Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, The Oxford University Institute of Musculoskeletal Sciences, Oxford, UK.
J Biomed Mater Res B Appl Biomater. 2010 Jan;92(1):149-55. doi: 10.1002/jbm.b.31500.
Bisphosphonates (BPs) inhibit bone resorption and are widely used for the treatment of bone diseases, including osteoporosis. BPs are also being studied for their effects on hydroxyapatite (HAP)-containing biomaterials. There is a growing appreciation that there are hitherto unexpected differences among BPs in their mineral binding affinities that affect their pharmacological and biological properties. To study these differences, we have developed a method based on fast performance liquid chromatography using columns of HAP to which BPs and other phosphate-containing compounds can adsorb and be eluted by using phosphate buffer gradients at pH 6.8. The individual compounds emerge as discrete and reproducible peaks for a range of compounds with different affinities. For example, the peak retention times (min; mean +/- SEM) were 22.0 +/- 0.3 for zoledronate, 16.16 +/- 0.44 for risedronate, and 9.0 +/- 0.28 for its phosphonocarboxylate analog, NE10790. These results suggest that there are substantial differences among BPs in their binding to HAP. These differences may be exploited in the development of biomaterials and may also partly explain the extent of their relative skeletal retention and persistence of biological effects observed in both animal and clinical studies.
双膦酸盐（BPs）抑制骨吸收，广泛用于治疗骨疾病，包括骨质疏松症。BPs 也因其对含羟磷灰石（HAP）的生物材料的影响而受到研究。人们越来越认识到，BPs 在其与矿物质的结合亲和力方面存在迄今为止尚未预料到的差异，这些差异影响其药理学和生物学特性。为了研究这些差异，我们开发了一种基于快速高效液相色谱的方法，使用 HAP 柱，BPs 和其他含磷酸盐的化合物可以吸附在这些柱上，并通过在 pH6.8 的磷酸盐缓冲梯度中洗脱。对于具有不同亲和力的一系列化合物，各个化合物都呈现出离散且可重现的峰。例如，唑来膦酸盐的峰保留时间（分钟；平均值 +/- SEM）为 22.0 +/- 0.3，利塞膦酸盐为 16.16 +/- 0.44，其膦羧酸酯类似物 NE10790 为 9.0 +/- 0.28。这些结果表明，BPs 在与 HAP 的结合方面存在显著差异。这些差异可用于生物材料的开发，也可部分解释在动物和临床研究中观察到的相对骨骼保留和生物效应持续时间的差异。
