title: Therapeutic approaches to myeloma bone disease: an evolving story.
abstract: Bone disease is a major morbidity factor in patients with multiple myeloma and significantly affects their overall survival. A complex interplay between malignant plasma cells and other marrow cells results in the generation of a microenvironment capable of enhancing both tumor growth and bone destruction. Bisphosphonates have consistently reduced the incidence of skeletal-related events in patients with multiple myeloma and other osteotropic tumors as well. However, their use is burdened with side-effects, including the risks of osteonecrosis of the jaw and kidney failure, suggesting that they should be discontinued after prolonged administration. New molecular targets of cell cross-talk in myeloma bone marrow are therefore under intensive investigation and new drugs are being explored in preclinical and clinical studies of myeloma bone disease. Compounds targeting osteoclast activation pathways, such as receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin, B-cell activating factor, mitogen-activated protein kinase and macrophage inflammatory protein-1α/chemokine receptor for macrophage inflammatory protein-1α axes, or soluble agents that improve osteoblast differentiation by modulating specific inhibitors such as Dickkopf-1 and transforming growth factor-β, as well as novel approaches of cytotherapy represent a new generation of promising drugs for the treatment of myeloma bone disease.
authors.affiliation: DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari 'Aldo Moro', Piazza Giulio Cesare, 11 - 70124 Bari, Italy. vito.longo79@tiscali.it
authors.forename: Vito
authors.initials: V
authors.lastname: Longo
authors.forename: Oronzo
authors.initials: O
authors.lastname: Brunetti
authors.forename: Stella
authors.initials: S
authors.lastname: D'Oronzo
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology*; D002454:Cell Differentiation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates