Why do myeloma patients have bone disease? A historical perspective.

Published on May 1, 2020in Blood Reviews6.125
· DOI :10.1016/J.BLRE.2019.100646
Magne Børset32
Estimated H-index: 32
(NTNU: Norwegian University of Science and Technology),
Anders Sundan33
Estimated H-index: 33
(NTNU: Norwegian University of Science and Technology)
+ 1 AuthorsTherese Standal16
Estimated H-index: 16
(NTNU: Norwegian University of Science and Technology)
Abstract The question of how myeloma cells cause destruction of skeletal tissue has interested scientists for many years, and knowledge in this field has developed in parallel with the understanding of physiological bone remodeling. The identification of bioactive proteins of the cytokine class during the last decades of the previous century and mapping of their role in the regulation of anabolic and catabolic processes in bone, led to a sequence of hypotheses about how the same peptides also could be involved in myeloma-driven bone destruction. Although bone remodeling is now understood in detail, there is still no clear unified theory of how myeloma cells degrade bone. The reason for this could be that there is no single mechanism that is active in every patient. The common trait is possibly that myeloma cells benefit from bone destruction per se, and the strategy they use to accomplish this vary between patients.
  • References (115)
  • Citations (1)
📖 Papers frequently viewed together
25 Citations
5 Citations
44 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Jens HillengassH-Index: 33
#2Saad Z. Usmani (Carolinas Healthcare System)H-Index: 35
Last. Suzanne Lentzsch (Columbia University)H-Index: 27
view all 35 authors...
Summary Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is crucial in the investigation of multiple myeloma and often dictates the decision to start treatment. Furthermore, detection of minimal residual disease is important for prognosis determination and treatment planning, and it has underscored an unmet need for sensitive imaging methods that accurately assess patient response to ...
3 CitationsSource
#1Niroshani S. Soysa (University of Peradeniya)H-Index: 14
#2Neil Alles (University of Peradeniya)H-Index: 14
: In the recent past, there has been a burgeoning interest in targeting cytokines such as IL-3 for specific disease conditions of bone such as rheumatoid arthritis and multiple myeloma. Unlike other cytokines, IL-3 is a cytokine with a multilineage potential and broad spectrum of target cells and it plays a vital role in hematopoiesis. Due to its common receptor subunit, the action of IL-3 shows functional redundancy with other cytokines such as the granulocyte-macrophage colony-stimulating fact...
1 CitationsSource
#1Zejian Zhang (LUMC: Leiden University Medical Center)H-Index: 2
#2Marita Westhrin (NTNU: Norwegian University of Science and Technology)H-Index: 5
Last. Stephanie Holst (LUMC: Leiden University Medical Center)H-Index: 11
view all 6 authors...
Abstract Background Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features. Methods Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samp...
2 CitationsSource
#1Wei Feng (SDU: Shandong University)H-Index: 9
#2Jie Guo (SDU: Shandong University)H-Index: 7
Last. Minqi Li (SDU: Shandong University)H-Index: 24
view all 3 authors...
Abstract Osteoclasts are functional cells required for bone resorption. They are derived from hematopoietic precursors and undergo a series of differentiation and fusion steps in response to various humoral factors. Depending on the importance in osteoclastogenesis, the pathways for the differentiation of hematopoietic precursors to mature osteoclasts can be divided into two categories: canonical and the non-canonical. Receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast for...
1 CitationsSource
#1Sylvia Faict (Vrije Universiteit Brussel)H-Index: 5
#2Joséphine Muller (University of Liège)H-Index: 7
Last. Eline Menu (Vrije Universiteit Brussel)H-Index: 32
view all 12 authors...
Progression of multiple myeloma (MM) is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles takes place. This cross-talk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. In this paper, we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine ...
9 CitationsSource
#1Qian-Yuan Wu (Nantong University)H-Index: 2
#2Xia Li (Nantong University)H-Index: 11
Last. Feng Lai Yuan (Nantong University)H-Index: 3
view all 10 authors...
Osteoporosis is a “a metabolic bone disease” disease characterized by a decrease in bone mass and degradation of the bone microstructure, which increases bone fragility and fracture risk. However, the molecular mechanisms of osteoporosis remain unclear. Long non-coding RNAs (lncRNAs) have become important epigenetic regulators controlling the expression of genes and affecting multiple biological processes. Accumulating evidence of the involvement of lncRNAs in bone remolding has increased unders...
3 CitationsSource
#1Shokichi Tsukamoto (Harvard University)H-Index: 4
#2Marianne B. Løvendorf (Harvard University)H-Index: 1
Last. Irene M. Ghobrial (Harvard University)H-Index: 67
view all 20 authors...
Myeloma bone disease is a devastating complication of multiple myeloma (MM) and is caused by dysregulation of bone remodeling processes in the bone marrow microenvironment. Previous studies showed that microRNA-138 (miR-138) is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and that inhibiting its function enhances bone formation in vitro. In this study, we explored the role of miR-138 in myeloma bone disease and evaluated the potential of systemically del...
2 CitationsSource
#1Bingzong Li (Soochow University (Suzhou))H-Index: 3
#2Hongxia Xu (Soochow University (Suzhou))H-Index: 3
Last. Wenzhuo Zhuang (Soochow University (Suzhou))H-Index: 4
view all 12 authors...
Multiple myeloma (MM) is characterized by the decreased osteogenic potential of mesenchymal stem cells (MSCs). Communication between cancer cells and cancer stromal cells is a driving factor in tumor progression. Understanding the myeloma–stroma interactions is critical to the development of effective strategies that can reverse bone diseases. Here we identified that bioactive lncRNA RUNX2-AS1 in myeloma cells could be packed into exosomes and transmitted to MSCs, thus repressing the osteogenesi...
17 CitationsSource
#1Yujiao Han (CAS: Chinese Academy of Sciences)H-Index: 2
#2Xiuling You (CAS: Chinese Academy of Sciences)H-Index: 1
Last. Weiguozou (CAS: Chinese Academy of Sciences)H-Index: 25
view all 5 authors...
The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes, and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin (SOS...
30 CitationsSource
#1Noopur Raje (Harvard University)H-Index: 71
#2Evangelos Terpos (UoA: National and Kapodistrian University of Athens)H-Index: 48
Last. G. David Roodman (IU: Indiana University)H-Index: 58
view all 13 authors...
Summary Background Multiple myeloma is characterised by monoclonal paraprotein production and osteolytic lesions, commonly leading to skeletal-related events (spinal cord compression, pathological fracture, or surgery or radiotherapy to affected bone). Denosumab, a monoclonal antibody targeting RANKL, reduces skeletal-related events associated with bone lesions or metastases in patients with advanced solid tumours. This study aimed to assess the efficacy and safety of denosumab compared with zol...
50 CitationsSource
Cited By1
#1Pawel Robak (Medical University of Łódź)H-Index: 14
Last. Wojciech Fendler (Medical University of Łódź)H-Index: 22
view all 12 authors...
The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bo...