Bisphosphonates, Old Friends of Bones and New Trends in Clinics.

Bisphosphonates, used for a long time in osteoporosis management, are currently the target of intensive research, from pre-formulation studies to more advanced stages of clinical practice. This review presents an overview of the contributions of this family of compounds to human health, starting with the chemistry and clinical uses of bisphosphonates. Following this, their pharmacology is described, highlighting administration-borne handicaps and undesirable effects. The last three sections of the review describe the research efforts that seek to curb delivery-related issues and expand bisphosphonate use. Innovative routes and strategies of administration, such as nano-encapsulation for oral intake or injectable cements for local or in-bone delivery are presented, as well as the latest results of case studies or preclinical studies proposing new therapeutic indications for the clinically approved bisphosphonates. Finally, a selection of anti-infectious bisphosphonate new drug candidates is shown, with focus on the molecules reported in the last two decades.