The effects of Zoledronate administration routes on the reproducibility of BRONJ in rodent models: A systematic review.

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a debilitating condition characterized by alveolar bone destruction associated with bisphosphonate medications, such as zoledronate. Zoledronate use is associated with an increased incidence of BRONJ. In rodent models, accurate replication of BRONJ stages depends on the route of zoledronate administration. This systematic review evaluates the reproducibility of BRONJ characteristics in rodent models by analyzing the effects of different zoledronate injection routes on clinical, histopathological, and radiological outcomes. A systematic literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using keywords related to BRONJ and zoledronate. The following data were collected from the selected studies: characteristics of mice and rats; zoledronate dose, duration, and route of administration. The BRONJ stage was determined in these studies based on clinical, histopathological, and radiological features of alveolar bone necrosis. Zoledronate treatment notably affected the reproducibility of BRONJ characteristics. Mice and rats exhibited distinct characteristics in producing BRONJ, depending on the route of zoledronate injection. Subcutaneous, intraperitoneal (IP), and intravenous (IV) injections in rats consistently produced exposed alveolar bone, the main criterion for clinical BRONJ. IP and IV zoledronate injection in mice produced a clinical BRONJ model. Neither mice nor rats exhibited differences in BRONJ characteristics according to sex. Rodent models of BRONJ mimic the staging and characteristics of BRONJ observed in humans. Rat BRONJ models were more consistently reproducible when the zoledronate administration route was tailored to achieve specific research objectives.