Greiner Stefan, Kadow-Romacker Anke, Wildemann Britt, Schwabe Philipp, Schmidmaier Gerhard
Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Germany.
J Biomed Mater Res A. 2007 Dec 15;83(4):1184-1191. doi: 10.1002/jbm.a.31444.
Nitrogen containing bisphosphonates such as zoledronic acid (ZOL) are clinically used to prevent osteoclast induced bone loss. Previous studies indicated that bisphosphonates prevent osteoclast formation, decreases their resorption activity and lead to osteoclast apoptosis. Aim of the study was to investigate the effect of ZOL on fusion and resorption activity of osteoclast like cells (OLC) derived from human peripheral blood mononuclear cells (PBMNC) in vitro. For application of ZOL a local drug delivery system based on a coating for medical devices was used. ZOL was incorporated in the coating based on Poly(D,L-Lactide) (PDLLA) in different concentrations (10-50 microM). Control groups were treated without ZOL or ZOL pure substance in corresponding concentrations. Human PBMNCs were isolated and stimulated to form OLCs. After an experimental period of 144 h, TRAP staining of polynucleated cells was performed and TRAP positive cells were counted. A pit formation assay was performed and resorption lacunas on dentin chips were counted. Results showed a significant dose dependent decrease in the number of TRAP positive cells after exposure to ZOL incorporated in the drug delivery system or applied as pure substance. The amount of resorption lacunas was also dose dependent decreased using both application methods. In conclusion, exposure to specific concentrations of ZOL incorporated in a drug delivery system showed a significant decrease in OLC formation and activity comparable to the effect of pure substance. The effect on osteoclasts might be of clinical benefit to reduce orthopedic implant loosening and to support fracture healing.
含氮双膦酸盐如唑来膦酸（ZOL）在临床上用于预防破骨细胞诱导的骨质流失。先前的研究表明，双膦酸盐可阻止破骨细胞形成，降低其吸收活性并导致破骨细胞凋亡。本研究的目的是在体外研究ZOL对源自人外周血单个核细胞（PBMNC）的破骨样细胞（OLC）融合及吸收活性的影响。为应用ZOL，使用了一种基于医疗器械涂层的局部给药系统。ZOL以不同浓度（10 - 50 microM）掺入基于聚（D，L-丙交酯）（PDLLA）的涂层中。对照组分别用不含ZOL或相应浓度的ZOL纯物质进行处理。分离出人PBMNC并刺激其形成OLC。在144小时的实验期后，对多核细胞进行抗酒石酸酸性磷酸酶（TRAP）染色并计数TRAP阳性细胞。进行凹坑形成试验并计数牙本质芯片上的吸收陷窝。结果显示，暴露于掺入给药系统或作为纯物质应用的ZOL后，TRAP阳性细胞数量呈显著的剂量依赖性减少。两种应用方法均使吸收陷窝的数量呈剂量依赖性减少。总之，暴露于掺入给药系统的特定浓度ZOL显示OLC形成和活性显著降低，与纯物质的效果相当。对破骨细胞的作用可能在临床上有助于减少骨科植入物松动并促进骨折愈合。
