TITLE:
Biology and Treatment of Skeletal Manifestations in Multiple Myeloma
AUTHORS:
Nikolaos A. Stavropoulos, Argyro Papadoyiannis, Dimitris Maltezas, Petros Stavrou, George C. Babis, Panayiotis J. Papagelopoulos, Gerasimos A. Pangalis, Marie-Christine Kyrtsonis
KEYWORDS:
Multiple Myeloma, Skeletal Manifestations, Biology, Treatment
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.4,
April
22,
2014
ABSTRACT: MM is frequently associated with the development of osteolytic bone lesions, osteoporosis and pathological fractures. Bone destruction in MM is caused by osteoclasts recruited in areas adjacent to myeloma plasma cells; their contact triggers both cell types to secrete soluble factors sustaining one each other’s activation and proliferation. Osteoclasts differentiate and maturate upon binding of the receptor activator of NF-kappaB ligand (RANKL), secreted by bone marrow microenvironmental cells, to its receptor (RANK) on osteoclast progenitors, while osteoprotegerin (OPG), a natural decoy receptor, can block the aforementioned ligation. At the same time osteoblasts are inactivated by the Wnt/β-catenin signaling pathway inhibitor, Dickkopf-1 protein (DKK-1), secreted by malignant plasma cells. Furthermore, DKK-1 deregulates the OPG/RANKL equilibrium, promoting osteoclastogenesis. Myeloma bone disease (MBD) can be treated with myeloma-directed chemotherapy and agents inhibiting bone resorption such as aminobisphosphonates, although new promising biology driven monoclonal antibodies targeting osteoclastogenesis mechanisms are emerging. Palliative MBD treatment includes analgesics, orthotics, radiation therapy, vertebroplasty and kyphoplasty. In case of spinal cord compression, radiation therapy or surgical decompression, should be instantly performed, along with steroid administration. Surgery may also be an option especially in case of weight-bearing bone fractures. MBD is a morbid complication and should be carefully managed because it deteriorates patients’ quality of life and worsens disease outcome.