Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Orthopaedics, Otto-von-Guericke-University, Magdeburg, Germany.
J Biomed Mater Res A. 2020 Aug 1;108(8):1774-1786. doi: 10.1002/jbm.a.36944. Epub 2020 Apr 21.
Bisphosphonates (BPs) target osteoclasts, slowing bone resorption thus providing rationale to support osseointegration. However, BPs may negatively affect osteoblasts, impairing peri-implant bone formation. The goal of this study was to assess the effects BPs have on surface-mediated osteogenesis of osteoblasts. MG63 cells were cultured on 15-mm grade 2 titanium disks: smooth, hydrophobic-microrough, or hydrophilic-microrough (Institut Straumann AG, Basel, Switzerland). Tissue culture polystyrene (TCPS) was used as a control. At confluence, cells were treated with 0, 10 , 10 , and 10 M of alendronate, zoledronate, or ibandronate for 24 hr. Sprague Dawley rats were also treated with 1 μg/kg/day ibandronate or phosphate-buffered saline control for 5 weeks. Calvarial osteoblasts (rat osteoblasts [rOBs]) were isolated, characterized, and cultured on surfaces. Osteogenic markers in the media were quantified using ELISAs. BP treatment reduced osteocalcin, osteoprotegerin, osteopontin, bone morphogenetic protein-2, prostaglandin E , transforming growth factor β1, interleukin 10, and vascular endothelial growth factor in MG63 cells. The effect was more robust on rough surfaces, and higher concentrations of BPs stunted production to TCPS/PT levels. Ibandronate conditioned rOBs produced less osteogenic markers similar to direct BP treatment. These results suggest that BP exposure jeopardizes the pro-osteogenic response osteoblasts have to microstructured surfaces. Their effects persist in vivo and negatively condition osteoblast response in vitro. Clinically, BPs could compromise osseointegration.
双膦酸盐（BPs）靶向破骨细胞，减缓骨吸收，从而为支持骨整合提供了依据。然而，BPs 可能会对成骨细胞产生负面影响，损害种植体周围骨形成。本研究旨在评估 BPs 对成骨细胞表面介导的成骨作用的影响。将 MG63 细胞培养在 15mm 级 2 型钛盘上：光滑、疏水性微粗糙或亲水性微粗糙（Institut Straumann AG，巴塞尔，瑞士）。组织培养聚苯乙烯（TCPS）用作对照。在汇合时，用 0、10、10 和 10 M 的阿仑膦酸盐、唑来膦酸盐或伊班膦酸盐处理细胞 24 小时。还对 Sprague Dawley 大鼠用 1μg/kg/天伊班膦酸盐或磷酸盐缓冲盐水对照处理 5 周。分离、鉴定并在表面培养颅盖骨成骨细胞（大鼠成骨细胞[rOBs]）。使用 ELISA 定量培养基中的成骨标志物。BP 处理降低了 MG63 细胞中的骨钙素、骨保护素、骨桥蛋白、骨形成蛋白-2、前列腺素 E、转化生长因子β1、白细胞介素 10 和血管内皮生长因子。在粗糙表面上的效果更明显，并且更高浓度的 BP 使产量减少到 TCPS/PT 水平。伊班膦酸盐调节 rOBs 产生的成骨标志物与直接 BP 处理相似。这些结果表明，BP 暴露危及成骨细胞对微结构表面的促成骨反应。它们的作用在体内持续存在，并在体外对成骨细胞反应产生负面影响。临床上，BPs 可能会影响骨整合。
