Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
Department of Medical Technical Support, NCO School of Army Medical University, Shijiazhuang, China.
Braz J Med Biol Res. 2021 Oct 29;54(12):e11550. doi: 10.1590/1414-431X2021e11550. eCollection 2021.
Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of the diabetic patients following radiotherapy. After one month of streptozotocin injection, three-month-old male rats were subjected to focal radiotherapy (8 Gy, twice, at days 1 and 3), and then bone mass, microarchitecture, and turnover as well as bone cell activities were evaluated at 2 months post-irradiation. Micro-computed tomography results demonstrated that DM rats exhibited greater deterioration in trabecular bone mass and microarchitecture following irradiation compared with the damage to bone structure induced by DM or radiotherapy. The serum biochemical, bone histomorphometric, and gene expression assays revealed that DM combined with radiotherapy showed lower bone formation rate, osteoblast number on bone surface, and expression of osteoblast-related markers (ALP, Runx2, Osx, and Col-1) compared with DM or irradiation alone. DM plus irradiation also caused higher bone resorption rate, osteoclast number on bone surface, and expression of osteoclast-specific markers (TRAP, cathepsin K, and calcitonin receptor) than DM or irradiation treatment alone. Moreover, lower osteocyte survival and higher expression of Sost and DKK1 genes (two negative modulators of Wnt signaling) were observed in rats with combined DM and radiotherapy. Together, these findings revealed a higher deterioration of the diabetic skeleton following radiotherapy, and emphasized the clinical importance of health maintenance.
放射治疗后，患者的骨量减少，脆性骨折的风险增加。糖尿病（DM）也被报道对骨结构和质量有不良影响。然而，目前还没有临床或实验研究系统地描述放射治疗后糖尿病患者的骨骼表型。在链脲佐菌素注射一个月后，3 月龄雄性大鼠接受局部放射治疗（8 Gy，两次，在第 1 天和第 3 天），然后在照射后 2 个月评估骨量、微结构和转换以及骨细胞活性。微计算机断层扫描结果表明，与 DM 或放射治疗引起的骨结构损伤相比，DM 大鼠在照射后表现出更严重的小梁骨量和微结构恶化。血清生化、骨组织形态计量学和基因表达检测结果表明，与 DM 或放射治疗单独相比，DM 联合放射治疗显示出更低的骨形成率、骨表面成骨细胞数量和骨形成相关标志物（碱性磷酸酶、Runx2、Osx 和 Col-1）的表达。DM 联合放射治疗还导致更高的骨吸收率、骨表面破骨细胞数量和破骨细胞特异性标志物（TRAP、组织蛋白酶 K 和降钙素受体）的表达。此外，在 DM 联合放射治疗的大鼠中，还观察到较低的骨细胞存活率和更高的 Sost 和 DKK1 基因（Wnt 信号的两个负调节剂）表达。综上所述，这些发现揭示了放射治疗后糖尿病骨骼的恶化程度更高，强调了保持健康的临床重要性。
