Development of models of preclinical stage 2 bisphosphonate-related osteonecrosis of the jaw in non-rodent mammals using zoledronate: A systematic review.

OBJECTIVE

To identify specific experimental parameters, including species selection, zoledronate dosing regimens, and surgical triggers, required to reliably reproduce advanced clinical stages of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in non-rodent mammals.

DESIGN

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched for studies reporting the use of zoledronate-treated non-rodent mammals subjected to dental trauma. Extracted variables included species, dosing, intervention, clinical exposure, histopathology, and micro-CT findings.

RESULTS

Twenty-three studies were included. High-dose intravenous zoledronate combined with posterior tooth extraction consistently induced stage 2 BRONJ across various species, including minipigs, dogs, and sheep. Key findings included persistent bone exposure, increased empty osteocytic lacunae, and necrotic bone areas.

CONCLUSIONS

Standardized protocols using large animal models effectively mimic human stage 2 BRONJ, providing a reliable platform for translational research and the development of new therapeutic strategies.