Pharmacology of bisphosphonates.

Four decades of preclinical and clinical research of the pharmacology of bisphosphonates have generated data and concepts that have considerably improved their clinical use. However, despite this progress several pharmacological aspects relevant to bisphosphonate action on bone are still incompletely understood. This is mainly due to the complex, unique pharmacological properties of bisphosphonates. We review here the pharmacokinetic and pharmacodynamic data of bisphosphonates that are relevant for their clinical application and for the potential choice of a given compound, focusing on uncertainties that still exist.