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唑来膦酸治疗大鼠的牙槽骨修复延迟和骨坏死:宏观、微观和分子分析。

Delayed alveolar bone repair and osteonecrosis associated with Zoledronic Acid therapy in rats: macroscopic, microscopic and molecular analysis.

机构信息

UniCesumar - Departamento de Odontologia, Maringá, PR, Brasil; Universidade de São Paulo, Faculdade de Odontologia de Bauru, Departamento de Cirurgia, Estomatologia, Patologia e Radiologia, Bauru, SP, Brasil.

Clínica Odontológica Privada.

出版信息

J Appl Oral Sci. 2020 Sep 25;28:e20200204. doi: 10.1590/1678-7757-2020-0204. eCollection 2020.

DOI:10.1590/1678-7757-2020-0204
PMID:32997086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7518245/
Abstract

OBJECTIVE

This study aims to evaluate bone repair and the development of the medication related osteonecrosis of the jaw (MRONJ) associated with the use of zoledronic acid in Wistar rats.

METHODOLOGY

48 male Wistar rats were divided into four groups: ZA, treated with intraperitoneal zoledronic acid, 0.6 mg/kg every 28 days, totaling five doses; control (C), treated with 0.9% sodium chloride; ZA-surgical (SZA) and C-surgical (SC), submitted to extraction of the right upper molars 45 days after the first application. Alveolar bone repair was evaluated by macroscopic and histological analysis. Protein expression evaluations were performed by qPCR.

RESULTS

Macroscopic evaluation showed that 91.66% (11) of the animals in the SZA group and 41.66% (5) from the SC group presented solution of epithelium continuity (P<0.05). All animals in the SZA group and none in the SC group had bone sequestration. The area of osteonecrosis was higher in the SZA group than in the SC group (P<0.05). In molecular evaluation, the SZA group presented changes in the expression of markers for osteoclasts, with increased RANK and RANKL, and a decrease in OPG.

CONCLUSION

The results highlighted strong and evident interference of zoledronic acid in bone repair of the socket, causing osteonecrosis and delayed bone remodeling.

摘要

目的

本研究旨在评估唑来膦酸在 Wistar 大鼠中的应用与药物相关性颌骨坏死(MRONJ)相关的骨修复和发展。

方法

48 只雄性 Wistar 大鼠分为四组:ZA 组,腹腔内给予唑来膦酸,每 28 天 0.6mg/kg,共 5 剂;对照组(C),给予 0.9%氯化钠;ZA 手术组(SZA)和 C 手术组(SC),在第一次给药后 45 天拔除右上磨牙。通过宏观和组织学分析评估牙槽骨修复情况。通过 qPCR 进行蛋白表达评估。

结果

宏观评估显示,SZA 组中有 91.66%(11)只动物和 SC 组中有 41.66%(5)只动物出现上皮连续性中断(P<0.05)。SZA 组所有动物均出现骨隔离,而 SC 组无一例出现。SZA 组的骨坏死面积大于 SC 组(P<0.05)。在分子评估中,SZA 组破骨细胞标志物的表达发生变化,RANK 和 RANKL 增加,而 OPG 减少。

结论

结果强调了唑来膦酸对牙槽骨修复的强烈和明显干扰,导致骨坏死和骨重塑延迟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/323ee661d15b/1678-7757-jaos-28-e20200204-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/1d0e154d9eb4/1678-7757-jaos-28-e20200204-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/70fe19fbc338/1678-7757-jaos-28-e20200204-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/bc52f6aff4d6/1678-7757-jaos-28-e20200204-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/85dc5797670d/1678-7757-jaos-28-e20200204-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/e629516e99c8/1678-7757-jaos-28-e20200204-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/517a969eed5d/1678-7757-jaos-28-e20200204-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/323ee661d15b/1678-7757-jaos-28-e20200204-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/1d0e154d9eb4/1678-7757-jaos-28-e20200204-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/70fe19fbc338/1678-7757-jaos-28-e20200204-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/bc52f6aff4d6/1678-7757-jaos-28-e20200204-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/85dc5797670d/1678-7757-jaos-28-e20200204-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/e629516e99c8/1678-7757-jaos-28-e20200204-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/517a969eed5d/1678-7757-jaos-28-e20200204-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed7/7518245/323ee661d15b/1678-7757-jaos-28-e20200204-gf07.jpg

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