Mohammad Zandi1, Arash Dehghan2, Hamid Malekzadeh3, Pejman Janbaz4, Khaled Ghadermazi4, Payam Amini5. 1. Department of Oral and Maxillofacial Surgery, Hamedan University of Medical Sciences, Hamedan, Iran; Dental Research Center, Hamedan University of Medical Sciences, Hamedan, Iran. 2. Department of Pathology, Hamedan University of Medical Sciences, Hamedan, Iran. 3. Department of Oral and Maxillofacial Surgery, Hamedan University of Medical Sciences, Hamedan, Iran. Electronic address: hamid_malekzadeh_28@yahoo.com. 4. Department of Oral and Maxillofacial Surgery, Hamedan University of Medical Sciences, Hamedan, Iran. 5. Department of Biostatistics, Hamedan University of Medical Sciences, Hamedan, Iran.
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.
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.
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