{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:45:15Z","timestamp":1790937915841,"version":"4.1.0"},"reference-count":156,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL\/RANK\/OPG axis, Notch signaling, the Wnt\/\u03b2-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD.<\/jats:p>","DOI":"10.3390\/ijms23063112","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T03:06:10Z","timestamp":1647313570000},"page":"3112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Pathogenesis and Treatment of Myeloma-Related Bone Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-112X","authenticated-orcid":false,"given":"Yuh-Ching","family":"Gau","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-2219","authenticated-orcid":false,"given":"Tsung-Jang","family":"Yeh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-6022","authenticated-orcid":false,"given":"Chin-Mu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Yien","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rutgers-Camden, Camden, NJ 08102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Hua","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/j.seminoncol.2016.11.004","article-title":"Multiple myeloma epidemiology and survival: A unique malignancy","volume":"43","author":"Kazandjian","year":"2016","journal-title":"Semin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.canep.2018.06.003","article-title":"Epidemiology of multiple myeloma in Taiwan, a population based study","volume":"55","author":"Tang","year":"2018","journal-title":"Cancer Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/ajh.24236","article-title":"Myeloma today: Disease definitions and treatment advances","volume":"91","author":"Rajkumar","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jbo.2013.04.001","article-title":"Myeloma bone disease: Pathophysiology and management","volume":"2","author":"Silbermann","year":"2013","journal-title":"J. Bone Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/leu.2010.62","article-title":"Prognostic variables for survival and skeletal complications in patients with multiple myeloma osteolytic bone disease","volume":"24","author":"Terpos","year":"2010","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/jcb.22403","article-title":"Pathogenesis of myeloma bone disease","volume":"109","author":"Roodman","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1182\/blood-2018-11-852459","article-title":"Myeloma bone disease: From biology findings to treatment approaches","volume":"133","author":"Terpos","year":"2019","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yen, C.-H., Hsu, C.-M., Hsiao, S.Y., and Hsiao, H.-H. (2020). Pathogenic mechanisms of myeloma bone disease and possible roles for nrf2. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186723"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/leu.2011.381","article-title":"Increased osteocyte death in multiple myeloma patients: Role in myeloma-induced osteoclast formation","volume":"26","author":"Giuliani","year":"2012","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.1016\/S1470-2045(20)30559-3","article-title":"Treatment of multiple myeloma-related bone disease: Recommendations from the Bone Working Group of the International Myeloma Working Group","volume":"22","author":"Terpos","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1365-2141.1982.tb03936.x","article-title":"Quantitative histology of myeloma-induced bone changes","volume":"52","author":"Charhon","year":"1982","journal-title":"Br. J. Haematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/345442a0","article-title":"The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene","volume":"345","author":"Yoshida","year":"1990","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1182\/blood-2002-09-2684","article-title":"RANK ligand and osteoprotegerin in myeloma bone disease","volume":"101","author":"Sezer","year":"2003","journal-title":"Blood"},{"key":"ref_17","first-page":"912","article-title":"Osteoprotegerin Is a Soluble Decoy Receptor for Tumor Necrosis Factor-related Apoptosis-inducing Ligand\/Apo2 Ligand and Can Function as a Paracrine Survival Factor for Human Myeloma Cells","volume":"63","author":"Shipman","year":"2003","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1182\/blood-2002-04-1190","article-title":"Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells","volume":"100","author":"Standal","year":"2002","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1182\/blood-2003-02-0380","article-title":"Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: Proposal for a novel prognostic index","volume":"102","author":"Terpos","year":"2003","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/leu.2008.336","article-title":"Pathogenesis of myeloma bone disease","volume":"23","author":"Roodman","year":"2009","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/leu.2013.6","article-title":"Notch-directed microenvironment reprogramming in myeloma: A single path to multiple outcomes","volume":"27","author":"Colombo","year":"2013","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"26826","DOI":"10.18632\/oncotarget.5025","article-title":"Notch signaling deregulation in multiple myeloma: A rational molecular target","volume":"6","author":"Colombo","year":"2015","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/leu.2013.27","article-title":"Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4\/SDF-1","volume":"27","author":"Mirandola","year":"2013","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5102","DOI":"10.1158\/0008-5472.CAN-21-0524","article-title":"Targeting Notch Inhibitors to the Myeloma Bone Marrow Niche Decreases Tumor Growth and Bone Destruction without Gut Toxicity","volume":"81","author":"Sabol","year":"2021","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1080\/10428190500175049","article-title":"Significance of macrophage inflammatory protein-1 alpha (MIP-1\u03b1) in multiple myeloma","volume":"46","author":"Terpos","year":"2005","journal-title":"Leuk. Lymphoma"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/leu.2011.43","article-title":"A novel role for CCL3 (MIP-1\u03b1) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function","volume":"25","author":"Vallet","year":"2011","journal-title":"Leukemia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1182\/blood-2006-04-017087","article-title":"MIP-1\u03b1 (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in multiple myeloma","volume":"108","author":"Trudel","year":"2006","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.3389\/fimmu.2019.02182","article-title":"Chemokines in Physiological and Pathological Bone Remodeling","volume":"10","author":"Brylka","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1182\/blood-2002-12-3905","article-title":"Dual effects of macrophage inflammatory protein-1\u03b1 on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease","volume":"102","author":"Oyajobi","year":"2003","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/leu.2015.259","article-title":"Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20","volume":"30","author":"Palma","year":"2016","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12935-014-0132-6","article-title":"Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease","volume":"14","author":"Fu","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1182\/blood-2007-05-093294","article-title":"MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts","volume":"110","author":"Vallet","year":"2007","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6840","DOI":"10.1158\/0008-5472.CAN-08-0402","article-title":"CC-chemokine ligand 20\/macrophage inflammatory protein-3\u03b1 and CC-chemokine receptor 6 are overexpressed in myeloma microenvironment related to osteolytic bone lesions","volume":"68","author":"Giuliani","year":"2008","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.cell.2007.12.037","article-title":"Tyrosine Kinases Btk and Tec Regulate Osteoclast Differentiation by Linking RANK and ITAM Signals","volume":"132","author":"Shinohara","year":"2008","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-018-0779-z","article-title":"Role of Bruton\u2019s tyrosine kinase in B cells and malignancies","volume":"17","author":"Dammeijer","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1158\/1078-0432.CCR-09-2329","article-title":"CXCL12 (SDF-1)\/CXCR4 Pathway in Cancer","volume":"16","author":"Teicher","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.jbo.2019.100253","article-title":"The role of CXCR4 in multiple myeloma: Cells\u2019 journey from bone marrow to beyond","volume":"17","author":"Ullah","year":"2019","journal-title":"J. Bone Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/ajh.23433","article-title":"Role of Bruton\u2019s tyrosine kinase in myeloma cell migration and induction of bone disease","volume":"88","author":"Bam","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s12185-009-0356-8","article-title":"Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma","volume":"90","author":"Bao","year":"2009","journal-title":"Int. J. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1182\/blood-2011-11-393348","article-title":"Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment","volume":"119","author":"Kurihara","year":"2012","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1182\/blood-2012-03-415588","article-title":"Clinical and prognostic role of annexin A2 in multiple myeloma","volume":"120","author":"Seckinger","year":"2012","journal-title":"Blood"},{"key":"ref_43","first-page":"174","article-title":"Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma","volume":"89","author":"Standal","year":"2004","journal-title":"Haematologica"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12079-009-0068-0","article-title":"The role of osteopontin in inflammatory processes","volume":"3","author":"Lund","year":"2009","journal-title":"J. Cell Commun. Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1158\/1078-0432.CCR-06-2258","article-title":"Myeloma Cell-Osteoclast Interaction Enhances Angiogenesis Together with Bone Resorption: A Role for Vascular Endothelial Cell Growth Factor and Osteopontin","volume":"13","author":"Tanaka","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_46","first-page":"513170","article-title":"Plasma Levels of Osteopontin and Vascular Endothelial Growth Factor in Association with Clinical Features and Parameters of Tumor Burden in Patients with Multiple Myeloma","volume":"2014","author":"Aralica","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/hon.803","article-title":"Osteopontin dysregulation and lytic bone lesions in multiple myeloma","volume":"25","author":"Robbiani","year":"2007","journal-title":"Hematol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1182\/blood.V118.21.3933.3933","article-title":"Bone Marrow Monocyte \/ Macrophage Derived Activin A Mediates the Osteoclastogenic Effects of IL-3 in Myeloma","volume":"118","author":"Silbermann","year":"2011","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1182\/blood-2003-06-1992","article-title":"IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells","volume":"103","author":"Lee","year":"2004","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3389\/fendo.2018.00788","article-title":"Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma","volume":"9","author":"Harmer","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.4049\/jimmunol.169.6.3353","article-title":"IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae","volume":"169","author":"Palmqvist","year":"2002","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1634\/stemcells.2005-0220","article-title":"A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: A potential role in the development of lytic bone disease and tumor progression in multiple myeloma","volume":"24","author":"Gunn","year":"2006","journal-title":"Stem Cells"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/cmi.2010.21","article-title":"Interleukin-17 and its expanding biological functions","volume":"7","author":"Xu","year":"2010","journal-title":"Cell. Mol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1182\/blood-2010-05-283895","article-title":"A novel role of IL-17\u2013producing lymphocytes in mediating lytic bone disease in multiple myeloma","volume":"116","author":"Noonan","year":"2010","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1530\/eje.0.1450225","article-title":"Expression and secretion of activin A: Possible physiological and clinical implications","volume":"145","author":"Luisi","year":"2001","journal-title":"Eur. J. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/jcb.10613","article-title":"Activin A stimulates IkappaB-alpha\/NFkappaB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors","volume":"90","author":"Sugatani","year":"2003","journal-title":"J. Cell Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5124","DOI":"10.1073\/pnas.0911929107","article-title":"Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease","volume":"107","author":"Vallet","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1006\/bbrc.2000.2075","article-title":"Activin A is an essential cofactor for osteoclast induction","volume":"268","author":"Fuller","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1093\/annonc\/mds068","article-title":"Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy","volume":"23","author":"Terpos","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"289458","DOI":"10.1155\/2013\/289458","article-title":"Cellular Mechanisms of Multiple Myeloma Bone Disease","volume":"2013","author":"Oranger","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/bjh.12835","article-title":"Sotatercept in patients with osteolytic lesions of multiple myeloma","volume":"165","author":"Abdulkadyrov","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1172\/JCI11176","article-title":"TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand","volume":"106","author":"Lam","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1084\/jem.189.11.1747","article-title":"BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth","volume":"189","author":"Schneider","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e282","DOI":"10.1038\/bcj.2015.3","article-title":"B-cell activating factor in the pathophysiology of multiple myeloma: A target for therapy?","volume":"5","author":"Hengeveld","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.bone.2010.12.023","article-title":"RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGF II","volume":"48","author":"Hemingway","year":"2011","journal-title":"Bone"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.leukres.2012.03.012","article-title":"Serum BAFF levels are related to angiogenesis and prognosis in patients with multiple myeloma","volume":"36","author":"Fragioudaki","year":"2012","journal-title":"Leuk. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1365-2141.2012.09241.x","article-title":"Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival","volume":"158","author":"Sanchez","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/bjh.14483","article-title":"Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma","volume":"176","author":"Raje","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.gene.2004.06.044","article-title":"Wnt signaling in osteoblasts and bone diseases","volume":"341","author":"Westendorf","year":"2004","journal-title":"Gene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1182\/blood-2008-11-191577","article-title":"Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma","volume":"114","author":"Fulciniti","year":"2009","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/1759720X12466608","article-title":"Wnt signaling in bone formation and its therapeutic potential for bone diseases","volume":"5","author":"Kim","year":"2013","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: From human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1749-6632.2011.06196.x","article-title":"Sclerostin is overexpressed by plasma cells from multiple myeloma patients","volume":"1237","author":"Brunetti","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13045-018-0615-3","article-title":"Wnt signaling in multiple myeloma: A central player in disease with therapeutic potential","volume":"11","author":"Spaan","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1182\/blood-2008-01-132134","article-title":"Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: A potential mechanism underlying osteolytic bone lesions in multiple myeloma","volume":"112","author":"Qiang","year":"2008","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.blre.2013.08.002","article-title":"Dickkopf-1 is a key regulator of myeloma bone disease: Opportunities and challenges for therapeutic intervention","volume":"27","author":"Zhou","year":"2013","journal-title":"Blood Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1158\/0008-5472.CAN-11-2067","article-title":"Bone Marrow Stromal Cells Create a Permissive Microenvironment for Myeloma Development: A New Stromal Role for Wnt Inhibitor Dkk1","volume":"72","author":"Fowler","year":"2012","journal-title":"Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1600-0609.2008.01065.x","article-title":"Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma","volume":"80","author":"Kaiser","year":"2008","journal-title":"Eur. J. Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1359\/jbmr.081104","article-title":"Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma","volume":"24","author":"Heath","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1182\/blood.V120.21.331.331","article-title":"Early Evidence of Anabolic Bone Activity of BHQ880, a Fully Human Anti-DKK1 Neutralizing Antibody: Results of a Phase 2 Study in Previously Untreated Patients with Smoldering Multiple Myeloma At Risk for Progression","volume":"120","author":"Munshi","year":"2012","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1182\/blood-2011-07-368472","article-title":"Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma","volume":"119","author":"Qian","year":"2012","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cytogfr.2005.02.005","article-title":"SOST\/sclerostin, an osteocyte-derived negative regulator of bone formation","volume":"16","author":"Papapoulos","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1177\/1759720X13510479","article-title":"Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases","volume":"6","author":"Lewiecki","year":"2014","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1093\/emboj\/cdg599","article-title":"Osteocyte control of bone formation via sclerostin, a novel BMP antagonist","volume":"22","author":"Winkler","year":"2003","journal-title":"EMBO J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1038\/bcj.2011.22","article-title":"Myeloma cells suppress osteoblasts through sclerostin secretion","volume":"1","author":"Colucci","year":"2011","journal-title":"Blood Cancer J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.leukres.2014.02.010","article-title":"Bone marrow plasma macrophage inflammatory protein protein-1 alpha(MIP-1 alpha) and sclerostin in multiple myeloma: Relationship with bone disease and clinical characteristics","volume":"38","author":"Wang","year":"2014","journal-title":"Leuk. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1002\/jbmr.2789","article-title":"Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease","volume":"31","author":"Eda","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1002\/ijc.27342","article-title":"Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: Reduction post-bortezomib monotherapy","volume":"131","author":"Terpos","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/jbmr.2351","article-title":"A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density","volume":"30","author":"Recker","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1182\/blood-2017-03-773341","article-title":"Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma","volume":"129","author":"McDonald","year":"2017","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1038\/leu.2017.152","article-title":"Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth","volume":"31","author":"Anderson","year":"2017","journal-title":"Leukemia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.3389\/fimmu.2018.02467","article-title":"Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy","volume":"9","author":"Toscani","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"269","DOI":"10.22203\/eCM.v028a19","article-title":"Role and regulation of RUNX2 in osteogenesis","volume":"28","author":"Bruderer","year":"2014","journal-title":"Eur. Cell Mater."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1182\/blood-2004-12-4986","article-title":"Myeloma cells block RUNX2\/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation","volume":"106","author":"Giuliani","year":"2005","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1182\/blood-2014-12-613968","article-title":"Myeloma cell-derived Runx2 promotes myeloma progression in bone","volume":"125","author":"Trotter","year":"2015","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cell.2008.03.011","article-title":"Eph-Ephrin Bidirectional Signaling in Physiology and Disease","volume":"133","author":"Pasquale","year":"2008","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1182\/blood-2009-01-201954","article-title":"The ephrinB2\/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth","volume":"114","author":"Pennisi","year":"2009","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cmet.2006.05.012","article-title":"Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis","volume":"4","author":"Zhao","year":"2006","journal-title":"Cell Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/annonc\/mdn796","article-title":"The use of bisphosphonates in multiple myeloma: Recommendations of an expert panel on behalf of the European Myeloma Network","volume":"20","author":"Terpos","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1200\/JCO.2017.76.6402","article-title":"Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update","volume":"36","author":"Anderson","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1006\/bbrc.1999.1499","article-title":"Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates","volume":"264","author":"Pieterman","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4103\/ijpvm.IJPVM_33_19","article-title":"Therapeutic Dimensions of Bisphosphonates: A Clinical Update","volume":"11","author":"Vannala","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/S0140-6736(10)62051-X","article-title":"First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): A randomised controlled trial","volume":"376","author":"Morgan","year":"2010","journal-title":"Lancet"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S1470-2045(11)70157-7","article-title":"Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): Secondary outcomes from a randomised controlled trial","volume":"12","author":"Morgan","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Du, J.-S., Yen, C.-H., Hsu, C.-M., and Hsiao, H.-H. (2021). Management of Myeloma Bone Lesions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073389"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ijc.24758","article-title":"The bisphosphonate zoledronic acid has antimyeloma activity in vivo by inhibition of protein prenylation","volume":"126","author":"Guenther","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_108","first-page":"2893","article-title":"Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients","volume":"9","author":"Santini","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/cncr.11701","article-title":"Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma","volume":"98","author":"Rosen","year":"2003","journal-title":"Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8","DOI":"10.6004\/jnccn.2022.0002","article-title":"NCCN Guidelines\u00ae Insights: Multiple Myeloma, Version 3.2022","volume":"20","author":"Callander","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1200\/JCO.18.02096","article-title":"Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline","volume":"37","author":"Mikhael","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.mayocp.2015.11.007","article-title":"Multiple Myeloma: Diagnosis and Treatment","volume":"91","author":"Rajkumar","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1634\/theoncologist.2010-0225","article-title":"The role of bisphosphonates in multiple myeloma: Mechanisms, side effects, and the future","volume":"16","author":"Pozzi","year":"2011","journal-title":"Oncologist"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1038\/ki.2008.356","article-title":"Bisphosphonate nephrotoxicity","volume":"74","author":"Perazella","year":"2008","journal-title":"Kidney Int."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1592\/phco.28.5.667","article-title":"Osteonecrosis of the jaw in patients receiving intravenous or oral bisphosphonates","volume":"28","author":"King","year":"2008","journal-title":"Pharmacotherapy"},{"key":"ref_117","first-page":"241","article-title":"Bisphosphonates and osteonecrosis of the jaws","volume":"17","author":"Urade","year":"2007","journal-title":"Clin. Calcium"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/j.1365-2141.2006.06230.x","article-title":"Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: A single-centre experience in 303 patients","volume":"134","author":"Zervas","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jocd.2008.02.002","article-title":"Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases","volume":"11","author":"Delmas","year":"2008","journal-title":"J. Clin. Densitom."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/ijcp.12022","article-title":"Denosumab: Mechanism of action and clinical outcomes","volume":"66","author":"Hanley","year":"2012","journal-title":"Int. J. Clin. Pract."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1185\/03007995.2015.1105795","article-title":"A comprehensive review of denosumab for bone metastasis in patients with solid tumors","volume":"32","author":"Sendur","year":"2016","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1200\/JCO.2010.31.3304","article-title":"Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma","volume":"29","author":"Henry","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ajh.21509","article-title":"An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma","volume":"84","author":"Vij","year":"2009","journal-title":"Am. J. Hematol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S1470-2045(18)30072-X","article-title":"Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: An international, double-blind, double-dummy, randomised, controlled, phase 3 study","volume":"19","author":"Raje","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1182\/bloodadvances.2020002378","article-title":"Denosumab compared with zoledronic acid on PFS in multiple myeloma: Exploratory results of an international phase 3 study","volume":"5","author":"Terpos","year":"2021","journal-title":"Blood Adv."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e207","DOI":"10.1016\/j.clml.2014.07.005","article-title":"Denosumab for the Management of Hypercalcemia of Malignancy in Patients With Multiple Myeloma and Renal Dysfunction","volume":"14","author":"Cicci","year":"2014","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_128","unstructured":"Newswire, P. (2022, February 13). FDA Approves XGEVA\u00ae (denosumab) for the Prevention of Skeletal-Related Events in Patients with Multiple Myeloma. Available online: https:\/\/www.centralcharts.com\/en\/338-amgen\/news\/1240693-fda-approves-xgeva-denosumab-for-the-prevention-of-skeletal-related-events-in-patients-with-multiple-myeloma."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"753","DOI":"10.3324\/haematol.2017.185264","article-title":"Denosumab for bone lesions in multiple myeloma\u2014What is its value?","volume":"103","author":"Goldstein","year":"2018","journal-title":"Haematologica"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bone.2017.08.003","article-title":"Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS","volume":"105","author":"Tsourdi","year":"2017","journal-title":"Bone"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Anastasilakis, A.D., Makras, P., Yavropoulou, M.P., Tabacco, G., Naciu, A.M., and Palermo, A. (2021). Denosumab Discontinuation and the Rebound Phenomenon: A Narrative Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010152"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1007\/s12325-020-01395-x","article-title":"Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study\u2014Asian Subgroup Analysis","volume":"37","author":"Huang","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Ito, S. (2020). Proteasome Inhibitors for the Treatment of Multiple Myeloma. Cancers, 12.","DOI":"10.3390\/cancers12020265"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1182\/blood-2007-03-067710","article-title":"Myeloma bone disease and proteasome inhibition therapies","volume":"110","author":"Terpos","year":"2007","journal-title":"Blood"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.bcmd.2004.01.001","article-title":"Pathogenesis of myeloma bone disease","volume":"32","author":"Roodman","year":"2004","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/ajh.21310","article-title":"The proteasome inhibitor, bortezomib suppresses primary myeloma and stimulates bone formation in myelomatous and nonmyelomatous bones in vivo","volume":"84","author":"Pennisi","year":"2009","journal-title":"Am. J. Hematol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1053\/j.seminhematol.2012.04.011","article-title":"Proteasome inhibitors and bone disease","volume":"49","author":"Qiang","year":"2012","journal-title":"Semin. Hematol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.4081\/hr.2018.7401","article-title":"Bone-targeted agents in multiple myeloma","volume":"10","author":"Nishida","year":"2018","journal-title":"Hematol. Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"172458","DOI":"10.1155\/2015\/172458","article-title":"Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling","volume":"2015","author":"Accardi","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Rasch, S., Lund, T., Asmussen, J.T., Lerberg Nielsen, A., Faebo Larsen, R., \u00d8sterheden Andersen, M., and Abildgaard, N. (2020). Multiple Myeloma Associated Bone Disease. Cancers, 12.","DOI":"10.20944\/preprints202007.0041.v1"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s11914-017-0397-5","article-title":"Myeloma and Bone Disease","volume":"15","author":"Panaroni","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41408-019-0187-7","article-title":"The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: A consensus statement from the International Myeloma Working Group (IMWG)","volume":"9","author":"Kyriakou","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1182\/blood.V114.22.750.750","article-title":"A Phase I\/II Study of BHQ880, a Novel Osteoblat Activating, Anti-DKK1 Human Monoclonal Antibody, in Relapsed and Refractory Multiple Myeloma (MM) Patients Treated with Zoledronic Acid (Zol) and Anti-Myeloma Therapy (MM Tx)","volume":"114","author":"Padmanabhan","year":"2009","journal-title":"Blood"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/bjh.13056","article-title":"A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events","volume":"167","author":"Iyer","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1038\/leu.2013.50","article-title":"Lenalidomide in combination with an activin A-neutralizing antibody: Preclinical rationale for a novel anti-myeloma strategy","volume":"27","author":"Scullen","year":"2013","journal-title":"Leukemia"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1182\/blood.V126.23.4241.4241","article-title":"Phase 1 dose-escalation study of sotatercept (ACE-011) in combination with lenalidomide and dexamethasone in patients with relapsed and\/or refractory multiple myeloma","volume":"126","author":"Yee","year":"2015","journal-title":"Blood"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1158\/1078-0432.CCR-16-0201","article-title":"Phase 1 Study of Tabalumab, a Human Anti-B-Cell Activating Factor Antibody, and Bortezomib in Patients with Relapsed\/Refractory Multiple Myeloma","volume":"22","author":"Raje","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1111\/cas.13000","article-title":"Dose-escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma","volume":"107","author":"Iida","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/bjh.15058","article-title":"Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: Phase 2 trial results","volume":"180","author":"Richardson","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1080\/15384047.2016.1156261","article-title":"Anti-myeloma effect of pharmacological inhibition of Notch\/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment","volume":"17","author":"Pisklakova","year":"2016","journal-title":"Cancer Biol Ther."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1038\/bcj.2014.37","article-title":"Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model","volume":"4","author":"Schwarzer","year":"2014","journal-title":"Blood Cancer J."},{"key":"ref_152","first-page":"318","article-title":"Abstract #318: The CCR1 inhibitor, MLN3897, enhances Velcade inhibition of multiple myeloma (MM)-bone cells interactions","volume":"69","author":"Vallet","year":"2009","journal-title":"Cancer Res."},{"key":"ref_153","first-page":"121","article-title":"Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor","volume":"7","author":"Manetta","year":"2014","journal-title":"J. Inflamm. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1158\/1078-0432.CCR-07-0753","article-title":"Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model","volume":"13","author":"Neri","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1182\/blood-2011-12-396853","article-title":"Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma","volume":"120","author":"Tai","year":"2012","journal-title":"Blood"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.maturitas.2014.04.016","article-title":"Anti-sclerostin antibodies: Utility in treatment of osteoporosis","volume":"78","author":"Clarke","year":"2014","journal-title":"Maturitas"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:36:10Z","timestamp":1760135770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":156,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23063112"],"URL":"https:\/\/doi.org\/10.3390\/ijms23063112","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]}}}