Department of Inorganic Chemistry, Wrocław Medical University, Borowska 211A, 50-556, Wrocław, Poland.
ChemMedChem. 2018 Feb 20;13(4):289-302. doi: 10.1002/cmdc.201700769. Epub 2018 Jan 30.
Bisphosphonates (BPs) are well-established, widely used first-choice drugs for bone-related diseases and are one of the few classes of molecules for selective bone targeting. Their binding to calcium cations within hydroxyapatite (HA) is a key physicochemical event that takes place on the bone surface. It is the starting point for a cascade of biochemical reactions and cellular effects that lead to the pharmacological activity of BPs. The phenomenon has been known for years, yet its physicochemical nature is still not fully understood. In particular, the adsorption/release processes and structure-function relationships of BPs remain to be clarified. These are elementary, yet crucial factors, which should influence the design and development of new delivery tools or drugs with improved characteristics. This review summarizes the current understanding of the chemical interactions between clinically used BPs and bone mineral, starting from basic Ca coordination chemistry through to interactions with hydroxyapatite, nanocrystalline apatites, and natural bone mineral.
双膦酸盐（BPs）是一种成熟的、广泛应用的首选药物，用于治疗与骨骼相关的疾病，是少数几种具有选择性骨骼靶向的分子类别之一。BPs 与羟基磷灰石（HA）中钙离子的结合是在骨表面发生的关键物理化学事件。这是一系列生化反应和细胞效应的起点，导致 BPs 的药理活性。这一现象已经存在多年，但它的物理化学性质仍未被完全理解。特别是 BPs 的吸附/释放过程和结构-功能关系仍有待澄清。这些是基本但至关重要的因素，应该影响新的输送工具或具有改进特性的药物的设计和开发。本综述从基本的 Ca 配位化学到与羟基磷灰石、纳米晶磷灰石和天然骨矿物质的相互作用，总结了目前对临床应用的 BPs 与骨矿物质之间化学相互作用的理解。
