title: Myeloma bone disease: pathogenetic mechanisms and clinical assessment.
abstract: Bone disease in multiple myeloma (MM) leads to progressive devastation of the skeleton and is the most severe cause of morbidity. Its pathogenetic mechanisms are not fully defined, though the current evidence points to hyperactivation of osteoclasts (OC) in presence of a major defect of bone repairing in erosion sites due to osteoblast (OB) impairment. Bone resorption, however, is promoted by early OB, namely stromal cells that respond to chronic stimulation by myeloma cells by enhancing marrow levels of RANKL and other osteoclastogenic factors and thus accelerating the maturation of OC progenitors. In myeloma bone disease (MBD), OBs are systematically defeated by a number of inhibiting effects induced by the malignant clone within the marrow microenvironment. Thus, MBD primarily affects the OB lineage, particularly in overt MM, where serum markers of osteoblastogenesis, such as osteocalcin and osteoprotegerin, are extremely low in contrast with their slight increase in inactive MM. These markers, in association with others of bone turnover (RANKL, MIP-1alpha, type I collagen telopeptides such as NTX and CTX) may be used in the clinical assessment of MBD as well as to monitor the efficacy of bisphosphonate in delaying the progressive skeletal destruction.
authors.affiliation: Department of Internal Medicine and Clinical Oncology (DIMO), University of Bari, P.za Giulio Cesare, 11-70124 Bari, Italy. f.silvestris@dimo.uniba.it
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
authors.forename: Lucia
authors.initials: L
authors.lastname: Lombardi
authors.forename: Monica
authors.initials: M
authors.lastname: De Matteo
authors.forename: Arianna
authors.initials: A
authors.lastname: Bruno
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
mesh_terms: D001847:Bone Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology