title: Bone-resorbing cells in multiple myeloma: osteoclasts, myeloma cell polykaryons, or both?
abstract: Myeloma bone disease (MBD) leads to progressive destruction of the skeleton and is the most severe cause of morbidity in multiple myeloma. Its pathogenetic mechanisms are not fully understood, though the current evidence points to osteoclast (OC) hyperactivity coupled with defective osteoblast function unable to counteract bone resorption. OCs are generated in bone marrow by myeloid progenitors through increased levels of receptor activator of nuclear factor kappaB ligand and M-CSF, whose intracellular pathways propagate signals that activate sequential transcription factors, resulting in the production of major OC enzymes that drive specific functions such as acidification and degradation of the bone matrix. Osteolytic lesions, however, are not characterized by massive OC content, whereas malignant plasma cells, which are usually present in a high number, may occur as large multinucleated cells. The possibility that myeloma cells fuse and generate polykaryons in vivo is suggested by the in vitro formation of multinuclear cells that express tartrate-resistant acid phosphatase and produce pits and erosive lacunae on experimental osteologic substrates. Further, the detection in vivo of polykaryons with chromosome translocations typical of myeloma cells lends support to the view that myeloma polykaryons may act as functional OCs and participate in the skeletal destruction by resorbing bone.
authors.affiliation: DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Bari, Italy. f.silvestris@dimo.uniba.it
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
authors.forename: Sabino
authors.initials: S
authors.lastname: Ciavarella
authors.forename: Monica
authors.initials: M
authors.lastname: De Matteo
authors.forename: Marco
authors.initials: M
authors.lastname: Tucci
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
mesh_terms: D001862:Bone Resorption / Q000473:pathology*; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology*; D010950:Plasma Cells / Q000473:pathology*