In vivo effects of zoledronic acid on oral mucosal epithelial cells

E. Allam, M. R. Allen, T. M. Chu, A. Ghoneima, L. Jack Windsor

Research output: Contribution to journalArticle

18 Scopus citations


Objective: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis, and matrix metalloproteinases (MMPs) expression in oral mucosal epithelial cells. Methods: One-year-old dogs were either untreated (control group) or given high doses of intravenous ZA (ZA group) for 3months. The doses of ZA were equivalent to those given to cancer patients, yet were administered two times more frequently (every 2weeks). Mucosal tissues were assessed immunohistochemically for cell proliferation (proliferating cell nuclear antigen, PCNA), matrix metalloproteinase (MMP) expression, and apoptosis (caspase 3 and TUNEL). Results: There were no significant differences between the groups with respect to PCNA, MMP-2, MMP-14, and TUNEL positive cells. However, the expression of MMP-9 was significantly higher in the control group than in the ZA group (P<0.05), whereas the expression of caspase 3 was significantly lower in the control group than in the ZA group (P<0.05). Conclusion: These results suggest that high doses of ZA resulted in higher levels of apoptosis and lower levels of MMP-9 in the oral epithelial cells supporting the idea of bisphosphonate treatment affects the oral mucosa.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalOral Diseases
Issue number3
StatePublished - Apr 1 2011


  • Oral epithelial cells
  • Osteonecrosis of the jaws
  • Zoledronic acid

ASJC Scopus subject areas

  • Dentistry(all)
  • Otorhinolaryngology

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