Clinical Oral Investigations

, Volume 19, Issue 1, pp 139–148 | Cite as

In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes

  • Nadine Hagelauer
  • Andreas Max Pabst
  • Thomas Ziebart
  • Holger Ulbrich
  • Christian Walter
Original Article



Bisphosphonate-associated osteonecrosis of the jaws is a serious side effect that mainly occurs in patients receiving highly potent, nitrogen-containing bisphosphonates. Usually the diagnosis is made due to exposed bone and a nonhealing wound. Neutrophil granulocytes are essential for sufficient wound healing; therefore, the influence of different bisphosphonates on neutrophil granulocytes was the focus of this study.

Material and methods

The effect of nitrogen-containing bisphosphonates (ibandronate, pamidronate, and zoledronate) and one non-nitrogen-containing bisphosphonate (clodronate) on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes in human whole blood was analyzed using standard cytometric flow assays.


Chemotaxis of neutrophils was reduced by almost 50 % when cells were treated with ibandronate and zoledronate. All tested nitrogen-containing bisphosphonates moderately increased the percentage of phagocytizing neutrophils, whereas the percentage of oxidizing cells was extremely affected. Zoledronate increased the oxidative burst activity even at low concentrations. Treatment with ibandronate and pamidronate reached the same level, but only in at least 10 times the higher concentrations. The maximal burst activity of a single cell reached nearly 150 % compared to control. In this case, zoledronate also caused maximal effects even at low concentrations. Clodronate did not show any effects.


The results show a proinflammatory effect of the nitrogen-containing effect on neutrophil granulocytes which might contribute to the development of osteonecrosis.

Clinical relevance

The altered neutrophil defense might play a key role in the pathogenesis of bisphosphonate-associated osteonecrosis of the jaws, although the underlying causation between inflammatory reaction and the development of necrosis is yet unknown.


Bisphosphonate Bisphosphonate-associated osteonecrosis of the jaws Neutrophil granulocyte Immune defense 


Conflict of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Nadine Hagelauer
    • 1
  • Andreas Max Pabst
    • 1
  • Thomas Ziebart
    • 1
  • Holger Ulbrich
    • 2
  • Christian Walter
    • 1
  1. 1.Oral- and Maxillofacial Surgery, University Medical CenterJohannes Gutenberg-UniversityMainzGermany
  2. 2.Institute of Pharmacy and BiochemistryJohannes Gutenberg-UniversityMainzGermany

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