Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.
Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.
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DOI：
10.1016/j.bone.2015.12.051
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发表时间：
2016-03
期刊：
影响因子：
4.1
通讯作者：
Buchman SR
中科院分区：
文献类型：
--
作者：
Donneys A;Nelson NS;Perosky JE;Polyatskaya Y;Rodriguez JJ;Figueredo C;Vasseli CA;Ratliff HC;Deshpande SS;Kozloff KM;Buchman SR
病理性骨折和相关的骨不连发生在以前的辐射骨是严重的衰弱性疾病。尽管已知辐射对健康组织细胞结构和血管分布具有有害作用，但目前还没有临床上可接受的药物干预措施来靶向骨组织内的这些破坏机制。我们利用amifostine-一种细胞辐射防护剂-和去铁胺-一种血管生成刺激剂-在照射后下颌骨骨折修复的大鼠模型中同时靶向照射骨内的细胞和血管龛。将联合治疗的大鼠与接受单一氨磷汀或去铁胺治疗的大鼠、未治疗/辐照动物（XFx）和未治疗/未辐照动物（Fx）进行比较。利用3D血管造影建模、组织学、骨矿物质密度分布和力学指标评估治疗效果。当比较XFx和单独的Fx时，我们观察到所有结果的指标都减少了，表明辐射的破坏性影响。在所有结果中，只有联合治疗组改善了XFx水平，将所有指标标准化为Fx水平，并且始终与其他治疗方案一样好或上级其他治疗方案（p< 0.05）。总的来说，我们的数据表明，靶向照射骨内的细胞和血管环境的骨保护剂可防止骨损伤并促进骨折愈合。
Pathologic fractures and associated non-unions arising in previously irradiated bone are severely debilitating diseases. Although radiation is known to have deleterious effects on healthy tissue cellularity and vascularity, no clinically accepted pharmacologic interventions currently exist to target these destructive mechanisms within osseous tissues. We utilized amifostine—a cellular radioprotectant—and deferoxamine—an angiogenic stimulant—to simultaneously target the cellular and vascular niches within irradiated bone in a rat model of mandibular fracture repair following irradiation. Rats treated with combined therapy were compared to those undergoing treatment with singular amifostine or deferoxamine therapy, nontreated/irradiated animals (XFx) and non-treated/non-irradiated animals (Fx). 3D angiographic modeling, histology, Bone Mineral Density Distribution and mechanical metrics were utilized to assess therapeutic efficacy. We observed diminished metrics for all outcomes when comparing XFx to Fx alone, indicating the damaging effects of radiation. Across all outcomes, only the combined treatment group improved upon XFx levels, normalized all metrics to Fx levels, and was consistently as good as, or superior to the other treatment options (p< 0.05). Collectively, our data demonstrate that pharmacologically targeting the cellular and vascular environments within irradiated bone prevents bone injury and enhances fracture healing.