Effect of bisphosphonates on macrophagic THP-1 cell survival in bisphosphonate-related osteonecrosis of the jaw (BRONJ)

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• 作者：Sebastian Hoefert ; MD ; DMD^a ; ^{sebastian.hoefert@med.uni-tuebingen.de" class="auth_mail" title="E-mail the corresponding author} ; Claudia Sade Hoefert ; DMD^a ; Adelheid Munz ; MTA^a ; Inge Schmitz ; PhD^b ; Martin Grimm ; MD ; DMD^a ; Anna Yuan ; DMD^a ; Hinnak Northoff ; MD ; PhD^c ; Siegmar Reinert ; MD ; DMD^a ; Dorothea Alexander ; PhD^a
• 刊名：Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：121
• 期：3
• 页码：222-232
• 全文大小：4094 K

文摘

Immune 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 Design

Activated 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.

Results

All 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.

Conclusions

Commonly 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.