Zoledronic Acid Modulates Cytokine Expression and Mitigates Bone Loss during the Development of Induced Apical Periodontitis in a Mice Model

Introduction Bisphosphonates are antiresorptive drugs used worldwide to treat systemic bone pathologies. This study aimed to assess the impact of zoledronic acid on the progression of induced apical periodontitis and expression of cytokines IL-1β, IL-10, IL-6 and TNF-α, in a mice model. Methods Sixteen female isogenic BALB/c mice 6 weeks age were distributed into two groups: mice with induced apical periodontitis (AP group, n = 8); and mice with induced apical periodontitis treated with zoledronic acid (AP-ZA group, n = 8). AP-ZA group received a dose of 125 μg/Kg of zoledronic acid diluted in sterile saline solution administrated intraperitoneally once a week for four weeks before pulp exposure, while AP group received only saline solution. Pulp exposures were performed on the maxillary first molars for induction of apical periodontitis and mice were euthanized after 7 and 21 days. The jaws were collected, scanned using micro-CT and processed for polymerase chain reaction (PCR) analysis of interleukins IL-1β, IL-10, IL-6, and TNF-α. Student t-test was performed for parametric data, and Mann-Whitney tests were used for non-parametric data. The level of significance was set at 5%. Results Micro-CT revealed higher bone resorption in AP group compared to AP-ZA group in both time-points (P<0.05). Real-time PCR demonstrated higher TNF-α expression in AP group in both time points, and higher IL-6 and IL-1β expression in AP group at 7 and 21 time-points, respectively, compared to AP-ZA group (P<0.05). No differences were observed regarding IL-10 expression between the groups. Conclusion Zoledronic acid had significant anti-inflammatory and anti-resorptive effects on apical periodontitis in mice.