• Sebastian Hoefert, Claudia Sade Hoefert, Adelheid Munz, Inge Schmitz, Martin Grimm, Anna Yuan, Hinnak Northoff, Siegmar Reinert, and Dorothea Alexander.
• Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Tuebingen, Germany. Electronic address: sebastian.hoefert@med.uni-tuebingen.de.
• Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Mar 1; 121 (3): 222-32.

ObjectivesImmune deficiency and bacterial infection have been suggested to play a role in the pathophysiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Zoledronate was previously found to promote THP-1 cell death. To examine this hypothesis with all commonly prescribed bisphosphonates, we tested the effect of (nitrogen-containing) ibandronate, risedronate, alendronate, pamidronate, and (non-nitrogen-containing) clodronate on macrophagic THP-1 cells.Study DesignActivated THP-1 cells were exposed to .5 to 50 μM of nitrogen-containing bisphosphonates and .5 to 500 μM of clodronate. Cell adherence and survival were assessed in vitro using the xCELLigence real-time monitoring system. Results were confirmed histologically and verified with Live/Dead staining.ResultsAll bisphosphonates inhibited THP-1 cell adherence and survival dose and time dependently, significant for zoledronate, alendronate, pamidronate, and clodronate in high concentrations (50 μM and 500 μM; P < .05). Low concentrations (0.5 μM) of risedronate, alendronate, and pamidronate prolonged the inflexion points of THP-1 cell survival compared with controls (P < .05). THP-1 cells exhibited no cytomorphologic changes at all concentrations.ConclusionsCommonly prescribed bisphosphonates inhibit the survival of macrophagic THP-1 cells dose-dependently without altering morphology. This may suggest a local immune dysfunction reflective of individual bisphosphonate potency leading to the pathogenesis of BRONJ.Copyright © 2016 Elsevier Inc. All rights reserved.

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