Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: A novel ONJ mouse model

dc.contributorUniv Calif Los Angeles
dc.contributorUniversidade Estadual Paulista (Unesp)
dc.contributorUniv So Calif
dc.creatorMolon, Rafael Scaf de [UNESP]
dc.creatorCheong, Simon
dc.creatorBezouglaia, Olga
dc.creatorDry, Sarah M.
dc.creatorPirih, Flavia
dc.creatorCirelli, Joni Augusto [UNESP]
dc.creatorAghaloo, Tara L.
dc.creatorTetradis, Sotirios
dc.date2015-03-18T15:53:21Z
dc.date2015-03-18T15:53:21Z
dc.date2014-11-01
dc.date.accessioned2023-09-09T11:05:02Z
dc.date.available2023-09-09T11:05:02Z
dc.identifierhttp://dx.doi.org/10.1016/j.bone.2014.07.027
dc.identifierBone. New York: Elsevier Science Inc, v. 68, p. 11-19, 2014.
dc.identifier8756-3282
dc.identifierhttp://hdl.handle.net/11449/116458
dc.identifier10.1016/j.bone.2014.07.027
dc.identifierWOS:000343195100003
dc.identifier2628593693450121
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8765943
dc.descriptionAlthough osteonecrosis of the jaws (ONJ), a serious complication of antiresorptive medications, was reported a decade ago, the exact mechanisms of disease pathophysiology remain elusive. ONJ-like lesions can be induced in animals after antiresorptive treatment and experimental interventions such as tooth extraction or periapical or periodontal disease. However, experimental induction and manipulation of disease progression does not always reflect clinical reality. Interestingly, naturally occurring maxillofacial abscesses, inducing aggressive inflammation of the peri-radicular mucosa with significant osteolysis and alveolar bone expansion, have been reported in mice. Here, we aimed to explore whether osteonecrotic lesions would develop in areas of maxillary peri-radicular infections, in mice on antiresorptive medications with distinct pharmacologic action, thus establishing a novel ONJ animal model. Mice were treated with RANK-Pc or OPG-Fc that bind to RANKL or with the potent bisphosphonate zoledronic acid (ZA). Maxillae were assessed radiographically and histologically. mu CT imaging of vehicle mice revealed several maxillae with altered alveolar bone morphology, significant ridge expansion and large lyric areas. However, in RANK-Fc, OPG-Fc and ZA treated animals the extent of bone loss was significantly less, but exuberant bone deposition was noted at the ridge periphery. BV and BV/TV were increased in the diseased site of antiresorptive vs. veh animals. Histologically, extensive inflammation, bone resorption and marginal gingival epithelium migration were seen in the diseased site of vehicle animals. RankFc, OPG-Fc and ZA reduced alveolar bone loss, increased periosteal bone formation, and induced areas of osteonecrosis, and bone exposure that in many animals covered significant part of the alveolar bone. Collectively, our data demonstrate ONJ-like lesions at sites of maxillary peri-radicular infection, indistinguishable in mice treated with RAKL inhibitors vs. zoledronate. This novel mouse model of spontaneous. ONJ supports a central role of osteoclast inhibition and infection/inflammation in ONJ pathogenesis and validates and complements existing animal models employing experimental interventions. (C) 2014 Elsevier Inc. All rights reserved.
dc.descriptionAmgen Inc.
dc.descriptionNIH/NIDCR
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordination for the Improvement of Higher Level -or Education-Personnel
dc.descriptionUniv Calif Los Angeles, Sch Dent, Div Diagnost & Surg Sci, Los Angeles, CA 90095 USA
dc.descriptionSao Paulo State Univ, Sch Dent Araraquara, Dept Diag & Surg, BR-14801903 Araraquara, Brazil
dc.descriptionUniv So Calif, Ostrow Sch Dent, Los Angeles, CA USA
dc.descriptionUniv Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
dc.descriptionUniv Calif Los Angeles, Sch Dent, Div Associated Specialties, Los Angeles, CA 90095 USA
dc.descriptionUniv Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
dc.descriptionSao Paulo State Univ, Sch Dent Araraquara, Dept Diag & Surg, BR-14801903 Araraquara, Brazil
dc.descriptionNIH/NIDCRDE019465
dc.descriptionFAPESP: 12/09968-5
dc.descriptionCoordination for the Improvement of Higher Level -or Education-Personnel11575/13-1
dc.format11-19
dc.languageeng
dc.publisherElsevier B.V.
dc.relationBone
dc.relation4.455
dc.relation1,652
dc.rightsAcesso restrito
dc.sourceWeb of Science
dc.subjectOsteonecrosis of the jaw
dc.subjectONJ
dc.subjectAntiresorptives
dc.subjectBisphosphonates
dc.subjectAlveolar bone
dc.subjectOsteoclasts
dc.titleSpontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: A novel ONJ mouse model
dc.typeArtigo


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