Advances in the biology and treatment of myeloma bone disease.
The major clinical manifestations of multiple myeloma are related to the loss of bone. This bone loss often leads to pathologic fractures, spinal cord compression, hypercalcemia, and bone pain. This article reviews the cytokine network involved in myeloma bone disease; describes the signaling cascade involved in osteoclastogenesis and mechanisms of action of novel therapeutic options for myeloma bone disease such as osteoprotegerin, RANK human immunoglobulin fusion protein, the proteasome inhibitor PS-341, and bisphosphonates; and summarizes the latest clinical trial results using oral and intravenous bisphosphonates for bone disease in multiple myeloma.
Berenson
James R
JR
Multiple Myeloma and Bone Metastasis Program, Cedars-Sinai Medical Center, University of California Las Angeles School of Medicine, 8700 Beverly Boulevard, Bev. Mod. 1, Room 100, Los Angeles, CA 90402, USA.
D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002352:Carrier Proteins / Q000502:physiology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000502:physiology; D004164:Diphosphonates / Q000627:therapeutic use*; D016228:Endothelial Growth Factors / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007141:Immunoglobulin Fc Fragments; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000503:physiopathology*; D053244:Osteoprotegerin; D000077268:Pamidronate; D011719:Pyrazines / Q000627:therapeutic use; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077211:Zoledronic Acid
D001897:Boronic Acids; D002352:Carrier Proteins; D016207:Cytokines; D004164:Diphosphonates; D016228:Endothelial Growth Factors; D006023:Glycoproteins; D007093:Imidazoles; D007141:Immunoglobulin Fc Fragments; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D011719:Pyrazines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000069286:Bortezomib; D000077211:Zoledronic Acid; D000077268:Pamidronate