Vascular alterations in the sprague-dawley rat mandible during intravenous bisphosphonate therapy

Chestine S. Guevarra, James L. Borke, Mark R. Stevens, Fredrick C. Bisch, Ibrahim Zakhary, Regina Messer, Robert C. Gerlach, Mohammed E. Elsalanty

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Long-term use of intravenous bisphosphonates, such as zoledronic acid (zoledronate), has been linked to bisphosphonate-related osteonecrosis of the jaw (BRONJ). Invasive dental surgery seems to trigger the bone necrosis in most cases. To determine the effects of zoledronic acid on the vascular structure of the rat mandible. Extracted of the mandibular first molar in rats that received 2 IV injections of zoledronate (20 μg/kg), 4 weeks apart. Zoledronate-treated rats (n = 18) were then compared to a control group of untreated rats (n = 18). At the fourth, eighth, and 12th week after molar extraction, 8 rat mandibles from each group were perfused with 35% radiopaque triphenylbismuth in methyl methacrylate via carotid artery perfusion. Mandibles were harvested and examined by micro-CT to assess the spatial and dimensional changes of the vasculature as a result of zoledronate treatment. The micro-CT analysis showed that zoledronic acid-treated rats had blood vessels that were thicker, less connected, and less ordered than control rats that were not exposed to zoledronic acid. This study demonstrated that treatment with zoledronic acid in rats is associated with vascular changes in alveolar bone. Further studies are underway to explore whether these vascular changes contribute to the pathogenesis of BRONJ.

Original languageEnglish (US)
Pages (from-to)e24-e29
JournalJournal of Oral Implantology
Issue number2
StatePublished - Apr 1 2015


  • Bisphosphonate
  • Mandible
  • Rat model
  • Vascular parameters

ASJC Scopus subject areas

  • General Medicine


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