diferentes fármacos antirreabsortivos: alendronato, ácido zoledrônico e denosumab, uma para cada grupo experimental, baseado nos parâmetros clínicos e histológicos da região submetida à exodontia. Os parâmetros clínicos avaliados foram: área de exposição óssea, fístula, má cicatrização de tecido mole e inflamação no alvéolo. Já os parâmetros histológicos compreenderam a análise de necrose óssea, infiltrado inflamatório (análise qualitativa e quantitativa), vasos sanguíneos (análise quantitativa), sequestro ósseo e resto radicular. Foram 35 ratos machos Wistar, randomizados em 6 grupos: Grupo Controle Negativo (CN) terapia com solução salina fisiológica: GNZ (n=6), GNAL (n=6), GNDmab (n=5); Grupo Alendronato (GAL) terapia com AL (n=6); Grupo Zometa (GZ) terapia com Z (n=6); Grupo Denosumab (GDmab) terapia com Dmab (n=6). A dose aplicada em cada animal será de acordo com seu peso semanal, seguindo a relação: GAL 1 mg/Kg – subcutânea, GZ 0,06mg/kg- intraperitoneal e GDmab 0,25mg/kg – intraperitoneal. O grupo GAL foi submetido a 8 aplicações de AL por um período de 8 semanas (1 aplicação semanal), ao completar a oitava semana os ratos foram submetidos a extração dentária. E após 28 dias da extração dentária foram eutanasiados, juntamente com 6 ratos do grupo GNAL. A medicação foi mantida, 1 vez na semana, até a eutanásia (décima terceira semana) para o grupo GAL. O grupo GZ recebeu o Z quatro vezes por semana, por quatro semanas, quando completou a quarta semana foi realizado a extração dentária, posteriormente foi aguardado o período de 28 dias para a realização da eutanásia dos animais do respectivo grupo e mais 6 do grupo GNZ. O grupo GDmab recebeu um total de 8 aplicações de Dmab, por um período de 4 semanas (2 aplicações semanais), quando completou a quarta semana os animais do grupo foram submetidos a extração dentária e depois de 28 dias foram eutanasiados, juntamente com os 6 ratos restantes do grupo GNDmab. A análise estatística para as variáveis qualitativas foi utilizada o teste exato de Fisher, e para a análise das variáveis quantitativas foi utilizado One-way ANOVA com post hoc de Tukey. Considerando um nível de significância de 0,05. Nossos resultados demonstraram uma maior prevalência de osteonecrose histológica no grupo nos BF’s quando comparado ao grupo do Denosumab, bem como a diminuição do número de vasos foi mais frequente nos grupos do BFs. Com isso, concluímos que, pela diminuição da angiogênese e pelo aumento da MRONJ no tecido ósseo, os bisfosfonatos possuem uma maior alteração no mecanismo ósseo.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências OdontológicasUFSMBrasilOdontologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessBisfosfonatosExodontiaDenosumabDisphosphonatesTooth extractionCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIAAvaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistarClinical and histological e evaluation of mandibular osteonecrosis induced by bone modifying agents in wistar ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisDanesi, Cristiane Cademartorihttp://lattes.cnpq.br/9106848911495258Ferrazzo, Kivia LinharesXXXXXXXXXXXXXXBarin, LuisaXXXXXXXXXXXXXXXMarinho, RobertoXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXSilva, Luisa Berlato400200000000600e4964e40-0663-4dd4-8f14-d62cdf602ede1dc44013-ec57-4497-9b49-ad389c38a33b04b974c8-cef0-437f-afa6-2a447a22eb9a12cdec15-31d1-4e31-89fb-32ab2a72c1ba019bd909-2c54-4eef-9485-76e2f1f9da0breponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCO_2021_SILVA_LUISA.pdfDIS_PPGCO_2021_SILVA_LUISA.pdfDissertação de Mestradoapplication/pdf14729909http://repositorio.ufsm.br/bitstream/1/21150/1/DIS_PPGCO_2021_SILVA_LUISA.pdfcf2933f252a2562debb7193d949e1d88MD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
dc.title.alternative.eng.fl_str_mv |
Clinical and histological e evaluation of mandibular osteonecrosis induced by bone modifying agents in wistar rats |
title |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
spellingShingle |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar Silva, Luisa Berlato Bisfosfonatos Exodontia Denosumab Disphosphonates Tooth extraction CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
title_full |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
title_fullStr |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
title_full_unstemmed |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
title_sort |
Avaliação clínica e histológica de osteonecrose mandibular induzida por agentes modificadores ósseos em ratos wistar |
author |
Silva, Luisa Berlato |
author_facet |
Silva, Luisa Berlato |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Danesi, Cristiane Cademartori |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9106848911495258 |
dc.contributor.advisor-co1.fl_str_mv |
Ferrazzo, Kivia Linhares |
dc.contributor.advisor-co1Lattes.fl_str_mv |
XXXXXXXXXXXXXX |
dc.contributor.referee1.fl_str_mv |
Barin, Luisa |
dc.contributor.referee1Lattes.fl_str_mv |
XXXXXXXXXXXXXXX |
dc.contributor.referee2.fl_str_mv |
Marinho, Roberto |
dc.contributor.referee2Lattes.fl_str_mv |
XXXXXXXXXXXXXX |
dc.contributor.authorLattes.fl_str_mv |
XXXXXXXXXXXXXXXXXXXXXX |
dc.contributor.author.fl_str_mv |
Silva, Luisa Berlato |
contributor_str_mv |
Danesi, Cristiane Cademartori Ferrazzo, Kivia Linhares Barin, Luisa Marinho, Roberto |
dc.subject.por.fl_str_mv |
Bisfosfonatos Exodontia Denosumab |
topic |
Bisfosfonatos Exodontia Denosumab Disphosphonates Tooth extraction CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
Disphosphonates Tooth extraction |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
Osteonecrosis is a bone pathology, with a still unknown etiopathogenesis, which was first reported in 2003 by Marx. In 2014 the Association of Oral and Maxillofacial Surgeons (AAOMS) described the concept of osteonecrosis, as an area of bone exposure in the jaw or jaw that does not repair in eight weeks due to a temporary or permanent loss of blood supply at the site. It affects, in most cases, patients who chronically use antiresorptive drugs and some associated factors such as corticosteroid therapy, diabetes mellitus, tooth extraction and other invasive dental procedures. Recent work investigates in rats the osteonecrosis induced by these drugs, such as alendronate (AL), zoledronic acid (Z) and denosumab (Dmab), in order to clarify the etiopathogenesis, as well as to study means of prevention and treatment of the disease. the aim of this study was to compare antiresorptive drugs in an animal model in MRONJ rats, using three different antiresorptive drugs: alendronate, zoledronic acid and denosumab, one for each experimental group, based on the clinical and histological parameters of the region undergoing extraction. The clinical parameters evaluated were: area of bone exposure, fistula, poor healing of soft tissue and inflammation in the alveolus. The histological parameters included the analysis of bone necrosis, inflammatory infiltrate (qualitative and quantitative analysis), blood vessels (quantitative analysis), bone sequestration and root rest. There were 35 male Wistar rats, randomized into 6 groups: Negative Control Group (CN) physiological saline therapy: GNZ (n = 6), GNAL (n = 6), GNDmab (n = 5); Alendronate Group (GAL) therapy with AL (n = 6); Zometa Group (GZ) Z therapy (n = 6); Denosumab Group (GDmab) Dmab therapy (n = 6). The dose applied to each animal will be according to its weekly weight, following the ratio: GAL 1 mg / Kg - subcutaneous, GZ 0.06mg / kgintraperitoneal and GDmab 0.25mg / kg - intraperitoneal. The GAL group was submitted to 8 applications of LA for a period of 8 weeks (1 weekly application), when completing the eighth week the rats were submitted to tooth extraction. And after 28 days of tooth extraction, they were euthanized, along with 6 rats from the GNAL group. The medication was maintained, once a week, until euthanasia (thirteenth week) for the GAL group. The GZ group received Z four times a week, for four weeks, when the fourth week was completed, tooth extraction was performed, after which the 28-day period was awaited for the euthanasia of the animals in the respective group and another 6 in the GNZ group. The GDmab group received a total of 8 applications of Dmab, for a period of 4 weeks (2 weekly applications), when the fourth week was completed, the animals in the group underwent dental extraction and after 28 days were euthanized, together with the 6 remaining rats from the GNDmab group. The statistical analysis for qualitative variables was used Fisher's exact test, and for the analysis of quantitative variables, One-way ANOVA with Tukey's post hoc was used. Considering a significance level of 0.05. Our results demonstrated a higher prevalence of histological osteonecrosis in the group in the BFs when compared to the Denosumab group, as well as the decrease in the number of vessels was more frequent in the groups of the BFs. Thus, we conclude that, due to the decrease in angiogenesis and the increase in MRONJ in bone tissue, bisphosphonates have a greater alteration in the bone mechan |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-06-18T17:31:47Z |
dc.date.available.fl_str_mv |
2021-06-18T17:31:47Z |
dc.date.issued.fl_str_mv |
2021-01-14 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21150 |
url |
http://repositorio.ufsm.br/handle/1/21150 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400200000000 |
dc.relation.confidence.fl_str_mv |
600 |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Odontológicas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Odontologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
bitstream.url.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
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1801223943633240064 |