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Effects of zoledronate regimen on the induction of BRONJ in rats
Author(s) -
Elsalanty Mohammed,
Daoudi Asma,
Howie Nicole,
Panos Anastasia,
Kurago Zoya
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1039.13
Subject(s) - medicine , zoledronic acid , bisphosphonate , osteoclast , regimen , osteonecrosis of the jaw , saline , osteoporosis , urology , receptor
Background Bisphosphonate‐Related Osteonecrosis of the Jaw (BRONJ) has been reported in patients undergoing long‐term bisphosphonate treatement. So far, no biological mechanism has been shown to explain the condition. This study compared the induction of the clinical features of BRONJ between two zoledronic acid (ZA) regimens. We hypothesized that duration of treatment would be more important than the dose of ZA for the induction of BRONJ. Methods We included 80 female Sprague‐Dawley rats in four groups (20 rats‐each): Group 1 received 80μg/kg of intravenous ZA weekly for 13 weeks, group 2 received 150μg/kg ZA daily for 16 consecutive days, while groups 3 and 4 received corresponding injections of saline for the same durations. At the end of the treatment period, the first and second mandibular molars were extracted. Animals were sacrificed at 1, 2, 4, and 8 weeks. The study analyzed the therapeutic effect of treatment on vertebral bone quality, the features of BRONJ, and the toxic effects on the liver and kidneys. Results There was an increase in the cortical thickness and area fraction of the vertebra in the ZA‐treated animals at 1 and 8 weeks post extraction compared to the controls. This “therapeutic” effect was more pronounced in the lower ZA dose. On the other hand, All ZA‐treated animals manifested the clinical, histological, and radiographic features of BRONJ. There was a significant decline in osteoclast activity in the treatment groups at 1‐week. The higher dose had a more persistent decline in osteoclast recruitment at 8 weeks. Conclusions Both doses induced BRONJ in all treated animals. The shorter, high‐dose course of ZA had less therapeutic effect and induced features of organ toxicity. The longer, lower dose of ZA provides a superior translational model for BRONJ. Support or Funding Information This study was supported by NIA 1P01AG036675, a Georgia Regents University Extramural Success Award (ESA), the Fort Gordon Periodontology Command, the Center for Undergraduate Research and Scholarship and the Honors Program at Georgia Regents University.