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This article is part of the supplement: Basic science, rationale, background and future of denosumab: a RANK ligand inhibitor

Open Badges Review

Multiple myeloma/hypercalcemia

Babatunde O Oyajobi

Author affiliations

University of Texas Health Science Center at San Antonio, Department of Cellular and Structural Biology (MSC 7762), Floyd Curl Drive, San Antonio, Texas 78229-3900, USA

Citation and License

Arthritis Research & Therapy 2007, 9(Suppl 1):S4  doi:10.1186/ar2168

Published: 29 June 2007


Multiple myeloma, a cancer of plasma cells, is associated with excessive tumor-induced, osteoclast-mediated bone destruction. Hypercalcemia remains the most frequent metabolic complication of myeloma in patients, and excessive osteolysis plays a major contributory role in its pathogenesis. The clinical presentation of hypercalcemia in patients varies depending on the level of ionized calcium; it can be life threatening, as in the case of hypercalcemic crisis, requiring immediate medical treatment to prevent death. During the past few years there have been exciting developments in our understanding of the pathogenesis of myeloma bone disease; in particular, key mediators of the osteoclastic bone resorption in myeloma have been identified, including receptor activator of nuclear factor-κB ligand (RANKL) and macrophage inflammatory protein-1α. There is also increasing evidence that Dickkopf 1, which has been shown to be over-expressed in myeloma patients, is also a potent stimulator of osteoclast formation and activity. Importantly, the available data suggest that RANKL is the final common mediator of osteoclastic bone resorption, irrespective of the upstream initiator molecule. This brief review presents an overview of the roles played by these mediators in inducing osteolysis in myeloma bone disease, and it discusses targeting RANKL as a potential new treatment strategy in myeloma bone disease and myeloma-associated hypercalcemia.