A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw
A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw
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DOI：
10.1111/j.1600-0714.2009.00878.x
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发表时间：
2010-05-01
影响因子：
3.3
通讯作者：
Di Lenarda, Roberto
中科院分区：
文献类型：
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作者：
Biasotto, Matteo;Chiandussi, Silvia;Di Lenarda, Roberto
本研究的目的是评估一种新的双膦酸盐相关骨坏死动物模型，该模型真实地再现了相同的病理人类状况。5只Wistar大鼠静脉注射唑来膦酸0.04 mg，每周1次，共5周。2周后，动物拔除上臼齿，在同一部位产生直径为4 mm的骨缺损。拔牙7周后，对动物进行临床检查，并进行骨密度成像。再过一周后，处死大鼠，进行计算机断层扫描和组织学分析。5只未接受唑来膦酸治疗并接受相同手术治疗的大鼠用作对照。在拔牙后7周，所有用唑来膦酸治疗的大鼠显示出缺损扩大和骨暴露。这些特征得到了骨密度图的证实。对照组大鼠在扫描过程中显示骨缺损的上皮化和造影剂的正常摄取。计算机断层扫描显示皮质边缘不规则和骨质破坏，而对照组不明显。在显微镜下，样品显示坏死的骨，骨细胞的损失和周边吸收没有炎症浸润，而对照组显示正常的骨愈合。用唑来膦酸治疗的大鼠可以被认为是一种新的、可靠的和可重复的动物模型，以更好地理解颌骨骨坏死的病理生理学并开发治疗方法。
The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach.