TY - JOUR TI - Extra-skeletal effects of bisphosphonates AU - Panagiotakou, A. AU - Yavropoulou, M. AU - Nasiri-Ansari, N. AU - Makras, P. AU - Basdra, E.K. AU - Papavassiliou, A.G. AU - Kassi, E.N. JO - Metabolism: Clinical and Experimental PY - 2020 VL - 110 TODO - null SP - null PB - W.B. Saunders SN - 0026-0495 TODO - 10.1016/j.metabol.2020.154264 TODO - bisphosphonic acid derivative; glucose; hydrogel; liposome; nanoparticle; bisphosphonic acid derivative, cardiovascular disease; drug delivery system; eye disease; glucose homeostasis; human; immune system; malignant neoplasm; meta analysis (topic); neurologic disease; non insulin dependent diabetes mellitus; nonhuman; pathophysiology; priority journal; randomized controlled trial (topic); Review; animal; cardiovascular system; clinical trial (topic); drug effect; eye; non insulin dependent diabetes mellitus, Animals; Cardiovascular System; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diphosphonates; Eye; Humans; Immune System TODO - Background: Bisphosphonates (BPs) are pyrophosphate analogues widely used in diseases related to bone loss and increased bone turnover. Their high affinity for bone hydroxyapatite makes them ideal agents for bone diseases, while preventing them from reaching other cells and tissues. Data of the last decade, however, have demonstrated extra-skeletal tissue deposition and a variety of non-skeletal effects have been recently recognized. As such, BPs have been shown to exert anti-tumor, immunomodulatory, anti-inflammatory and anti-diabetic effects. In addition, new delivery systems (liposomes, nanoparticles, hydrogels) are being developed in an effort to expand BPs clinical application to extra-skeletal tissues and enhance their overall therapeutic spectrum and effectiveness. In the present review, we outline current data on extra-skeletal actions of bisphosphonates and attempt to unravel the underlying pathophysiological mechanisms. © 2020 Elsevier Inc. ER -