INTRODUCTION Long-term administration of bisphosphonates (BPs) may cause osteonecrosis of the jaw (BRONJ). After administration, 50% of BPs in the circulation rapidly binds to calcium phosphate of bone. Two forms, bound and free BPs, may affect cells residing in bone including macrophages. Therefore, the aim of this study was to examine the effects of bound and free BPs on macrophage viability. MATERIALS AND METHODS Biomaterials coated with BPs were used as a model to investigate the effect of bound BPs. For free BPs, RAW cells were plated on uncoated materials and BPs were added into the media. Cell viability and number were investigated by MTT assay and nuclei staining, respectively. Furthermore, coating and washing media were collected and were used to examine cell viability. RESULTS RAW cells grew on biomaterials for 7 days. At 3 days, free and calcium-bound BPs significantly decreased cell viability and cell number compared to control. Coating media collected from pre-incubation with BP-coated composite materials reduced macrophage cell viability. CONCLUSION This study showed that macrophages were directly affected by bound and free BPs. The presence of macrophages is mandatory for bone healing, thus the inhibition of cell viability might serve as an etiology of BRONJ.

中文翻译：

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结合的和游离的双膦酸酯对巨噬细胞活力的抑制。

简介长期服用双膦酸盐（BPs）可能会引起颌骨坏死（BRONJ）。给药后，循环中50％的BP迅速与骨骼的磷酸钙结合。结合和游离BP两种形式均可影响包括巨噬细胞在内的骨骼中的细胞。因此，本研究的目的是研究结合的和游离的BP对巨噬细胞活力的影响。材料与方法包覆有BP的生物材料被用作模型来研究结合BP的作用。对于游离的BP，将RAW细胞铺在未涂覆的材料上，并将BP添加到培养基中。通过MTT测定和细胞核染色分别研究细胞活力和数目。此外，收集涂层和洗涤介质并用于检查细胞活力。结果RAW细胞在生物材料上生长7天。在三天后 与对照相比，游离的和结合钙的BP显着降低了细胞活力和细胞数量。通过与BP涂层复合材料进行预孵育而收集的涂层介质降低了巨噬细胞的生存能力。结论这项研究表明巨噬细胞直接受到结合和游离BP的影响。巨噬细胞的存在对于骨骼愈合是必不可少的，因此抑制细胞活力可能是BRONJ的病因。