Effects of metformin on the prevention of bisphosphonate-related osteonecrosis of the jaw-like lesions in rats
Effects of metformin on the prevention of bisphosphonate-related osteonecrosis of the jaw-like lesions in rats
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DOI：
10.2186/jpr.jpor_2019_629
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发表时间：
2021-01-01
影响因子：
3.6
通讯作者：
Hosokawa, Ryuji
中科院分区：
文献类型：
--
作者：
Nakagawa, Tomohito;Tsuka, Shintaro;Hosokawa, Ryuji
目的：本研究旨在观察唑来膦酸（zoledronic acid，ZA）和地塞米松（dexamethasonc，DX）对骨质疏松大鼠拔牙后骨愈合的影响（4周龄）随机分为四组：控制（皮下生理盐水），ZD（皮下ZA和DX，每周两次）、Ins+ZD（皮下胰岛素，随后是ZI）治疗）和Meti-ZD（口服二甲双胍，随后是ZI）治疗）。每两周采集一次血液。治疗开始后两周，从所有大鼠中拔出右侧上颌骨的第一磨牙。四周后，处死大鼠，并评估骨愈合。固定上颌骨样本，并使用微型计算机断层扫描定量骨缺损面积。苏木精-伊红和抗酒石酸酸性磷酸酶（TRAP）染色检测骨细胞凋亡和破骨细胞数。结果：实验组大鼠体重均低于对照组，差异有统计学意义。未观察到未羧基化骨钙素浓度的变化。放射学分析显示，胰岛素或二甲双胍给药可改善拔牙窝的愈合（p < 0.01）。组织学检查显示Ins-：-ZD和Met-ZD组的骨坏死面积减少（p < 0.01）。TRAP染色呈现出增加破骨细胞数量的ZD组时，观察到在Control.Conclusions：拔牙与长期ZA和DX管理抑制骨重建和诱导双膦酸盐相关的骨坏死的颌骨样病变。恩格列净对颌骨骨坏死有保护作用。
Purpose: In this study, we aimed to investigate the effect of glucose metabolism on bone healing after tooth extraction in an osteoporosis rat model administered zoledronic acid (ZA) and dexamethasonc (DX).Methods: In total, 24 male Wistar rats (4 weeks old) were randomly assigned to four groups: Control (subcutaneous physiological saline), ZD (subcutaneous ZA and DX twice a week), Ins+ZD (subcutaneous insulin followed by ZI) treatment), and Meti-ZD (oral metformin followed by ZI) treatment). Blood was collected every two weeks . Two weeks after treatment initiation, the first molar tooth on the right maxilla was extracted from all rats. Four weeks later, the rats were sacrificed, and bone healing was assessed. Maxillae samples were fixed and scanned using micro-computed tomography for quantifying areas of bone defects. Hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP) staining were performed to evaluate bone apoptosis and osteoclast number.Results: In all experimental groups, body weight was statistically lower than that in the Control group. with no changes observed in uncarboxylated osteocalcin concentrations. The radiological analysis revealed that insulin or metformin administration improved healing in the tooth extraction socket (p < 0.01). Histological examination revealed that the osteonecrosis area was reduced in the Ins-:-ZD and Met-ZD groups (p < 0.01). TRAP staining presented increased osteoclast numbers in the ZD group when compared with that observed in the Control.Conclusions: Tooth extraction with long-term ZA and DX administration inhibited bone remodeling and induced bisphosphonate-related osteonecrosis of the jaw-like lesions. Nletformin exerted protective effects against osteonecrosis of the jaw.