Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies
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Moreau, P., San Miguel, J., Sonneveld, P., Mateos, M.V., Zamagni, E., Avet-Loiseau, H., Hajek, R., Dimopoulos, M.A., Ludwig, H., and Einsele, H. (2017). Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol.
Rodriguez, 1972, Bone healing in multiple myeloma with melphalan chemotherapy, Ann. Intern. Med., 76, 551, 10.7326/0003-4819-76-4-551
Schulze, M., Weisel, K., Grandjean, C., Oehrlein, K., Zago, M., Spira, D., and Horger, M. (2014). Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: Results of a reduced-dose whole-body MDCT study. Am. J. Roentgenol.
Hinge, 2016, Bone healing in multiple myeloma: A prospective evaluation of the impact of first-line anti-myeloma treatment, Haematologica, 101, e419, 10.3324/haematol.2016.144477
Silbermann, 2013, Myeloma bone disease: Pathophysiology and management, J. Bone Oncol., 2, 59, 10.1016/j.jbo.2013.04.001
Zagouri, 2017, Hypercalcemia remains an adverse prognostic factor for newly diagnosed multiple myeloma patients in the era of novel antimyeloma therapies, Eur. J. Haematol., 99, 409, 10.1111/ejh.12923
Sonmez, M., Akagun, T., Topbas, M., Cobanoglu, U., Sonmez, B., Yilmaz, M., Ovali, E., and Omay, S.B. (2008). Effect of pathologic fractures on survival in multiple myeloma patients: A case control study. J. Exp. Clin. Cancer Res., 27.
Terpos, 2018, Pathogenesis of bone disease in multiple myeloma: From bench to bedside, Blood Cancer J., 8, 7, 10.1038/s41408-017-0037-4
Pianko, 2014, Whole-body low-dose computed tomography and advanced imaging techniques for multiple myeloma bone disease, Clin. Cancer Res., 20, 5888, 10.1158/1078-0432.CCR-14-1692
Hillengass, 2017, Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: A study of the International Myeloma Working Group, Blood Cancer J., 7, e599, 10.1038/bcj.2017.78
Cavo, 2017, Role of 18 F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: A consensus statement by the International Myeloma Working Group, Lancet Oncol., 18, e206, 10.1016/S1470-2045(17)30189-4
Raje, 2018, Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: An international, double-blind, double-dummy, randomised, controlled, phase 3 study, Lancet Oncol., 19, 370, 10.1016/S1470-2045(18)30072-X
Vallet, 2010, Novel bone-targeted strategies in oncology, Clin. Cancer Res., 16, 4084, 10.1158/1078-0432.CCR-10-0600
Buckwalter, 1995, Bone biology. Part I: Structure, blood supply, cells, matrix, and mineralization, J. Bone Jt. Surg. Ser. A, 45, 371
Raggatt, 2010, Cellular and molecular mechanisms of bone remodeling, J. Biol. Chem., 285, 25103, 10.1074/jbc.R109.041087
Teitelbaum, 2003, Genetic regulation of osteoclast development and function, Nat. Rev. Genet., 4, 638, 10.1038/nrg1122
Boyce, 2008, Functions of RANKL/RANK/OPG in bone modeling and remodeling, Arch. Biochem. Biophys., 473, 139, 10.1016/j.abb.2008.03.018
Huang, 2007, Signaling and transcriptional regulation in osteoblast commitment and differentiation, Front. Biosci., 1, 3068, 10.2741/2296
Harada, 2003, Control of osteoblast function and regulation of bone mass, Nature, 423, 349, 10.1038/nature01660
Nakashima, 2011, Evidence for osteocyte regulation of bone homeostasis through RANKL expression, Nat. Med., 17, 1231, 10.1038/nm.2452
Winkler, 2003, Osteocyte control of bone formation via sclerostin, a novel BMP antagonist, EMBO J., 22, 6267, 10.1093/emboj/cdg599
Christenson, 1997, Biochemical markers of bone metabolism: An overview, Clin. Biochem., 30, 573, 10.1016/S0009-9120(97)00113-6
Arnulf, 2007, Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma, Leukemia, 21, 158, 10.1038/sj.leu.2404466
Roccaro, 2013, BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression, J. Clin. Investig., 123, 1542, 10.1172/JCI66517
Wang, 2014, Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells, Blood, 123, 1542
Umezu, 2014, Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1, Blood, 124, 3748, 10.1182/blood-2014-05-576116
Podar, 2011, The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: Therapeutic implications, Br. J. Haematol., 155, 438, 10.1111/j.1365-2141.2011.08864.x
Fan, 2017, The AP-1 transcription factor JunB is essential for multiple myeloma cell proliferation and drug resistance in the bone marrow microenvironment, Leukemia, 31, 1570, 10.1038/leu.2016.358
Abe, 2004, Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: A vicious cycle between bone destruction and myeloma expansion, Blood, 104, 2484, 10.1182/blood-2003-11-3839
Li, 2008, Role of decorin in the antimyeloma effects of osteoblasts, Blood, 112, 159, 10.1182/blood-2007-11-124164
Yaccoby, 2006, Inhibitory effects of osteoblasts and increased bone formation on myeloma in novel culture systems and a myelomatous mouse model, Haematologica, 91, 192
Lawson, 2015, Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche, Nat. Commun., 6, 8993, 10.1038/ncomms9983
Anderson, 2016, Bidirectional notch signaling and osteocyte-derived factors in the bone marrow microenvironment promote tumor cell proliferation and bone destruction in multiple myeloma, Cancer Res., 76, 1089, 10.1158/0008-5472.CAN-15-1703
Trotter, 2016, Adipocyte-Lineage Cells Support Growth and Dissemination of Multiple Myeloma in Bone, Am. J. Pathol., 186, 3054, 10.1016/j.ajpath.2016.07.012
Caers, 2007, Neighboring adipocytes participate in the bone marrow microenvironment of multiple myeloma cells, Leukemia, 21, 1580, 10.1038/sj.leu.2404658
Bullwinkle, 2016, Adipocytes contribute to the growth and progression of multiple myeloma: Unraveling obesity related differences in adipocyte signaling, Cancer Lett., 380, 114, 10.1016/j.canlet.2016.06.010
Pang, 2017, Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression, Haematologica, 102, 1273, 10.3324/haematol.2016.154062
Pratt, 2007, Immunodeficiency and immunotherapy in multiple myeloma, Br. J. Haematol., 138, 563, 10.1111/j.1365-2141.2007.06705.x
Favreau, 2017, Leptin receptor antagonism of iNKT cell function: A novel strategy to combat multiple myeloma, Leukemia, 31, 2678, 10.1038/leu.2017.146
Prabhala, 2010, Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma, Blood, 115, 5385, 10.1182/blood-2009-10-246660
Meade, 2007, The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells, Cancer Res., 67, 8444, 10.1158/0008-5472.CAN-06-4230
Benson, 2010, The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: A therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody, Blood, 116, 2286, 10.1182/blood-2010-02-271874
Costello, 2013, Differential expression of natural killer cell activating receptors in blood versus bone marrow in patients with monoclonal gammopathy, Immunology, 139, 338, 10.1111/imm.12082
Chauhan, 2009, Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: A therapeutic target, Cancer Cell, 16, 309, 10.1016/j.ccr.2009.08.019
Tai, 2018, Osteoclast Immunosuppressive Effects in Multiple Myeloma: Role of Programmed Cell Death Ligand 1, Front. Immunol., 10, 1822, 10.3389/fimmu.2018.01822
Melton, 2004, Fracture risk in monoclonal gammopathy of undetermined significance, J. Bone Miner. Res., 19, 25, 10.1359/jbmr.0301212
Bataille, 1989, Mechanisms of bone destruction in multiple myeloma: The importance of an unbalanced process in determining the severity of lytic bone disease, J. Clin. Oncol., 7, 1909, 10.1200/JCO.1989.7.12.1909
Bataille, 1996, Quantifiable excess of bone resorption in monoclonal gammopathy is an early symptom of malignancy: A prospective study of 87 bone biopsies, Blood, 87, 4762, 10.1182/blood.V87.11.4762.bloodjournal87114762
Vallet, 2018, A role for bone turnover markers β-CrossLaps (CTX) and amino-terminal propeptide of type I collagen (PINP) as potential indicators for disease progression from MGUS to multiple myeloma, Leuk. Lymphoma, 18, 1
Terpos, 2010, The use of biochemical markers of bone remodeling in multiple myeloma: A report of the International Myeloma Working Group, Leukemia, 24, 1700, 10.1038/leu.2010.173
Raimondi, 2015, Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation, Oncotarget, 6, 13772, 10.18632/oncotarget.3830
Giuliani, 2012, Increased osteocyte death in multiple myeloma patients: Role in myeloma-induced osteoclast formation, Leukemia, 26, 1391, 10.1038/leu.2011.381
Kong, 1999, OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis, Nature, 397, 315, 10.1038/16852
Giuliani, 2002, Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: A potential role in multiple myeloma bone disease, Blood, 100, 4615, 10.1182/blood-2002-04-1121
Sezer, 2003, RANK ligand and osteoprotegerin in myeloma bone disease, Blood, 101, 2094, 10.1182/blood-2002-09-2684
Kopan, 2009, The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism, Cell, 137, 216, 10.1016/j.cell.2009.03.045
Previs, 2015, Molecular pathways: Translational and therapeutic implications of the Notch signaling pathway in cancer, Clin. Cancer Res., 21, 955, 10.1158/1078-0432.CCR-14-0809
Colombo, 2013, Notch-directed microenvironment reprogramming in myeloma: A single path to multiple outcomes, Leukemia, 27, 1009, 10.1038/leu.2013.6
Colombo, 2014, Notch signaling drives multiple myeloma induced osteoclastogenesis, Oncotarget, 5, 10393, 10.18632/oncotarget.2084
Vallet, 2007, MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts, Blood, 110, 3744, 10.1182/blood-2007-05-093294
Matsumoto, 2006, Bone destruction in multiple myeloma, Ann. N. Y. Acad. Sci., 1068, 319, 10.1196/annals.1346.035
Tsubaki, 2007, Macrophage inflammatory protein-1alpha (MIP-1alpha) enhances a receptor activator of nuclear factor kappaB ligand (RANKL) expression in mouse bone marrow stromal cells and osteoblasts through MAPK and PI3K/Akt pathways, Mol. Cell. Biochem., 304, 53, 10.1007/s11010-007-9485-7
Terpos, 2003, Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) correlate with the extent of bone disease and survival in patients with multiple myeloma, Br. J. Haematol., 123, 106, 10.1046/j.1365-2141.2003.04561.x
Giuliani, 2008, CC-Chemokine ligand 20/macrophage inflammatory protein-3alpha and CC-chemokine receptor 6 are overexpressed in myeloma microenvironment related to osteolytic bone lesions, Cancer Res., 68, 6840, 10.1158/0008-5472.CAN-08-0402
Guasco, 2016, Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20, Leukemia, 30, 409, 10.1038/leu.2015.259
Hideshima, 2001, The role of tumor necrosis factor α in the pathophysiology of human multiple myeloma: Therapeutic applications, Oncogene, 20, 4519, 10.1038/sj.onc.1204623
Lam, 2000, TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand, J. Clin. Investig., 106, 1481, 10.1172/JCI11176
Lu, 2006, Transcriptional regulation of the osterix (Osx, Sp7) promoter by tumor necrosis factor identifies disparate effects of mitogen-activated protein kinase and NF kappa B pathways, J. Biol. Chem., 281, 6297, 10.1074/jbc.M507804200
Udagawa, 1995, Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors, J. Exp. Med., 182, 1461, 10.1084/jem.182.5.1461
Lee, 2004, IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells, Blood, 103, 2308, 10.1182/blood-2003-06-1992
Ehrlich, 2005, IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma, Blood, 106, 1407, 10.1182/blood-2005-03-1080
Silbermann, 2014, Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma, Leukemia, 28, 951, 10.1038/leu.2013.385
Noonan, 2010, A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma, Blood, 116, 3554, 10.1182/blood-2010-05-283895
Kawano, 1989, Interleukin-1 beta rather than lymphotoxin as the major bone resorbing activity in human multiple myeloma, Blood, 73, 1646, 10.1182/blood.V73.6.1646.1646
Hjertner, 1999, Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: A possible role for HGF in myeloma-associated osteolytic bone disease, Blood, 94, 3883, 10.1182/blood.V94.11.3883
Bennett, 2005, Regulation of osteoblastogenesis and bone mass by Wnt10b, Proc. Natl. Acad. Sci. USA, 102, 3324, 10.1073/pnas.0408742102
Boyden, 2002, High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5, N. Engl. J. Med., 346, 1513, 10.1056/NEJMoa013444
Baron, 2013, WNT signaling in bone homeostasis and disease: From human mutations to treatments, Nat. Med., 19, 179, 10.1038/nm.3074
Spaan, 2018, Wnt signaling in multiple myeloma: A central player in disease with therapeutic potential, J. Hematol. Oncol., 11, 67, 10.1186/s13045-018-0615-3
Politou, 2006, Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation, Int. J. Cancer, 119, 1728, 10.1002/ijc.22033
Eda, 2016, Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease, J. Bone Miner. Res., 31, 1225, 10.1002/jbmr.2789
Leupin, 2011, Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function, J. Biol. Chem., 286, 19489, 10.1074/jbc.M110.190330
Sato, 2017, Role and mechanism of action of sclerostin in bone, Bone, 96, 29, 10.1016/j.bone.2016.10.007
Kamiya, 2008, BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway, Development, 135, 3801, 10.1242/dev.025825
Anderson, 2017, Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth, Leukemia, 31, 2686, 10.1038/leu.2017.152
Tian, 2003, The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma, N. Engl. J. Med., 349, 2483, 10.1056/NEJMoa030847
Gunn, 2006, 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, Stem Cells, 24, 986, 10.1634/stemcells.2005-0220
Wu, 2011, A gene expression-based predictor for myeloma patients at high risk of developing bone disease on bisphosphonate treatment, Clin. Cancer Res., 17, 6347, 10.1158/1078-0432.CCR-11-0994
Bolzoni, 2013, Myeloma cells inhibit non-canonical wnt co-receptor ror2 expression in human bone marrow osteoprogenitor cells: Effect of wnt5a/ror2 pathway activation on the osteogenic differentiation impairment induced by myeloma cells, Leukemia, 27, 451, 10.1038/leu.2012.190
Vallet, 2010, Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease, Proc. Natl. Acad. Sci. USA, 107, 5124, 10.1073/pnas.0911929107
Fuller, 2000, Activin A is an essential cofactor for osteoclast induction, Biochem. Biophys. Res. Commun., 268, 2, 10.1006/bbrc.2000.2075
Giuliani, 2005, Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation, Blood, 106, 2472, 10.1182/blood-2004-12-4986
Vallet, 2011, A novel role for CCL3 (MIP-1α) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function, Leukemia, 25, 1174, 10.1038/leu.2011.43
Kassen, 2016, Myeloma impairs mature osteoblast function but causes early expansion of osteo-progenitors: Temporal changes in bone physiology and gene expression in the KMS12BM model, Br. J. Haematol., 172, 64, 10.1111/bjh.13790
Anderson, 2018, Role of bone-modifying agents in multiple myeloma: American society of clinical oncology clinical practice guideline update, J. Clin. Oncol., 36, 812, 10.1200/JCO.2017.76.6402
Vallet, 2013, New insights, recent advances, and current challenges in the biological treatment of multiple myeloma, Expert Opin. Biol. Ther., 13, S35, 10.1517/14712598.2013.807337
Raje, 2000, Introduction: The evolving role of bisphosphonate therapy in multiple myeloma, Blood, 96, 381, 10.1182/blood.V96.2.381.014k54_381_383
Dunford, 2008, Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: Time-dependent inhibition of human farnesyl pyrophosphate synthase, J. Med. Chem., 51, 2187, 10.1021/jm7015733
Morgan, 2010, First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): A randomised controlled trial, Lancet, 376, 1989, 10.1016/S0140-6736(10)62051-X
Kyle, 2007, American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma, J. Clin. Oncol., 25, 2464, 10.1200/JCO.2007.12.1269
Raje, 2008, Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw, Clin. Cancer Res., 14, 2387, 10.1158/1078-0432.CCR-07-1430
Schilcher, 2009, Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate, Acta Orthop., 80, 413, 10.3109/17453670903139914
Black, 2010, Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur, N. Engl. J. Med., 362, 1761, 10.1056/NEJMoa1001086
Allen, 2011, Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don’t know, Bone, 49, 56, 10.1016/j.bone.2010.10.159
Boskey, 2012, Atypical subtrochanteric femoral shaft fractures: Role for mechanics and bone quality, Arthritis Res. Ther., 14, 220, 10.1186/ar4013
Raje, 2016, Bone marker-directed dosing of zoledronic acid for the prevention of skeletal complications in patients with multiple myeloma: Results of the Z-MARK study, Clin. Cancer Res., 22, 1378, 10.1158/1078-0432.CCR-15-1864
Kostenuik, 2009, Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL, J. Bone Miner. Res., 24, 182, 10.1359/jbmr.081112
McClung, 2006, Denosumab in postmenopausal women with low bone mineral density, N. Engl. J. Med., 354, 821, 10.1056/NEJMoa044459
Lipton, 2007, Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases, J. Clin. Oncol., 25, 4431, 10.1200/JCO.2007.11.8604
Vij, 2009, An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma, Am. J. Hematol., 84, 650, 10.1002/ajh.21509
Henry, 2011, 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, J. Clin. Oncol., 29, 1125, 10.1200/JCO.2010.31.3304
Raje, 2016, Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial, Blood Cancer J., 6, e378, 10.1038/bcj.2015.96
Terpos, 2017, Comparison of denosumab with zoledronic acid for the treatment of bone disease in patients with newly diagnosed Multiple Myeloma; an international, randomized, double blind trial, EHA, 102, S782
Roccaro, 2006, Bortezomib as an antitumor agent, Curr. Pharm. Biotechnol., 7, 441, 10.2174/138920106779116865
Mukherjee, 2008, Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice, J. Clin. Investig., 118, 491
Krebbel, 2007, Bortezomib inhibits human osteoclastogenesis, Leukemia, 21, 2025, 10.1038/sj.leu.2404806
Zangari, 2005, Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma, Br. J. Haematol., 131, 71, 10.1111/j.1365-2141.2005.05733.x
Giuliani, 2007, The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients, Blood, 110, 334, 10.1182/blood-2006-11-059188
Lund, 2010, First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro, Eur. J. Haematol., 85, 290, 10.1111/j.1600-0609.2010.01485.x
Toscani, 2016, The Proteasome Inhibitor Bortezomib Maintains Osteocyte Viability in Multiple Myeloma Patients by Reducing both Apoptosis and Autophagy: A New Function for Proteasome Inhibitors, J. Bone Miner. Res., 31, 815, 10.1002/jbmr.2741
Anderson, 2006, Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1, Blood, 107, 3098, 10.1182/blood-2005-08-3450
Breitkreutz, 2008, Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma, Leukemia, 22, 1925, 10.1038/leu.2008.174
Bolzoni, 2012, Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules, Exp. Hematol., 41, 387, 10.1016/j.exphem.2012.11.005
Terpos, 2010, Circulating Levels of the Wnt Inhibitors Dickkopf-1 and Sclerostin in Different Phases of Multiple Myeloma: Alterations Post-Therapy with Lenalidomide and Dexamethasone with or without Bortezomib, Blood, 116, 2963, 10.1182/blood.V116.21.2963.2963
Fulciniti, 2009, Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma, Blood, 114, 371, 10.1182/blood-2008-11-191577
Qian, 2012, Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma, Blood, 119, 161, 10.1182/blood-2011-07-368472
Pozzi, 2013, In vivo and in vitro effects of a novel anti-Dkk1 neutralizing antibody in multiple myeloma, Bone, 53, 487, 10.1016/j.bone.2013.01.012
Heath, 2008, Inhibiting Dickkopf-1 (Dkk1) Removes Suppression of Bone Formation and Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma, J. Bone Miner. Res., 24, 425, 10.1359/jbmr.081104
Munshi, 2012, 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, Blood, 120, 331, 10.1182/blood.V120.21.331.331
Iyer, 2014, 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, Br. J. Haematol., 167, 366, 10.1111/bjh.13056
Cosman, 2016, Romosozumab Treatment in Postmenopausal Women with Osteoporosis, N. Engl. J. Med., 375, 1532, 10.1056/NEJMoa1607948
McDonald, 2017, Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma, Blood, 129, 3452, 10.1182/blood-2017-03-773341
McDonald, 2017, Sclerostin: An Emerging Target for the Treatment of Cancer-Induced Bone Disease, Curr. Osteoporos. Rep., 15, 532, 10.1007/s11914-017-0403-y
Raje, 2010, Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss, Curr. Opin. Mol. Ther., 12, 586
Abdulkadyrov, 2014, Sotatercept in patients with osteolytic lesions of multiple myeloma, Br. J. Haematol., 165, 814, 10.1111/bjh.12835
Scullen, 2013, Lenalidomide in combination with an activin A-neutralizing antibody: Preclinical rationale for a novel anti-myeloma strategy, Leukemia, 27, 1715, 10.1038/leu.2013.50
Adamik, 2017, EZH2 or HDAC1 Inhibition Reverses Multiple Myeloma–Induced Epigenetic Suppression of Osteoblast Differentiation, Mol. Cancer Res., 15, 405, 10.1158/1541-7786.MCR-16-0242-T
Deleu, 2009, The effects of JNJ-26481585, a novel hydroxamate-based histone deacetylase inhibitor, on the development of multiple myeloma in the 5T2MM and 5T33MM murine models, Leukemia, 23, 1894, 10.1038/leu.2009.121
Xu, 2013, Effect of the HDAC inhibitor vorinostat on the osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo, Acta Pharmacol. Sin., 34, 699, 10.1038/aps.2012.182
Mirandola, 2013, Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1, Leukemia, 27, 1558, 10.1038/leu.2013.27
Schwarzer, 2014, Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model, Blood Cancer J., 4, e217, 10.1038/bcj.2014.37
Wei, 2010, Evaluation of Selective Gamma-Secretase Inhibitor PF-03084014 for Its Antitumor Efficacy and Gastrointestinal Safety to Guide Optimal Clinical Trial Design, Mol. Cancer Ther., 9, 1618, 10.1158/1535-7163.MCT-10-0034
Krop, 2012, Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors, J. Clin. Oncol., 30, 2307, 10.1200/JCO.2011.39.1540
Wu, 2010, Therapeutic antibody targeting of individual Notch receptors, Nature, 464, 1052, 10.1038/nature08878
Chiorean, 2015, A phase I first-in-human study of enoticumab (REGN421), a fully human delta-like ligand 4 (Dll4) monoclonal antibody in patients with advanced solid tumors, Clin. Cancer Res., 21, 2695, 10.1158/1078-0432.CCR-14-2797
Vallet, 2011, CCR1 as a target for multiple myeloma, Expert Opin. Ther. Targets, 15, 1037, 10.1517/14728222.2011.586634
Menu, 2006, Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: A study in the 5TMM model, Clin. Exp Metastasis, 23, 291, 10.1007/s10585-006-9038-6
Prabhala, 2016, Targeting IL-17A in multiple myeloma: A potential novel therapeutic approach in myeloma, Leukemia, 30, 379, 10.1038/leu.2015.228
Fulciniti, 2009, A high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma, Clin. Cancer Res., 15, 7144, 10.1158/1078-0432.CCR-09-1483
Tai, 2012, Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma, Blood, 120, 1877, 10.1182/blood-2011-12-396853