Interactions between Clinically Used Bisphosphonates and Bone Mineral: from Coordination Chemistry to Biomedical Applications and Beyond

Abstract 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 2+ coordination chemistry through to interactions with hydroxyapatite, nanocrystalline apatites, and natural bone mineral.