Michel Guillaume, Blery Pauline, Pilet Paul, Guicheux Jérôme, Weiss Pierre, Malard Olivier, Espitalier Florent
Service d'O.R.L. et de chirurgie cervico-faciale, Centre Hospitalier Universitaire de Nantes, CHU Hôtel Dieu, 1, Place A. Ricordeau, BP 1005, 44093, Nantes Cedex 01, France,
Calcif Tissue Int. 2015 Jul;97(1):62-8. doi: 10.1007/s00223-015-0010-9. Epub 2015 May 8.
Treatment of carcinomas of the upper aerodigestive tract often requires external radiation therapy. However, radiation affects all the components of bone, with different degrees of sensitivity, and may produce severe side effects such as mandibular osteoradionecrosis (ORN). Intraosseous vascularization is thought to be decreased after irradiation, but its impact on total bone volume is still controversial. The aim of this study was to compare intraosseous vascularization, cortical bone thickness, and total bone volume in a rat model of ORN versus nonirradiated rats, using a micro-computed tomography (micro-CT) analysis after intracardiac injection of a contrast agent. The study was performed on 8-week-old Lewis 1A rats (n = 14). Eleven rats underwent external irradiation on the hind limbs by a single 80-Gy dose. Three rats did not receive irradiation and served as controls for statistical analysis. Eight weeks after the external irradiation, all the animals received a barium sulfate intracardiac injection under general anesthesia. All samples were analyzed with the micro-computed tomography system at a resolution of 5.5 μm. The images were later processed to create 3D reconstructions and study vascularization, bone volume, and cortical thickness. Data from irradiated and nonirradiated rats were compared using the Kruskal-Wallis test. No animal died after irradiation. Nineteen irradiated tibias and six nonirradiated tibias were included for micro-CT analysis. The vessel percentage was significantly lower in irradiated bones (p = 0.0001). The distance between the vessels, a marker of vascular destruction, was higher after irradiation (p = 0.001). The vessels were also more altered distally after irradiation (p = 0.028). Cortical thickness was severely decreased after irradiation, sometimes even reduced to zero. Both trabecular and cortical structures were destroyed after irradiation, with wide bone gaps. Finally, both total bone volume (p = 0.0001) and cortical thickness (p = 0.0001) were significantly decreased in irradiated tibias compared to nonirradiated tibias. These results led to multiple spontaneous fractures in the irradiated group, and the destruction of intraosseous vessels observed macroscopically with the radiographic preview. This study revealed the impact of radiation on intraosseous vasculature and cortical bone with a micro-CT analysis in a rat ORN model. Hypovascularization and osteopenia are consistent with the literature, contributing a morphological scale with high resolution. Visualization of the vasculature by micro-CT is an innovative technique to see the changes after radiation, and should help adjust bone tissue engineering in irradiated bone.
上消化道癌的治疗通常需要外照射放疗。然而，辐射会以不同的敏感程度影响骨骼的所有成分，并可能产生严重的副作用，如下颌骨放射性骨坏死（ORN）。人们认为照射后骨内血管化会减少，但其对骨总体积的影响仍存在争议。本研究的目的是通过在心内注射造影剂后进行微型计算机断层扫描（micro-CT）分析，比较ORN大鼠模型与未照射大鼠的骨内血管化、皮质骨厚度和骨总体积。该研究在8周龄的Lewis 1A大鼠（n = 14）上进行。11只大鼠后肢接受单次80 Gy剂量的外照射。3只大鼠未接受照射，作为统计分析的对照。外照射8周后，所有动物在全身麻醉下接受硫酸钡心内注射。所有样本均使用分辨率为5.5μm的微型计算机断层扫描系统进行分析。图像随后进行处理以创建三维重建，并研究血管化、骨体积和皮质厚度。使用Kruskal-Wallis检验比较照射和未照射大鼠的数据。照射后无动物死亡。纳入19只照射后的胫骨和6只未照射的胫骨进行micro-CT分析。照射后骨骼中的血管百分比显著降低（p = 0.0001）。血管间距离作为血管破坏的一个指标，照射后更高（p = 0.001）。照射后血管在远端的改变也更大（p = 0.028）。照射后皮质厚度严重降低，有时甚至降至零。照射后小梁和皮质结构均被破坏，出现宽大的骨间隙。最后，与未照射的胫骨相比，照射后胫骨的骨总体积（p = 0.0001）和皮质厚度（p = 0.0001）均显著降低。这些结果导致照射组出现多处自发性骨折，并且在影像学预评估中宏观观察到骨内血管的破坏。本研究通过在大鼠ORN模型中进行micro-CT分析揭示了辐射对骨内血管系统和皮质骨的影响。血管减少和骨质减少与文献一致，提供了一个高分辨率的形态学尺度。通过micro-CT对血管系统进行可视化是一种观察辐射后变化的创新技术，应有助于调整照射后骨的骨组织工程。
