Craniofacial Research Laboratory, University of Michigan, 2228 BSRB, 109 Zina Pitcher, Ann Arbor 48109, USA.
Radiat Oncol. 2012 Sep 7;7:151. doi: 10.1186/1748-717X-7-151.
The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.
虽然有一些轶事病例报告显示，头颈部癌症放射治疗后使用下颌骨牵引成骨术有混合结果，但辐射组织支持骨生长的能力仍未得到明确界定。这些报告中的许多都缺乏客观的衡量标准，无法充分分析结果或疗效。本实验的目的是利用大剂量和高分割放射治疗后下颌骨牵引成骨的大鼠模型，并在这些条件下评估和量化牵引骨的形成。雄性 Sprague-Dawley 大鼠接受左下颌骨的 12 次外束放射治疗（48 Gray）。经过两周的恢复期，应用外固定架牵开器，并逐渐牵开下颌骨。在 28 天的巩固期后采集组织。进行了大体、放射学和组织学评估。那些接受术前放射治疗的动物表现出骨形成的严重衰减，包括骨萎缩、牵引间隙不完全桥接以及明显的骨缺损或骨不连。尽管实现了物理延长，但辐射后的骨骼始终对牵引成骨过程中的正常骨改建过程产生明显的损伤作用。该鼠模型为高剂量辐射对牵张成骨中骨修复和再生的损伤作用提供了可靠的证据，利用准确和可重复的指标。这些结果现在可用于帮助开发针对减轻辐射对骨再生的不利影响的治疗方法，并优化牵张成骨术，以便成功应用于肿瘤后重建。
