Clinical and translational pharmacology of bisphosphonates

The year 2019 marks 50 years since the first publications on the biological effects of bisphosphonates (BPs). These agents have served for the past several decades as the pharmacological cornerstone for the treatment of skeletal disorders such as Paget’s disease of bone, osteoporosis and cancers metastatic to bone. The early discovery and clinical development of BPs has been reviewed elsewhere. Abundant preclinical, translational and clinical research with BPs has led to a wealth of data that now enable us to rationally prescribe these drugs to the right patients using tailored dosing regimens to provide an optimal balance between efficacy and side effects. Better insight into the precise effects of BPs on various bone cell populations has resulted in continued efforts to develop new BPs for the treatment of metabolic bone diseases, while non-skeletal-related indications for these drugs have been more recently explored. In addition, BPs are currently under investigation as agents for the targeting of other drugs, such as antibiotics, to bone tissue. This chapter provides an overview of our current knowledge on the (pre-) clinical and translational pharmacology of BPs, and illustrates how this knowledge has been used both for the development of new compounds and for the treatment of patients.