Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | http://tede2.pucrs.br/tede2/handle/tede/9984 |
Resumo: | Osteoporosis is a silent disorder that affects a great number of people worldwide, and is characterized by loss of bone mass and architectural deterioration of bone, which increases the risk of fractures. This condition requires medical treatment, where bisphosphonates are the most used antiresorptive drugs. Medication-related osteonecrosis of the jaw (MRONJ) is an adverse effect of antiresorptive therapy and, even though the literature associates this disorder with bisphosphonates and denosumab, it is not known if other antiresorptive drugs would also be involved. This study aimed to analyze macro- and microscopic features of tooth extraction sites in rats undergoing sodium alendronate, raloxifene or strontium ranelate therapies. Forty eight Wistar rats were allocated into four groups according to the treatment: (1) alendronate, (2) raloxifene, (3) strontium ranelate and (4) control. All animals underwent tooth extraction of the upper right molars at the 60th day of treatment. At the 90th day, the animals were euthanized and the maxillae were dissected for macroscopic analysis and histomorphometry with hematoxylin and eosin (H&E); immunohistochemistry with RANKL and OPG; and scanning electron microscopy analysis (SEM). Macroscopic examination showed greater frequency and syze of mucosal lesion in the alendronate group. On H&E analysis, the proportion of non-vital bone was greater in the alendronate and strontium ranelate groups. Alendronate also showed more biofilm than raloxifene and strontium groups, higher inflammatory infiltrate than all the other groups and less vital bone than the control. The alendronate group had lower expression of RANKL and OPG, while the strontium ranelate group had lower levels of OPG than the other groups. On SEM analysis, the alendronate group showed a considerable number of microcracks on the alveolar bone surface, and few Howship lacunae and lack of bone cells as well. The raloxifen, strontium ranelate and control groups showed a large number of bone cells and Howship lacunae on the bone surface and few microcracks. Conclusion: Sodium alendronate determines, in tooth extraction sites, greater histologic and structural features compatible with MRONJ and reduced bone metabolism as well. Strontium ranelate is associated with non-vital bone, whereas raloxifen is not associated with MRONJ features. |
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Cherubini, Karenhttp://lattes.cnpq.br/8554444599739699http://lattes.cnpq.br/8400940212908621Koth, Valesca Sander2021-11-30T19:14:00Z2020-03-04http://tede2.pucrs.br/tede2/handle/tede/9984Osteoporosis is a silent disorder that affects a great number of people worldwide, and is characterized by loss of bone mass and architectural deterioration of bone, which increases the risk of fractures. This condition requires medical treatment, where bisphosphonates are the most used antiresorptive drugs. Medication-related osteonecrosis of the jaw (MRONJ) is an adverse effect of antiresorptive therapy and, even though the literature associates this disorder with bisphosphonates and denosumab, it is not known if other antiresorptive drugs would also be involved. This study aimed to analyze macro- and microscopic features of tooth extraction sites in rats undergoing sodium alendronate, raloxifene or strontium ranelate therapies. Forty eight Wistar rats were allocated into four groups according to the treatment: (1) alendronate, (2) raloxifene, (3) strontium ranelate and (4) control. All animals underwent tooth extraction of the upper right molars at the 60th day of treatment. At the 90th day, the animals were euthanized and the maxillae were dissected for macroscopic analysis and histomorphometry with hematoxylin and eosin (H&E); immunohistochemistry with RANKL and OPG; and scanning electron microscopy analysis (SEM). Macroscopic examination showed greater frequency and syze of mucosal lesion in the alendronate group. On H&E analysis, the proportion of non-vital bone was greater in the alendronate and strontium ranelate groups. Alendronate also showed more biofilm than raloxifene and strontium groups, higher inflammatory infiltrate than all the other groups and less vital bone than the control. The alendronate group had lower expression of RANKL and OPG, while the strontium ranelate group had lower levels of OPG than the other groups. On SEM analysis, the alendronate group showed a considerable number of microcracks on the alveolar bone surface, and few Howship lacunae and lack of bone cells as well. The raloxifen, strontium ranelate and control groups showed a large number of bone cells and Howship lacunae on the bone surface and few microcracks. Conclusion: Sodium alendronate determines, in tooth extraction sites, greater histologic and structural features compatible with MRONJ and reduced bone metabolism as well. Strontium ranelate is associated with non-vital bone, whereas raloxifen is not associated with MRONJ features.A osteoporose é uma doença silenciosa que afeta importante parcela da população mundial e caracteriza-se pela perda de massa óssea e deterioração da arquitetura do osso, com aumento do risco de fraturas. A condição requer tratamento medicamentoso, sendo os bisfosfonatos os fármacos antirreabsortivos mais empregados. A osteonecrose maxilar associada a medicamentos (MRONJ) constitui efeito adverso da terapia antirreabsortiva e, embora a literatura tenha associado essa condição ao uso de bisfosfonatos e denosumabe, ainda não foi esclarecido se outros fármacos antirreabsortivos estariam a ela associados. O presente trabalho teve por objetivo avaliar, macro e microscopicamente, sítios de exodontia em ratos tratados com alendronato de sódio, raloxifeno e ranelato de estrôncio. Quarenta e oito ratos Wistar foram alocados em quatro grupos, de acordo com o tratamento dispensado: (1) alendronato, (2) raloxifeno, (3) ranelato de estrôncio e (4) controle. Aos 60 dias de experimento, todos os animais foram submetidos a exodontias dos molares superiores do lado direito. A eutanásia foi realizada aos 90 dias, e as maxilas foram dissecadas para posterior análise macroscópica, histomorfométrica com hematoxilina e eosina (H&E) e imunoistoquímica (RANKL e OPG), bem como por microscopia eletrônica de varredura (MEV). À macroscopia, o grupo alendronato exibiu maior frequência e tamanho de lesão da mucosa oral. A análise em H&E exibiu proporção de osso não vital maior nos grupos alendronato e ranelato de estrôncio. O grupo alendronato ainda exibiu maior ocorrência de biofilme do que os grupos raloxifeno e ranelato de estrôncio, maior infiltrado inflamatório do que os demais grupos e menor ocorrência de osso vital do que o controle. O grupo alendronato teve menor expressão de RANKL e OPG, e o grupo ranelato de estrôncio menor expressão de OPG que os demais grupos. Na análise por MEV, o grupo alendronato exibiu superfície óssea com maior acúmulo de microfraturas e menor número de lacunas de Howship e elementos celulares. Significativa quantidade de elementos celulares foi observada na superfície óssea dos grupos controle, raloxifeno e ranelato de estrôncio. Conclusão: O alendronato de sódio determina, em sítios de exodontias, maior intensidade de alterações histológicas e estruturais associadas à MRONJ, bem como sinais de redução do metabolismo ósseo. O ranelato de estrôncio está associado com osso não vital, enquanto o raloxifeno não tem associação com alterações sugestivas de MRONJ.Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2021-11-29T20:10:33Z No. of bitstreams: 1 VALESCA_SANDER_KOTH_TES.pdf: 4059185 bytes, checksum: 3fed28ca0caa6088dfc1935b5c1cb104 (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2021-11-30T19:06:16Z (GMT) No. of bitstreams: 1 VALESCA_SANDER_KOTH_TES.pdf: 4059185 bytes, checksum: 3fed28ca0caa6088dfc1935b5c1cb104 (MD5)Made available in DSpace on 2021-11-30T19:14:00Z (GMT). No. of bitstreams: 1 VALESCA_SANDER_KOTH_TES.pdf: 4059185 bytes, checksum: 3fed28ca0caa6088dfc1935b5c1cb104 (MD5) Previous issue date: 2020-03-04Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/182739/TES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em OdontologiaPUCRSBrasilEscola de Ciências da Saúde da VidaOsteonecrose Associada a BisfosfonatosOsteoporoseCirurgia BucalMicroscopia EletrônicaBisphosphonate Related Osteonecrosis of the JawsOsteoporosisOral SurgeryElectron Scanning MicroscopyCIENCIAS DA SAUDE::ODONTOLOGIAAnálise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho será publicado como artigo ou livro60 meses30/11/2026-7411869720500764667500500600-20704984698792443491802873727776104890info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILTES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.jpgTES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.jpgimage/jpeg4096http://tede2.pucrs.br/tede2/bitstream/tede/9984/4/TES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.jpg9b0d64ac488a54f0e6b1f05e65fd65e3MD54TEXTTES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.txtTES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.txttext/plain1288http://tede2.pucrs.br/tede2/bitstream/tede/9984/3/TES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf.txt3782621e121d8aaa3accf70b3b7e7271MD53ORIGINALTES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdfTES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdfapplication/pdf593190http://tede2.pucrs.br/tede2/bitstream/tede/9984/2/TES_VALESCA_SANDER_KOTH_CONFIDENCIAL.pdf85ec7ddcf6c825b59a6f989be0f19ccaMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590http://tede2.pucrs.br/tede2/bitstream/tede/9984/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/99842021-11-30 20:00:26.248oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2021-11-30T22:00:26Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
title |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
spellingShingle |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo Koth, Valesca Sander Osteonecrose Associada a Bisfosfonatos Osteoporose Cirurgia Bucal Microscopia Eletrônica Bisphosphonate Related Osteonecrosis of the Jaws Osteoporosis Oral Surgery Electron Scanning Microscopy CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
title_full |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
title_fullStr |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
title_full_unstemmed |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
title_sort |
Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo |
author |
Koth, Valesca Sander |
author_facet |
Koth, Valesca Sander |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cherubini, Karen |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8554444599739699 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8400940212908621 |
dc.contributor.author.fl_str_mv |
Koth, Valesca Sander |
contributor_str_mv |
Cherubini, Karen |
dc.subject.por.fl_str_mv |
Osteonecrose Associada a Bisfosfonatos Osteoporose Cirurgia Bucal Microscopia Eletrônica |
topic |
Osteonecrose Associada a Bisfosfonatos Osteoporose Cirurgia Bucal Microscopia Eletrônica Bisphosphonate Related Osteonecrosis of the Jaws Osteoporosis Oral Surgery Electron Scanning Microscopy CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
Bisphosphonate Related Osteonecrosis of the Jaws Osteoporosis Oral Surgery Electron Scanning Microscopy |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
Osteoporosis is a silent disorder that affects a great number of people worldwide, and is characterized by loss of bone mass and architectural deterioration of bone, which increases the risk of fractures. This condition requires medical treatment, where bisphosphonates are the most used antiresorptive drugs. Medication-related osteonecrosis of the jaw (MRONJ) is an adverse effect of antiresorptive therapy and, even though the literature associates this disorder with bisphosphonates and denosumab, it is not known if other antiresorptive drugs would also be involved. This study aimed to analyze macro- and microscopic features of tooth extraction sites in rats undergoing sodium alendronate, raloxifene or strontium ranelate therapies. Forty eight Wistar rats were allocated into four groups according to the treatment: (1) alendronate, (2) raloxifene, (3) strontium ranelate and (4) control. All animals underwent tooth extraction of the upper right molars at the 60th day of treatment. At the 90th day, the animals were euthanized and the maxillae were dissected for macroscopic analysis and histomorphometry with hematoxylin and eosin (H&E); immunohistochemistry with RANKL and OPG; and scanning electron microscopy analysis (SEM). Macroscopic examination showed greater frequency and syze of mucosal lesion in the alendronate group. On H&E analysis, the proportion of non-vital bone was greater in the alendronate and strontium ranelate groups. Alendronate also showed more biofilm than raloxifene and strontium groups, higher inflammatory infiltrate than all the other groups and less vital bone than the control. The alendronate group had lower expression of RANKL and OPG, while the strontium ranelate group had lower levels of OPG than the other groups. On SEM analysis, the alendronate group showed a considerable number of microcracks on the alveolar bone surface, and few Howship lacunae and lack of bone cells as well. The raloxifen, strontium ranelate and control groups showed a large number of bone cells and Howship lacunae on the bone surface and few microcracks. Conclusion: Sodium alendronate determines, in tooth extraction sites, greater histologic and structural features compatible with MRONJ and reduced bone metabolism as well. Strontium ranelate is associated with non-vital bone, whereas raloxifen is not associated with MRONJ features. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-03-04 |
dc.date.accessioned.fl_str_mv |
2021-11-30T19:14:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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http://tede2.pucrs.br/tede2/handle/tede/9984 |
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http://tede2.pucrs.br/tede2/handle/tede/9984 |
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por |
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por |
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500 500 600 |
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1802873727776104890 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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Programa de Pós-Graduação em Odontologia |
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PUCRS |
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Brasil |
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Escola de Ciências da Saúde da Vida |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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