Zoledronate Treatment Duration Is Linked to Bisphosphonate‐Related ONJ Prevalence in Rice Rats with Generalized Periodontitis

Abstract

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 125μg/kg IV ZOL/4wks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n=9‐16) were necropsied after 12, 18, 24, and 30wks 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 pQCT, serum bone‐turnover marker ELISAs, and osteoclast immunolabeling.

Results

Prevalence of BRONJ‐like lesions was significantly associated with 1) ZOL treatment duration, but plateaued at the lowest oncologic dose, and 2) 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.

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