Pathogenesis of myeloma bone disease.
Bone disease in multiple myeloma (MM) is characterized by lytic bone lesions, which can cause severe bone pain, pathologic fractures and hypercalcemia. However, the lytic bone disease in MM differs from that in other cancer patients who have lytic bone metastases. Although increased osteoclastic bone destruction is involved in MM and other tumors involving bone, in contrast to other tumors, once the MM tumor burden exceeds 50% in a local area, osteoblast activity is either suppressed or absent. The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation has been a topic of intensive investigation over the last several years and will be reviewed in this article.
Roodman
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Veterans Affairs Pittsburgh Healthcare System, Department of Medicine/Hematology-Oncology, University of Pittsburgh, Pittsburgh, PA 15240, USA. roodmangd@upmc.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002448:Cell Adhesion; D016207:Cytokines / Q000378:metabolism; D000069448:Denosumab; D005598:Fractures, Spontaneous / Q000209:etiology / Q000503:physiopathology; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000503:physiopathology; D007155:Immunologic Factors / Q000627:therapeutic use; D007378:Interleukins / Q000502:physiology; D009101:Multiple Myeloma / Q000150:complications* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000502:physiology; D010014:Osteolysis / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D011719:Pyrazines / Q000627:therapeutic use; D053245:RANK Ligand / Q000627:therapeutic use; D017154:Stromal Cells / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001897:Boronic Acids; D016207:Cytokines; D005938:Glucocorticoids; D007155:Immunologic Factors; D007378:Interleukins; D009363:Neoplasm Proteins; D011719:Pyrazines; D053245:RANK Ligand; D051153:Wnt Proteins; D000069448:Denosumab; D000069286:Bortezomib