Introducing a protocol to create bisphosphonate-related osteonecrosis of the jaw in rat animal model.

Abstract

OBJECTIVE: Previously published animal investigations on bisphosphonate-related osteonecrosis of the jaws (BRONJ) showed a variety of methods for BRONJ induction and inconsistent findings. The aim of present study was to develop a reliable protocol for BRONJ induction in rat animal model. SUBJECTS AND METHODS: In a pilot study, 64 rats were randomly divided into 4 groups and 16 subgroups (each containing 2 experimental and 2 control rats) based on the timing of tooth extraction and euthanasia. The experimental and control rats received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week until sacrificed, and evaluated for presence of bone exposure clinically, and osteonecrosis and new bone formation histologically. The protocol that successfully produced BRONJ in pilot study was tested in a randomized controlled experimental investigation using 45 rats. RESULTS: In pilot investigation, the highest rate of BRONJ was obtained after four weekly zoledronate injections, at least 4 weeks after tooth extraction. The randomized controlled experimental study verified this finding with a success rate of 83%, and also showed that more prolongation of zoledronate therapy did not increase the BRONJ rate. CONCLUSION: The protocol developed in the present study could be used reliably for future BRONJ investigations on rats.