Henneman Zachary J, Nancollas George H, Ebetino F Hal, Russell R Graham G, Phipps Roger J
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.
J Biomed Mater Res A. 2008 Jun 15;85(4):993-1000. doi: 10.1002/jbm.a.31599.
Bisphosphonates (BPs), which display a high affinity for calcium phosphate surfaces, are able to selectively target bone mineral, where they are potent inhibitors of osteoclast-mediated bone resorption. The dissolution of synthetic hydroxyapatite (HAP) has been used previously as a model for BP effects on natural bone mineral. The present work examines the influence of BPs on carbonated apatite (CAP), which mimics natural bone more closely than does HAP. Constant composition dissolution experiments were performed at pH 5.50, physiological ionic strength (0.15M) and temperature (37 degrees C). Selected BPs were added at (0.5 x 10(-6)) to (50.0 x 10(-6))M, and adsorption affinity constants, K(L), were calculated from the kinetics data. The BPs showed concentration-dependent inhibition of CAP dissolution, with significant differences in rank order zoledronate > alendronate > risedronate. In contrast, for HAP dissolution at pH 5.50, the differences between the individual BPs were considerably smaller. The extent of CAP dissolution was also dependent on the relative undersaturation, sigma, and CAP dissolution rates increased with increasing carbonate content. These results demonstrate the importance of the presence of carbonate in mediating the dissolution of CAP, and the possible involvement of bone mineral carbonate in observed differences in bone affinities of BPs in clinical use.
双膦酸盐（BPs）对磷酸钙表面具有高亲和力，能够选择性地靶向骨矿物质，在那里它们是破骨细胞介导的骨吸收的有效抑制剂。合成羟基磷灰石（HAP）的溶解先前已被用作BPs对天然骨矿物质作用的模型。本研究考察了BPs对碳酸磷灰石（CAP）的影响，碳酸磷灰石比HAP更接近地模拟天然骨。在pH 5.50、生理离子强度（0.15M）和温度（37℃）下进行了恒定组成溶解实验。以（0.5×10⁻⁶）至（50.0×10⁻⁶）M添加选定的BPs，并根据动力学数据计算吸附亲和常数K(L)。BPs对CAP溶解表现出浓度依赖性抑制，唑来膦酸盐>阿仑膦酸盐>利塞膦酸盐的排名顺序存在显著差异。相比之下，对于pH 5.50下的HAP溶解，各个BPs之间的差异要小得多。CAP溶解程度还取决于相对不饱和程度σ，并且CAP溶解速率随碳酸盐含量增加而增加。这些结果证明了碳酸盐的存在对介导CAP溶解的重要性，以及骨矿物质碳酸盐可能参与临床使用中观察到的BPs骨亲和力差异。
