title: In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The results show a proinflammatory effect of the nitrogen-containing effect on neutrophil granulocytes which might contribute to the development of osteonecrosis.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oral- and Maxillofacial Surgery, University Medical Center, Johannes Gutenberg-University, Augustusplatz 2, 55131, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Hagelauer
authors.forename: Andreas Max
authors.initials: AM
authors.lastname: Pabst
authors.forename: Thomas
authors.initials: T
authors.lastname: Ziebart
authors.forename: Holger
authors.initials: H
authors.lastname: Ulbrich
authors.forename: Christian
authors.initials: C
authors.lastname: Walter
mesh_terms: D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology; D002633:Chemotaxis / Q000187:drug effects*; D004002:Clodronic Acid / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D005434:Flow Cytometry; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects*; D000077268:Pamidronate; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid; D000077268:Pamidronate; D000077557:Ibandronic Acid