Development of a rat model of bisphosphonate-related osteonecrosis of the Jaw (BRONJ)

Karen L. Marino, Ibrahim Zakhary, Rafik A. Abdelsayed, Jared A. Carter, Jack C. O'Neill, Rania M. Khashaba, Mohammed Elsalanty, Mark R. Stevens, James L. Borke

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The purpose of this study was to develop a rat model predictive of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats were randomized into 2 groups, control and experimental. The experimental group received 2 intravenous injections of zoledronate (20 lg/kg). The mesial root of the right mandibular first molar was extracted. Rats were euthanized at 0, 4, and 8 weeks. Bone mineral density (BMD), collagen breakdown (pyridinium [PYD]), vascular regeneration (VEGF), and histology were examined. A trend toward higher PYD values was suggested in control vs experimental groups after wounding. Serum VEGF increased significantly after wounding for both control and experimental groups. After 8 weeks, VEGF continued to rise for the experimental group only. In the extraction socket area, BMD was significantly lower after wounding in control vs. zoledronate-treated rats. Histology sections from experimental groups showed bacteria and bone necrosis. Consistent findings of BRONJ features similar to those in humans were observed after zoledronate treatment.

Original languageEnglish (US)
Pages (from-to)511-518
Number of pages8
JournalJournal of Oral Implantology
Issue numberSUPPL. 1
StatePublished - 2012


  • Bisphosphonate
  • Osteonecrosis of the jaw
  • Rat model

ASJC Scopus subject areas

  • Oral Surgery


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