{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:13:35Z","timestamp":1776273215478,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Carfilzomib with dexamethasone (Kd) is a well-established regimen for the treatment of relapsed\/refractory multiple myeloma (RRMM). There is limited information for the effects of Kd on myeloma-related bone disease. This non-interventional study aimed to assess skeletal-related events (SREs) and bone metabolism in patients with RRMM receiving Kd, in the absence of any bone-targeted agent. Twenty-five patients were enrolled with a median of three prior lines of therapy; 72% of them had evidence of osteolytic bone disease at study entry. During Kd treatment, the rate of new SREs was 28%. Kd produced a clinically relevant (\u226530%) decrease in C-telopeptide of collagen type-1 (p = 0.048) and of tartrate-resistant acid phosphatase-5b (p = 0.002) at 2 months. This reduction was at least partially due to the reduction in the osteoclast regulator RANKL\/osteoprotegerin ratio, at 2 months (p = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months (p = 0.03) and in procollagen type I N-propeptide at 8 months post-Kd initiation. Importantly, these bone metabolism changes were independent of myeloma response to treatment. In conclusion, Kd resulted in a low rate of SREs among RRMM patients, along with an early, sustained and clinically relevant decrease in bone resorption, which was accompanied by an increase in bone formation, independently of myeloma response and in the absence of any bone-targeted agent use.<\/jats:p>","DOI":"10.3390\/cancers13061257","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T11:56:55Z","timestamp":1615550215000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed\/Refractory Multiple Myeloma: Results of the CarMMa Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-1422","authenticated-orcid":false,"given":"Evangelos","family":"Terpos","sequence":"first","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Ntanasis-Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Katodritou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Theagenio Cancer Hospital, PS 54639 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Christine","family":"Kyrtsonis","sequence":"additional","affiliation":[{"name":"First Department of Propedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassiliki","family":"Douka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation Unit, General Hospital \u201cG.Papanikolaou\u201d, PS 57010 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-5862","authenticated-orcid":false,"given":"Emmanouil","family":"Spanoudakis","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, Democritus University of Thrace, PS 68131 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Papatheodorou","sequence":"additional","affiliation":[{"name":"Department of Medical Research, 251 General Air-Force Hospital, PS 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3407-5994","authenticated-orcid":false,"given":"Evangelos","family":"Eleutherakis-Papaiakovou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Kanellias","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Gavriatopoulou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-3357","authenticated-orcid":false,"given":"Polyzois","family":"Makras","sequence":"additional","affiliation":[{"name":"Department of Medical Research, 251 General Air-Force Hospital, PS 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-5832","authenticated-orcid":false,"given":"Efstathios","family":"Kastritis","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","unstructured":"Mateos, M.V., Fink, L., Koneswaran, N., Intorcia, M., Giannopoulou, C., Niepel, D., and Cavo, M. (2020). Bone complications in patients with multiple myeloma in five European countries: A retrospective patient chart review. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6596-y"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.annonc.2020.07.019","article-title":"Bone health in cancer: ESMO Clinical Practice Guidelines","volume":"31","author":"Coleman","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Terpos, E., Zamagni, E., Lentzsch, S., Drake, M.T., Garcia-Sanz, R., Abildgaard, N., Ntanasis-Stathopoulos, I., Schjesvold, F., de la Rubia, J., and Kyriakou, C. (2021). Treatment of multiple myeloma-related bone disease: Recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol.","DOI":"10.1016\/S1470-2045(20)30559-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41408-020-0297-2","article-title":"Consolidation with carfilzomib, lenalidomide, and dexamethasone (KRd) following ASCT results in high rates of minimal residual disease negativity and improves bone metabolism, in the absence of bisphosphonates, among newly diagnosed patients with multiple myeloma","volume":"10","author":"Gavriatopoulou","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ajh.25392","article-title":"Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates","volume":"94","author":"Terpos","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/leu.2013.267","article-title":"VTD consolidation, without bisphosphonates, reduces bone resorption and is associated with a very low incidence of skeletal-related events in myeloma patients post ASCT","volume":"28","author":"Terpos","year":"2014","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/cncr.28481","article-title":"The effects of bortezomib on bone disease in patients with multiple myeloma","volume":"120","author":"Mohty","year":"2014","journal-title":"Cancer"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.bone.2016.02.019","article-title":"The effects of proteasome inhibitors on bone remodeling in multiple myeloma","volume":"86","author":"Zangari","year":"2016","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1038\/leu.2008.235","article-title":"The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed\/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis","volume":"22","author":"Terpos","year":"2008","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1600-0609.2011.01599.x","article-title":"Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma","volume":"86","author":"Delforge","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/j.1365-2141.2006.06356.x","article-title":"Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma","volume":"135","author":"Terpos","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/sj.leu.2404843","article-title":"The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma","volume":"21","author":"Terpos","year":"2007","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.ctrv.2011.12.007","article-title":"Impact of bortezomib on bone health in myeloma: A review of current evidence","volume":"38","author":"Zangari","year":"2012","journal-title":"Cancer Treat. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S1470-2045(15)00464-7","article-title":"Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre study","volume":"17","author":"Dimopoulos","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_18","first-page":"e528","article-title":"Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up","volume":"5","author":"Dimopoulos","year":"2021","journal-title":"HemaSphere"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ntanasis-Stathopoulos, I., Gavriatopoulou, M., Terpos, E., and Dimopoulos, M.A. (2021). Real World Treatment of Patients with Relapsed\/Refractory Myeloma. Clin. Lymphoma Myeloma Leuk.","DOI":"10.1016\/j.clml.2021.01.018"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/j.1600-0609.2011.01602.x","article-title":"Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients","volume":"86","author":"Zangari","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1016\/S1470-2045(16)30206-6","article-title":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","volume":"17","author":"Kumar","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta18110","article-title":"Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: The secondary prevention of fractures, and primary prevention of fractures in high-risk groups","volume":"18","author":"Burch","year":"2014","journal-title":"Health Technol. Assess."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1359\/JBMR.0301243","article-title":"Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk","volume":"19","author":"Sarkar","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100215","DOI":"10.1016\/j.jbo.2018.100215","article-title":"Incidence of skeletal-related events among multiple myeloma patients in the United States at oncology clinics: Observations from real-world data","volume":"14","author":"Kim","year":"2019","journal-title":"J. Bone Oncol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"100272","DOI":"10.1016\/j.bonr.2020.100272","article-title":"What is the relationship between bone turnover markers and skeletal-related events in patients with bone metastases from solid tumors and in patients with multiple myeloma? A systematic review and meta-regression analysis","volume":"12","author":"Jiang","year":"2020","journal-title":"Bone Rep."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1038\/leu.2010.173","article-title":"The use of biochemical markers of bone remodeling in multiple myeloma: A report of the International Myeloma Working Group","volume":"24","author":"Terpos","year":"2010","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/ijc.32125","article-title":"Effect of induction therapy with lenalidomide, doxorubicin and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma","volume":"145","author":"Terpos","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1182\/blood-2012-10-459883","article-title":"Carfilzomib","volume":"121","author":"Kortuem","year":"2013","journal-title":"Blood"},{"key":"ref_31","first-page":"1826","article-title":"Phase 2 Study of Carfilzomib and Bone Metabolism in Patients with Relapsed Multiple Myeloma","volume":"130","author":"Suvannasankha","year":"2017","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41408-017-0037-4","article-title":"Pathogenesis of bone disease in multiple myeloma: From bench to bedside","volume":"8","author":"Terpos","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/leu.2012.183","article-title":"The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects","volume":"27","author":"Hurchla","year":"2013","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1038\/leu.2014.69","article-title":"A novel Bruton\u2019s tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant antimyeloma activity","volume":"28","author":"Eda","year":"2014","journal-title":"Leukemia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Takito, J., Inoue, S., and Nakamura, M. (2018). The Sealing Zone in Osteoclasts: A Self-Organized Structure on the Bone. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040984"},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"16918","DOI":"10.1074\/jbc.M115.663963","article-title":"The Proteasome Inhibitor Carfilzomib Suppresses Parathyroid Hormone-induced Osteoclastogenesis through a RANKL-mediated Signaling Pathway","volume":"290","author":"Yang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_38","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_39","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_40","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1046\/j.1365-2141.2003.04561.x","article-title":"Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) correlate with the extent of bone disease and survival in patients with multiple myeloma","volume":"123","author":"Terpos","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1038\/leu.2009.130","article-title":"Increased expression of macrophage inflammatory protein-1alpha on trephine biopsies correlates with extensive bone disease, increased angiogenesis and advanced stage in newly diagnosed patients with multiple myeloma","volume":"23","author":"Roussou","year":"2009","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/leu.2011.43","article-title":"A novel role for CCL3 (MIP-1alpha) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function","volume":"25","author":"Vallet","year":"2011","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-3-030-36667-4_2","article-title":"CCL3 Signaling in the Tumor Microenvironment","volume":"1231","author":"Fotiou","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41408-018-0075-6","article-title":"Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma","volume":"8","author":"Terpos","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hu, B., Chen, Y., Usmani, S.Z., Ye, S., Qiang, W., Papanikolaou, X., Heuck, C.J., Yaccoby, S., Williams, B.O., and Van Rhee, F. (2013). Characterization of the molecular mechanism of the bone-anabolic activity of carfilzomib in multiple myeloma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074191"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1186\/s13287-020-02037-3","article-title":"ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation","volume":"11","author":"Zhang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.leukres.2014.05.022","article-title":"Carfilzomib promotes the osteogenic differentiation potential of mesenchymal stem cells derived from myeloma patients by inhibiting notch1 activity in vitro","volume":"38","author":"Li","year":"2014","journal-title":"Leuk. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1172\/JCI16198","article-title":"Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro","volume":"111","author":"Garrett","year":"2003","journal-title":"J. Clin. Invest."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3324\/haematol.2010.031302","article-title":"A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients","volume":"96","author":"Zangari","year":"2011","journal-title":"Haematologica"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1517\/14728220903025770","article-title":"Dickkopf-1: A suitable target for the management of myeloma bone disease","volume":"13","author":"Gavriatopoulou","year":"2009","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1002\/ijc.22033","article-title":"Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation","volume":"119","author":"Politou","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1056\/NEJMoa030847","article-title":"The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma","volume":"349","author":"Tian","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bone.2016.10.007","article-title":"Role and mechanism of action of sclerostin in bone","volume":"96","author":"Sato","year":"2017","journal-title":"Bone"},{"key":"ref_54","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_55","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_56","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_57","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_58","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_59","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/17474086.2019.1640115","article-title":"Monoclonal antibodies against RANKL and sclerostin for myeloma-related bone disease: Can they change the standard of care?","volume":"12","author":"Kleber","year":"2019","journal-title":"Expert Rev. Hematol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/6\/1257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:34:55Z","timestamp":1760160895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/6\/1257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,12]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cancers13061257"],"URL":"https:\/\/doi.org\/10.3390\/cancers13061257","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,12]]}}}