title: The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease.
abstract: Owing to the common coincidence of osteoporosis and vascular disease, pathophysiological links between both disorders have long been sought. The osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK)/receptor activator of NF-kappaB ligand (RANKL) cytokine network, a key regulatory system in bone homeostasis, has been implicated recently in vascular calcification, changes in matrix composition and diabetic macroangiopathy, aortic aneurysm development, heart failure and, most importantly, advanced atherosclerosis, plaque destabilization and manifestation of cardiovascular diseases. The concept of an active role of RANKL and OPG in vascular pathophysiology is intriguing and is gaining increasing support from both epidemiological and basic research. OPG serum level is considered to be a stable and reliable indicator of the overall activity of the OPG/RANK/RANKL axis and may find application as a biomarker of vascular risk and prognosis. RANKL in turn may be a suitable target for novel therapies. Pharmacological strategies for specific interference with the OPG/RANK/RANKL axis are currently being developed and evaluated in osteoporosis therapy.
authors.affiliation: Medical University Innsbruck, Department of Neurology, Anichstr. 35, A-6020 Innsbruck, Austria. Stefan.Kiechl@i-med.ac.at
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.forename: Philipp
authors.initials: P
authors.lastname: Werner
authors.forename: Michael
authors.initials: M
authors.lastname: Knoflach
authors.forename: Martin
authors.initials: M
authors.lastname: Furtner
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D014652:Vascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B