Biology and management of myeloma-related bone disease |
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| Affiliation: | 1. Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece;2. Experimental Hematooncology Department, Medical University of Lublin, Poland;3. Department of Hematooncology and Bone Marrow Trasplantation, Medical University of Lublin, Poland;4. Polish Myeloma Consortium, Poznan, Poland;1. Department of Criminology, University of Leicester, 154 Upper New Walk, Leicester LE1 7QA, United Kingdom;2. Centre for Public Health, Liverpool John Moores University, Henry Cotton Campus, 15-21 Webster Street, Liverpool L3 2ET, United Kingdom;1. TOS Department, Ural Federal University named after the first President of Russia B. N. Yeltsin, 19 Mira str., 620002 Ekaterinburg, Russia;2. I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Science, 20 S. Kovalevskaya str., 620990 Ekaterinburg, Russia;3. Medicinal University of Vienna, Gert Lubec Proteomics Laboratory, 14 Lazarettgasse, 1090 Vienna, Austria;4. Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, 29071 Malaga, Spain;1. Department of Disease Control, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK;2. Parasitology Department, Indonesian Research Centre for Veterinary Science (Balai Besar Penelitian Veteriner), Bogor, Indonesia;3. Life Sciences Department, Natural History Museum, London SW7 5BD, UK;4. School of Forest Resources and Conservation, University of Florida, Gainesville, FL 32611, USA |
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| Abstract: | Bone disease is one of the most common complications of multiple myeloma. It is the result of increased osteoclast activity which is not compensated by osteoblast activity and leads to osteolytic lesions characterized by bone pain and increased risk for pathological fracture, spinal cord compression and need for radiotherapy or surgery to the bone. Recent studies have revealed novel pathways and molecules that are involved in the biology of myeloma bone disease including the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin pathway, the Wnt signaling inhibitors dickkopf-1 and sclerostin, macrophage inflammatory proteins, activin A, and others. A thorough study of these pathways have provided novel agents that may play a critical role in the management of myeloma related bone disease in the near future, such as denosumab (anti-RANKL), sotatercept (activin A antagonist), romosozumab (anti-sclerostin) or BHQ-880 (anti-dickkopf 1). Currently, bisphosphonates are the cornerstone in the treatment of myeloma related bone disease. Zoledronic acid and pamidronate are used in this setting with very good results in reducing skeletal-related events, but they cannot be used in patients with severe renal impairment. Furthermore, they have some rare but serious adverse events including osteonecrosis of the jaw and acute renal insufficiency. This review paper focuses on the latest advances in the pathophysiology of myeloma bone disease and in the current and future treatment options for its management. |
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| Keywords: | Multiple myeloma RANKL Bisphosphonates Zoledronic acid Denosumab |
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