Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients
Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients
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DOI：
10.4317/medoral.17150
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发表时间：
2011-11-01
影响因子：
2.2
通讯作者：
Korhan-Oral, Cuneyt
中科院分区：
文献类型：
--
作者：
Ali-Erdem, Mehmet;Burak-Cankaya, Abdulkadir;Korhan-Oral, Cuneyt
目的：本研究的目的是复制临床和组织学表现的双膦酸盐诱导的颌骨骨坏死（BONJ）的疾病状态的动物模型。在动物模型中成功再现BONJ样适应症将有助于研究BONJ的发病机制以及预防和治疗策略。材料与方法：80只大鼠前瞻性随机分为两组，对照组（40只）和研究组（40只）。研究组中的所有动物在第7、14或21天皮下注射1 mg/kg剂量的地塞米松（DX）;并在DX的最后一天皮下施用1、2或3个剂量的7.5 μ g/kg唑来膦酸（ZA）。在戊巴比妥诱导的全身麻醉下，每组一半动物拔除左下颌磨牙，其余动物拔除左上颌磨牙。所有动物在拔牙后二十八（28）天被安乐死。结果：在双膦酸盐-地塞米松（BP-DX）治疗的牙槽中，新骨小梁的量显著减少。发现两组之间的差异具有统计学显著性（p= 0.0001）。两组牙槽窝均无异物反应，纤维化程度无显著差异（p= 0.306）。BP-DX治疗的牙槽骨坏死评分显著更高（p= 0.015）。研究组的炎症评分明显高于对照组（p= 0，0001）。结论：本研究为BONK动物模型的建立提供了初步观察。但我们认为有必要进行其他研究，只有BP治疗组和更大的研究人群。
Aim: The aim of this study is to replicate both clinical and histological presentation of bisphosphonate induced osteonecrosis of the jaws (BONJ) in an animal model of the disease state. Successful recapitulation of a BONJ-like indication in an animal model will be useful for studying pathogenesis, as well as prevention and treatment strategies for BONJ.Materials and Methods: Eighty (80) rats were prospectively and randomly divided into two groups; control group(40) and study group(40). All animals in study group, injected with a dose of 1 mg/kg dexamethasone (DX) subcutaneously on day 7, 14, or 21; and 1, 2, or 3 doses of 7.5 mu g/kg zoledronic acid (ZA) subcutaneously administered to coincide with the last day of DX. Half of the animals from each group underwent extraction of the left mandibular molars and the remaining animals underwent extraction of the left maxillary molars under pentobarbital-induced general anesthesia. All animals were euthanized twenty-eight (28) days following tooth extractions.Results: The amount of new bone trabecules as significantly decreased in bisphosphonate-dexamethasone (BP-DX) treated sockets. Difference between both groups was found statistically significant (p=0,0001). There's no foreign body reaction in sockets of both groups and no significance difference observed for fibrosis (p=0,306). The necrosis scores were significantly higher in BP-DX treated sockets (p=0,015). The inflamation scores were significantly higher for study group (p=0,0001).Conclusion: This study provides preliminary observations for the development of an animal model of BONJ. But we think that there is need for other studies have only BP treated group and larger study population.