Ann Arbor, Mich. From the University of Michigan, Division of Plastic Surgery, Craniofacial Research Laboratory.
Plast Reconstr Surg. 2011 Jul;128(1):114-121. doi: 10.1097/PRS.0b013e31821741d4.
The authors' laboratory previously demonstrated that radiation significantly alters new bone formation in the murine mandible, impeding the use of distraction osteogenesis as a viable reconstructive option after radiotherapy in head and neck cancer. The authors hypothesize that the deleterious effects of radiation on regenerate formation results from a dose-response depletion of essential osteogenic cells. The authors' specific aim was to use quantitative histomorphometry to objectively measure the human equivalent dose-response effects of radiation on the integrity of the mandible's cellular and tissue composition.
Twenty Sprague-Dawley rats were randomized into three radiation dosage groups: low (5.91 Gy), middle (7 Gy), and high (8.89 Gy), delivered in five daily fractions. These dosages approximated 75, 100, and 150 percent, respectively, of the biological equivalent dose the mandible experiences in the clinical regimen of head and neck cancer patients. Hemimandibles were harvested 56 days after radiation and stained with Gomori trichrome. Quantitative histomorphometry was performed using Bioquant software and analysis with a one-way analysis of variance Kruskal-Wallis test.
The authors' data revealed a statistically significant diminution in the mean number of osteocytes. The authors also demonstrated a corresponding significant increase in the mean values of empty lacunae. Both of these quantitative histomorphometric changes demonstrated a dose-response relationship.
The authors' study supports their hypothesis that radiation induces a dose-response depletion in osteocytes and an increase in empty lacunae. These reliable and reproducible metrics can now be used to determine the efficacy of therapies aimed at safeguarding the cells essential for optimal bone regeneration and potentially enhance the use of distraction osteogenesis in head and neck cancer patients.
作者所在实验室先前的研究表明,辐射会显著改变鼠下颌骨的新骨形成,从而阻碍在头颈部癌症放疗后使用牵张成骨术作为一种可行的重建选择。作者假设,辐射对再生形成的有害影响是由于必需成骨细胞的剂量反应性耗竭所致。作者的具体目标是使用定量组织形态计量学来客观测量辐射对下颌骨细胞和组织成分完整性的人等效剂量反应。
20 只 Sprague-Dawley 大鼠随机分为三组辐射剂量组:低(5.91 Gy)、中(7 Gy)和高(8.89 Gy),每天分为 5 个剂量。这些剂量分别约为头颈部癌症患者临床方案中下颌骨所经历的生物学等效剂量的 75%、100%和 150%。辐射后 56 天采集半下颌骨并用 Gomori 三色染色。使用 Bioquant 软件进行定量组织形态计量学,并使用单向方差分析 Kruskal-Wallis 检验进行分析。
作者的数据显示,成骨细胞的平均数量明显减少。作者还证明了空陷窝的平均数值相应显著增加。这两种定量组织形态计量学变化均表现出剂量反应关系。
作者的研究支持他们的假设,即辐射诱导成骨细胞的剂量反应性耗竭和空陷窝的增加。这些可靠且可重复的指标现在可用于确定旨在保护对最佳骨再生至关重要的细胞的治疗方法的疗效,并可能增强头颈部癌症患者使用牵张成骨术的能力。