Zoledronic acid enhances tumor growth and metastatic spread in a mouse model of jaw osteosarcoma

ObjectivesInvestigation of the therapeutic effect of zoledronic acid (ZA) in a preclinical model of jaw osteosarcoma (JO).Materials and MethodsThe effect of 100 mu g/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.ResultsAnimals receiving ZA exhibited an increased tumor volume compared with nontreated animals (71.3 +/- 14.3 mm3 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.ConclusionThe 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.