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 Ca²⁺ coordination chemistry through to interactions with hydroxyapatite, nanocrystalline apatites, and natural bone mineral.

中文翻译：

---

临床使用的双膦酸盐与骨矿物质之间的相互作用：从配位化学到生物医学应用及其他

双膦酸盐（BPs）是公认的，广泛使用的与骨相关疾病的首选药物，并且是针对骨靶向的少数几类分子之一。它们与羟基磷灰石（HA）中的钙阳离子结合是在骨表面发生的关键物理化学事件。这是导致BP药理活性的一系列生化反应和细胞作用的起点。这种现象已经知道了多年，但其理化性质仍未完全明了。特别是，BPs的吸附/释放过程和结构-功能关系尚待阐明。这些是基本但至关重要的因素，它们应影响具有改进特性的新型输送工具或药物的设计和开发。通过与羟基磷灰石，纳米晶磷灰石和天然骨矿物质的相互作用进行²⁺配位化学。