Chronic treatment with zoledronic acid increases inflammatory markers in periodontium of rats

Background: Bisphosphonates (BF) rise proinflammatory markers and irreversibly bind to bone. Chronically, BF can lead to an inflammatory status and can increase the local oxidative stress in periodontium. Therefore, the objective of this study was to evaluate whether the chronic infusion of Zoledronic Acid (ZA) increases inflam- matory markers in periodontium of rats. Methods and results: Chronically, infusion therapy was performed with ZA (0.04, 0.2 or 1 mg/kg or saline) by four doses in over a 70-day period to analyze periodontium of the first right inferior molar using histologic, histochemical (toluidine blue), and immunohistochemical (CD68, tumor necrosis factor- a (TNF-a), interleukin-1beta (IL- 1b), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kB)) tests. The experiment was replicated (ZA 0.2 mg/kg versus saline) for myeloperoxidase (MPO) assay and dose TNF-a, IL-1b, malondialdehyde (MDA) and glutathione (GSH) in gingiva of the same tooth. Despite there is no alteration in mast cells (P = .608) and CD68 mononuclear-positive cells (P = .351), in the periodontium of the ZA-treated group, was observed an increase in the presence of inflammatory cells (P = .001) and cytoplasmic immunostaining for TNF-a (P = .003), IL-1b (P = .004), iNOS (P = .008), and NF-kB (P = .025). Levels of MPO (P < .001), TNF-a (P = .002), IL-1b (P < .001), and GSH (P = .005) were augmented in gingiva of ZA-treated group but MDA (P = .993) levels and NF-kB nuclear staining (P = .923) were not altered. Conclusions: Chronic treatment with ZA increase proinflammatory cytokines and the number of inflammatory cells in periodontium of rats and GSH are expressed probably in a compensatory manner