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

Autor(es)

Biguetti, Claudia Cristina ^[1] ; De Oliva, Andre Prime Hergesel ^[1] ; Healy, Kent ^[2] ; Mahmoud, Ramez Hassan ^[1] ; Custodio, Isabela Do Carmo ^[3] ; Constantino, Dulce Helena ^[3] ; Ervolino, Edilson ^[1] ; Hungaro Duarte, Marco Antonio ^[4] ; Fakhouri, Walid D. ^[2] ; Matsumoto, Mariza Akemi ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Dent, Dept Basic Sci, Aracatuba, SP - Brazil

^[2] Univ Texas Hlth Sci Ctr Houston, Dept Diagnost & Biomed Sci, Houston, TX 77030 - USA

^[3] Univ Sagrado Coracao, Dept Hlth Sci, Bauru, SP - Brazil

^[4] Univ Sao Paulo, FOB USP, Dept Endodont, Bauru, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 14, n. 6 JUN 14 2019.
• Citações Web of Science: 0

Resumo

Treatment 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 250 mu g/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. (AU)

• Processo FAPESP: 13/04714-8 - Efeito do chá verde no processo de reparo alveolar de ratos tratados com bifosfonato
• Beneficiário: Mariza Akemi Matsumoto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/19409-0 - Reparo ósseo pós exodontia em camundongos fêmeas senis 129/SV- WT e 129/Sv 5LOKO tratadas com bifosfonato de alta potência
• Beneficiário: Isabela do Carmo Custodio
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 19/10355-7 - Osteonecrose dos maxilares relacionada à medicamentos após extração dentária em camundongos fêmeas senescentes tratadas com ácido zoledrônico: caracterização histológica e imunoistoquímica
• Beneficiário: Mariza Akemi Matsumoto
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo