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
{"title":"Development of a Preclinical Double Model of Mandibular Irradiated Bone and Osteoradionecrosis in New Zealand Rabbits.","authors":"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","doi":"10.1002/hed.27955","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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 mm<sup>2</sup> 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 ROI<sub>H</sub> on the left side receiving the high dose and ROI<sub>L</sub> 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.</p><p><strong>Results: </strong>Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROI<sub>H</sub>, which consisted of cortical erosion and loss of trabeculae. ROI<sub>L</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/hed.27955","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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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