title: Bone: a new endocrine organ at the heart of chronic kidney disease and mineral and bone disorders.
abstract: Recent reports of several bone-derived substances, some of which have hormonal properties, have shed new light on the bone-cardiovascular axis. Deranged concentrations of humoral factors are not only epidemiologically connected to cardiovascular morbidity and mortality, but can also be causally implicated, especially in chronic kidney disease. FGF23 rises exponentially with advancing chronic kidney disease, seems to reach maladaptive concentrations, and then induces left ventricular hypertrophy, and is possibly implicated in the process of vessel calcification. Sclerostin and DKK1, both secreted mainly by osteocytes, are important Wnt inhibitors and as such can interfere with systems for biological signalling that operate in the vessel wall. Osteocalcin, produced by osteoblasts or released from mineralised bone, interferes with insulin concentrations and sensitivity, and its metabolism is disturbed in kidney disease. These bone-derived humoral factors might place the bone at the centre of cardiovascular disease associated with chronic kidney disease. Most importantly, factors that dictate the regulation of these substances in bone and subsequent secretion into the circulation have not been researched, and could provide entirely new avenues for therapeutic intervention.
authors.affiliation: Department of Nephrology and Institute for Cardiovascular Research VU, VU University Medical Center, Amsterdam, Netherlands. Electronic address: m.vervloet@vumc.nl.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.affiliation: Division of Nephrology, Ambroise Paré Hospital, Paris Ile de France Ouest University, Boulogne Billancourt, Paris, France; INSERM U1088, Picardie University Jules Verne, Amiens, France.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.affiliation: Department of Cardiology and Intensive Care Medicine, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Brandenburg
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Mazzaferro
authors.affiliation: Department of Health Sciences, Renal Division, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
authors.affiliation: Department of Nephrology and Dialysis, Clinique du Landy, Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ureña-Torres
authors.affiliation: Department of Nephrology, Fundació Puigvert, IIB Sant Pau, REDinREN, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bover
authors.affiliation: King's Health Partners, AHSC, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Goldsmith
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001847:Bone Diseases / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008903:Minerals / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; C000717427:FGF23 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D008903:Minerals; C422903:SOST protein, human; D015675:Osteocalcin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23