1. Zoledronic acid enhances tumor growth and metastatic spread in a mouse model of jaw osteosarcoma.
- Author
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Nham TT, Guiho R, Brion R, Amiaud J, Le Royer BB, Gomez-Brouchet A, Rédini F, and Bertin H
- Subjects
- Animals, Mice, RANK Ligand metabolism, Disease Models, Animal, Vascular Endothelial Growth Factor A metabolism, Tartrate-Resistant Acid Phosphatase metabolism, Receptor Activator of Nuclear Factor-kappa B metabolism, X-Ray Microtomography, Tumor Burden drug effects, Osteolysis drug therapy, Zoledronic Acid therapeutic use, Zoledronic Acid pharmacology, Osteosarcoma drug therapy, Osteosarcoma pathology, Bone Density Conservation Agents pharmacology, Bone Density Conservation Agents therapeutic use, Diphosphonates pharmacology, Diphosphonates therapeutic use, Imidazoles pharmacology, Lung Neoplasms pathology, Lung Neoplasms secondary, Lung Neoplasms drug therapy, Jaw Neoplasms pathology, Jaw Neoplasms drug therapy
- Abstract
Objectives: Investigation of the therapeutic effect of zoledronic acid (ZA) in a preclinical model of jaw osteosarcoma (JO)., Materials and Methods: 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., Results: Animals receiving ZA exhibited an increased tumor volume compared with nontreated animals (71.3 ± 14.3 mm
3 vs. 51.9 ± 19.9 mm3 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 mm3 in the ZA group vs. 11.55 ± 1.18 mm3 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., Conclusion: 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., (© 2024 The Authors. Oral Diseases published by Wiley Periodicals LLC.)- Published
- 2024
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