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双膦酸盐治疗的大鼠拔牙窝愈合:多发性骨髓瘤患者颌骨骨坏死相关双膦酸盐的动物模型。

Extraction socket healing in rats treated with bisphosphonate: animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients.

机构信息

Istanbul University, Department of Oral & Maxillofacial Surgery, 34093 Çapa-Fatih, Istanbul Turkey.

出版信息

Med Oral Patol Oral Cir Bucal. 2011 Nov 1;16(7):e879-83. doi: 10.4317/medoral.17150.

DOI:10.4317/medoral.17150
PMID:21743422
Abstract

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 µg/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.

摘要

目的

本研究旨在复制双膦酸盐诱导的下颌骨骨坏死(BONJ)的临床和组织学表现,建立疾病状态的动物模型。在动物模型中成功重现类似 BONJ 的表现,将有助于研究发病机制以及预防和治疗 BONJ 的策略。

材料和方法

80 只大鼠前瞻性随机分为两组;对照组(40 只)和研究组(40 只)。研究组所有动物在第 7、14 或 21 天皮下注射 1mg/kg 地塞米松(DX),第 7 天、第 14 天或第 21 天皮下注射 1、2 或 3 次 7.5μg/kg 唑来膦酸(ZA),与 DX 的最后一天同时给药。每组各有一半动物在戊巴比妥钠全麻下拔除左侧下颌磨牙,其余动物拔除左侧上颌磨牙。所有动物在拔牙后 28 天处死。

结果

双膦酸盐-地塞米松(BP-DX)治疗的拔牙窝中新生骨小梁数量明显减少。两组间差异有统计学意义(p=0.0001)。两组拔牙窝均无异物反应,纤维化无显著差异(p=0.306)。BP-DX 治疗的拔牙窝坏死评分明显升高(p=0.015)。研究组炎症评分明显升高(p=0.0001)。

结论

本研究为 BONJ 动物模型的发展提供了初步观察结果。但我们认为,需要对仅接受 BP 治疗的组和更大的研究人群进行其他研究。

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