This Article Full Text (PDF) All Versions of this Article: theoncologist.2008-0087v1 14/3/264    most recent eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Silvestris, F. Articles by Dammacco, F. Search for Related Content PubMed PubMed Citation Articles by Silvestris, F. Articles by Dammacco, F.

Bone-Resorbing Cells in Multiple Myeloma: Osteoclasts, Myeloma Cell Polykaryons, or Both?

DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Bari, Italy

Key Words. Multiple myeloma • Myeloma bone disease • Osteoclasts • Polykaryons

Correspondence: Correspondence: Franco Silvestris, M.D., DIMO, P.za Giulio Cesare, 11, 70124 – Bari, Italy. Telephone: 3980-5478771; Fax: 3980-5478831; e-mail: f.silvestris{at}dimo.uniba.it

Received April 8, 2008; accepted for publication September 3, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

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 B 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.

This article has been cited by other articles:

				O. Sezer Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment Oncologist, March 1, 2009; 14(3): 276 - 283. [Abstract] [Full Text] [PDF]