Nantes Université, CHU Nantes, Service de Chirurgie Maxillo-Faciale et Stomatologie, Nantes, France.
Nantes Université, Univ Angers, CHU Nantes, INSERM, CNRS, CRCI2NA, Nantes, France.
Oral Dis. 2024 Oct;30(7):4209-4219. doi: 10.1111/odi.14897. Epub 2024 Feb 20.
Investigation of the therapeutic effect of zoledronic acid (ZA) in a preclinical model of jaw osteosarcoma (JO).
The effect of 100 μg/kg ZA administered twice a week was assessed in a xenogenic mouse model of JO. The clinical (tumor growth, development of lung metastasis), radiological (bone microarchitecture by micro-CT analysis), and molecular and immunohistochemical (TRAP, RANK/RANKL, VEGF, and CD146) parameters were investigated.
Animals receiving ZA exhibited an increased tumor volume compared with nontreated animals (71.3 ± 14.3 mm vs. 51.9 ± 19.9 mm at D14, respectively; p = 0.06) as well as increased numbers of lung metastases (mean 4.88 ± 4.45 vs. 0.50 ± 1.07 metastases, respectively; p = 0.02). ZA protected mandibular bone against tumor osteolysis (mean bone volume of 12.81 ± 0.53 mm in the ZA group vs. 11.55 ± 1.18 mm in the control group; p = 0.01). ZA induced a nonsignificant decrease in mRNA expression of the osteoclastic marker TRAP and an increase in RANK/RANKL bone remodeling markers.
The use of bisphosphonates in the therapeutic strategy for JO should be further explored, as should the role of bone resorption in the pathophysiology of the disease.
研究唑来膦酸（ZA）在颌骨骨肉瘤（JO）临床前模型中的治疗效果。
在异种移植的 JO 小鼠模型中评估每周两次给予 100μg/kg ZA 的效果。研究了临床（肿瘤生长、肺转移发展）、影像学（通过 micro-CT 分析骨微观结构）和分子及免疫组织化学（TRAP、RANK/RANKL、VEGF 和 CD146）参数。
与未治疗动物相比，接受 ZA 的动物的肿瘤体积增加（第 14 天分别为 71.3±14.3mm 和 51.9±19.9mm；p=0.06），肺转移数量也增加（平均 4.88±4.45 个与 0.50±1.07 个转移灶；p=0.02）。ZA 保护下颌骨免受肿瘤性骨溶解（ZA 组的平均骨体积为 12.81±0.53mm，而对照组为 11.55±1.18mm；p=0.01）。ZA 诱导破骨细胞标志物 TRAP 的 mRNA 表达无显著降低，而 RANK/RANKL 骨重塑标志物增加。
应进一步探讨在 JO 治疗策略中使用双膦酸盐，以及骨吸收在疾病病理生理学中的作用。
