Objectives: To determine the extent that zoledronate (ZOL) dose and duration is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ) prevalence in rice rats with generalized periodontitis (PD), characterize structural and tissue-level features of BRONJ-like lesions in this model, and examine the specific anti-resorptive role of ZOL in BRONJ.
Materials and methods: Rice rats (n = 228) consumed high sucrose-casein diet to enhance generalized PD. Groups of rats received 0, 8, 20, 50 or 125 µg/kg IV ZOL/4 weeks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n = 9-16) were necropsied after 12, 18, 24 and 30 weeks of treatment. BRONJ-like lesion prevalence and tissue-level features were assessed grossly, histopathologically and by MicroCT. ZOL bone turnover effects were assessed by femoral peripheral quantitative computed tomography, serum bone turnover marker ELISAs and osteoclast immunolabelling.
Results: Prevalence of BRONJ-like lesions was significantly associated with (a) ZOL treatment duration, but plateaued at the lowest oncologic dose, and (b) there was a similar dose-related plateau in the systemic anti-resorptive effect of ZOL. ZOL and BRONJ-like lesions also altered the structural and tissue-level features of the jaw.
Conclusion: The relationship between BRONJ-like lesion prevalence and ZOL dose and duration varies depending on the co- or pre-existing oral risk factor. At clinically relevant doses of ZOL, BRONJ-like lesions are associated with anti-resorptive activity.
Keywords: anti-resorptives; high sucrose-casein diet; histopathology; preclinical; toxicology.
© 2019 The Authors. Oral Diseases Published by John Wiley & Sons Ltd.