Ann Arbor, Mich.; and Columbia, S.C. From the Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan; and the Department of Surgery, University of South Carolina School of Medicine.
Plast Reconstr Surg. 2013 Oct;132(4):542e-548e. doi: 10.1097/PRS.0b013e31829fe548.
The authors' laboratory has previously demonstrated that deferoxamine promotes angiogenesis and bone repair in the setting of radiation therapy coupled with distraction osteogenesis. However, clinically relevant effects of deferoxamine administration on union rate and micro-computed tomographic and biomechanical parameters are unknown. The authors posit that administration of deferoxamine will increase union rate, mineralization, and strength of the regenerate in an irradiated distraction osteogenesis model.
Sprague-Dawley rats were randomized into three groups: distraction osteogenesis-control, distraction osteogenesis-radiation therapy, and distraction osteogenesis-radiation therapy-deferoxamine. All animals underwent an osteotomy and distraction osteogenesis across a 5.1-mm distraction gap. Irradiated animals received 35-Gy human-equivalent radiation therapy 2 weeks before surgery, and deferoxamine was injected postoperatively in the regenerate site of treatment animals. Animals were killed on postoperative day 40, and mandibles were harvested to determine rates of bony union and micro-computed tomographic and biomechanical parameters.
Compared with irradiated mandibles, deferoxamine-treated mandibles exhibited a higher union rate (11 percent versus 92 percent, respectively). Across micro-computed tomographic and biomechanical parameters, significant diminutions were observed with administration of radiation therapy, whereas deferoxamine therapy resulted in significant restoration to levels of controls, with select metrics exhibiting significant increases even beyond controls.
The authors' data confirm that deferoxamine restores clinically relevant metrics of bony union and micro-computed tomographic and biomechanical parameters in a model of irradiated distraction osteogenesis in the murine mandible. Their findings support a potential use for deferoxamine in treatment protocols to allow predictable and reliable use of distraction osteogenesis as a viable reconstructive option in patients with head and neck cancer.
作者实验室先前的研究表明,去铁胺在放射治疗联合牵张成骨的情况下可促进血管生成和骨修复。然而,去铁胺给药对愈合率以及微计算机断层扫描和生物力学参数的临床相关影响尚不清楚。作者推测,在放射诱导的牵张成骨模型中,去铁胺的给药将增加愈合率、再生骨的矿化和强度。
将 Sprague-Dawley 大鼠随机分为三组:牵张成骨对照组、牵张成骨放射治疗组和牵张成骨放射治疗去铁胺组。所有动物均接受 5.1mm 牵开间隙的截骨和牵张成骨手术。照射动物在手术前 2 周接受 35Gy 人等效放射治疗,并且在治疗动物的再生部位术后注射去铁胺。术后第 40 天处死动物,采集下颌骨以确定骨融合率以及微计算机断层扫描和生物力学参数。
与照射下颌骨相比,去铁胺治疗的下颌骨表现出更高的融合率(分别为 11%和 92%)。在微计算机断层扫描和生物力学参数方面,放射治疗后观察到明显的减少,而去铁胺治疗则导致恢复到对照组水平,一些指标甚至超过了对照组。
作者的数据证实,去铁胺可恢复受照射的牵张成骨模型中与临床相关的骨融合以及微计算机断层扫描和生物力学参数,在小鼠下颌骨中。他们的研究结果支持将去铁胺用于治疗方案,以允许将牵张成骨作为头颈部癌症患者可行的重建选择进行可靠和可预测的使用。