Advanced glycation end products play adverse proinflammatory activities in osteoporosis.
Osteoporosis is a major public health burden that is expected to further increase as the global population ages. In the last twenty years, advanced glycation end products (AGEs) have been shown to be critical mediators both in the pathogenesis and development of osteoporosis and other chronic degenerative diseases related to aging. The accumulation of AGEs within the bone induces the formation of covalent cross-links with collagen and other bone proteins which affects the mechanical properties of tissue and disturbs bone remodelling and deterioration, underlying osteoporosis. On the other hand, the gradual deterioration of the immune system during aging (defined as immunosenescence) is also characterized by the generation of a high level of oxidants and AGEs. The synthesis and accumulation of AGEs (both localized within the bone or in the systemic circulation) might trigger a vicious circle (in which inflammation and aging merged in the word "Inflammaging") which can establish and sustain the development of osteoporosis. This narrative review will update the molecular mechanisms/pathways by which AGEs induce the functional and structural bone impairment typical of osteoporosis.
Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
Roberta
0000-0002-3130-9372
R
Sanguineti
Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
Alessandra
0000-0002-9084-2636
A
Puddu
Division of Cardiology, Foundation for Medical Researches, Faculty of Medicine, Geneva University Hospitals, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
François
F
Mach
Division of Cardiology, Foundation for Medical Researches, Faculty of Medicine, Geneva University Hospitals, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland ; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 6 Viale Benedetto XV, 16132 Genoa, Italy ; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
Fabrizio
0000-0003-0823-8729
F
Montecucco
Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
Giorgio Luciano
GL
Viviani
D000375:Aging; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D004164:Diphosphonates / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D010024:Osteoporosis / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress
D015415:Biomarkers; D004164:Diphosphonates; D017127:Glycation End Products, Advanced; D016877:Oxidants