Medication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: Microtomographic, histological and immunohistochemical characterization

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dc.contributor.authorBiguetti, Claudia Cristina [UNESP]
dc.contributor.authorDe Oliva, André Hergesel [UNESP]
dc.contributor.authorHealy, Kent
dc.contributor.authorMahmoud, Ramez Hassan [UNESP]
dc.contributor.authorCustódio, Isabela Do Carmo
dc.contributor.authorConstantino, Dulce Helena
dc.contributor.authorErvolino, Edilson [UNESP]
dc.contributor.authorDuarte, Marco Antonio Hungaro
dc.contributor.authorFakhouri, Walid D.
dc.contributor.authorMatsumoto, Mariza Akemi [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversity of Texas Health Science Center at Houston
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2019-10-06T17:12:20Z
dc.date.available2019-10-06T17:12:20Z
dc.date.issued2019-06-01
dc.description.abstractTreatment with cumulative dosages of zoledronic acid (ZA) in elderly patients is a risk factor for the development of medication-related osteonecrosis of the jaws (MRONJ), mainly related to surgical triggers such as tooth extraction. However, animal models for the investigation and understanding of MRONJ pathophysiology in senescent and postmenopausal stages remains to be developed and characterized. The aim of this study was to analyze MRONJ development in senescent female mice treated with cumulative dosages of ZA. For this purpose, twenty 129/Sv female mice, 64 weeks old, were treated with 0.9% saline solution as control group (n = 10), and with ZA at 250μg/Kg (n = 10), once a week, starting 4 weeks before the upper right incisor extraction and until the end of the experimental time points (7 days and 21 days). At 7 and 21 days post-surgery, specimens were harvested for microCT, histological, birefringence and immunohistochemical analysis. Clinically, an incomplete epithelialization was observed in ZA group at 7 days and a delayed bone matrix mineralization and collagen maturation at 7 and 21 days compared to the controls. Controls revealed sockets filled with mature bone at 21 days as observed by microCT and birefringence, while ZA group presented delayed bone deposition at 7 and 21 days, as well increased leukocyte infiltration and blood clot at 7 days, and increased bone sequestrum and empty osteocyte lacunae at 21 days (p<0.05). Also, ZA group presented decreased quantity of TGFb+ and Runx-2+ cells at 7 days, and decreased quantity of TRAP+ osteoclasts compared to the control at 21 days (p<0.05). Altogether, these data demonstrate the usefulness of this model to understanding the pathophysiology of MRONJ.en
dc.description.affiliationDepartment of Basic Sciences São Paulo State University (UNESP) School of Dentistry
dc.description.affiliationDepartment of Diagnostic and Biomedical Sciences University of Texas Health Science Center at Houston
dc.description.affiliationDepartment of Health Sciences Universidade Sagrado Coracção - USC
dc.description.affiliationDepartment of Endodontics São Paulo University - FOB/USP
dc.description.affiliationUnespDepartment of Basic Sciences São Paulo State University (UNESP) School of Dentistry
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0214173
dc.identifier.citationPLoS ONE, v. 14, n. 6, 2019.
dc.identifier.doi10.1371/journal.pone.0214173
dc.identifier.issn1932-6203
dc.identifier.lattes4408095517346846
dc.identifier.lattes8621510886887389
dc.identifier.orcid0000-0003-4859-0583
dc.identifier.scopus2-s2.0-85067465195
dc.identifier.urihttp://hdl.handle.net/11449/190411
dc.language.isoeng
dc.relation.ispartofPLoS ONE
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.titleMedication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: Microtomographic, histological and immunohistochemical characterizationen
dc.typeArtigo
unesp.author.lattes4408095517346846[7]
unesp.author.lattes8621510886887389
unesp.author.orcid0000-0003-4859-0583[7]

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