Development of a Preclinical Double Model of Mandibular Irradiated Bone and Osteoradionecrosis in New Zealand Rabbits.

IF 2.3 3区 医学 Q1 OTORHINOLARYNGOLOGY
Alessandra Ruaro, Stefano Taboni, Harley H L Chan, Tiziana Mondello, Patricia Lindsay, Teesha Komal, Lara Alessandrini, Marta Sbaraglia, Elena Bellan, Roberto Maroldi, Jason Townson, Michael J Daly, Federica Re, Chiara Pasini, Marco Krengli, Luciana Sartore, Domenico Russo, Piero Nicolai, Marco Ferrari, Ralph W Gilbert, Jonathan C Irish
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Abstract

Purpose: Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches.

Methods: Nine New Zealand white rabbits were irradiated using a single beam positioned to the left of the mandible and directed perpendicular to the left mandible. A 10 × 10 mm2 region of interest (ROI) located below the first molar tooth on the left side was identified and irradiated with 7 Gy each fraction, once every 2 days, for five fractions. Dose distributions demonstrated that the corresponding ROI on the contralateral (right) mandibular side received approximately 5 Gy each fraction, thus bilateral irradiation of the mandible was achieved. ROIs were categorized as ROIH on the left side receiving the high dose and ROIL on the right side receiving the low dose. Rabbits were followed up clinically and imaged monthly. After 4 months, the irradiated bone was excised, and histological examination of ROIs was performed.

Results: Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROIH, which consisted of cortical erosion and loss of trabeculae. ROIL did not show any radiological evidence of bone damage. Histologically, both sides showed comparable signs of injury, with marked reduction in osteocyte count and increase in empty lacunae count.

Conclusions: A preclinical double model was successfully developed. The side receiving the higher dose showed radiological and histological signs of bone damage, resulting in an ORN model. Whereas the contralateral side, receiving the lower dose, presented with histological damage only and a normal radiological appearance. This work describes the creation of a double model, an ORN and irradiated bone model, for further study using this animal species.

新西兰兔下颌骨辐照和骨坏死临床前双重模型的开发
目的:放疗(RT)在头颈部癌症治疗中起着至关重要的作用。然而,放疗可能导致严重的、具有挑战性的不良反应,如骨坏死(ORN)。本文提出了一种辐照骨和ORN的临床前兔子模型,旨在开发一种可行的模型,用于研究新的治疗方法:方法:使用位于下颌骨左侧并垂直于左下颌骨的单光束对九只新西兰白兔进行照射。确定位于左侧第一臼齿下方的 10 × 10 平方毫米感兴趣区(ROI),每隔 2 天照射一次,每次 7 Gy,共照射 5 次。剂量分布显示,下颌骨对侧(右侧)的相应 ROI 每部分接受了约 5 Gy 的照射,因此实现了下颌骨的双侧照射。左侧接受高剂量的 ROIH 和右侧接受低剂量的 ROIL 被归类为 ROI。每月对兔子进行临床随访和成像。4 个月后,切除受照射的骨骼,并对 ROIs 进行组织学检查:结果:ROIH照射16周后,所有兔子(100%)都发现了提示ORN的放射学症状,包括皮质侵蚀和骨小梁缺失。ROIL 未显示任何骨损伤的放射学证据。从组织学角度看,两侧均显示出相似的损伤迹象,骨细胞数量明显减少,空洞数量增加:结论:成功建立了临床前双重模型。结论:临床前双模型的建立是成功的。接受较高剂量的一侧显示出骨损伤的放射学和组织学迹象,从而形成 ORN 模型。而接受较低剂量的一侧仅出现组织学损伤,放射学外观正常。这项工作描述了如何创建一个双重模型,即 ORN 和辐照骨模型,以便利用这种动物物种进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.00
自引率
6.90%
发文量
278
审稿时长
1.6 months
期刊介绍: Head & Neck is an international multidisciplinary publication of original contributions concerning the diagnosis and management of diseases of the head and neck. This area involves the overlapping interests and expertise of several surgical and medical specialties, including general surgery, neurosurgery, otolaryngology, plastic surgery, oral surgery, dermatology, ophthalmology, pathology, radiotherapy, medical oncology, and the corresponding basic sciences.
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