{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:54:15Z","timestamp":1790409255425,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Janssen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Biomarkers of bone turnover in serum are suggestive of bone dynamics during treatment in multiple myeloma (MM). We evaluated the role of daratumumab on bone remodeling among patients with relapsed\/refractory MM in the prospective, open-label, phase 2 study REBUILD. Daratumumab was administered according to the approved indication. A total of 33 out of 57 enrolled patients completed 4 months of treatment. The median percent change from baseline to 4 months in C-terminal cross-linking telopeptide of type 1 collagen (CTX) (primary endpoint) was 3.9%, with 13 (39.4%) and 11 (33.3%) patients showing at least 20% and 30% reduction in CTX levels, respectively. The median percent decrease from baseline to 4 months in tartrate resistant acid phosphatase 5b (TRACP-5b) levels (co-primary endpoint) was 2.6%, with 10 (30.3%) and 6 (18.2%) patients showing at least 20% and 30% reduction in TRACP-5b levels, respectively. However, the changes in these markers of bone catabolism were not statistically significant. Furthermore, the levels of osteocalcin, bone-specific alkaline phosphatase and procollagen type-I N-pro-peptide (bone formation markers) increased from baseline to 4 months (secondary endpoints) by 18.4%, 92.6% and 10.2%, respectively. Furthermore, the median levels of dickkopf-1 and C-C motif ligand-3 showed a significant decrease at 4 months by 17.5% and 16.0%, respectively. In conclusion, daratumumab improved bone turnover by inducing bone formation and reducing osteoblast inhibition.<\/jats:p>","DOI":"10.3390\/cancers14112768","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"2768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Daratumumab Improves Bone Turnover in Relapsed\/Refractory Multiple Myeloma; Phase 2 Study \u201cREBUILD\u201d"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-1422","authenticated-orcid":false,"given":"Evangelos","family":"Terpos","sequence":"first","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6328-9783","authenticated-orcid":false,"given":"Ioannis","family":"Ntanasis-Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-5832","authenticated-orcid":false,"given":"Efstathios","family":"Kastritis","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evdoxia","family":"Hatjiharissi","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, School of Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Katodritou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Theagenio Cancer Hospital, 54639 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Eleutherakis-Papaiakovou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-3351","authenticated-orcid":false,"given":"Evgenia","family":"Verrou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Theagenio Cancer Hospital, 54639 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gavriatopoulou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Leonidakis","sequence":"additional","affiliation":[{"name":"Health Data Specialists S.A., 11525 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriaki","family":"Manousou","sequence":"additional","affiliation":[{"name":"Health Data Specialists S.A., 11525 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sosana","family":"Delimpasi","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Unit and Department of Hematology, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Malandrakis","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Kyrtsonis","sequence":"additional","affiliation":[{"name":"First Department of Propedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Papaioannou","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, School of Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argiris","family":"Symeonidis","sequence":"additional","affiliation":[{"name":"Hematology Division, Department of Internal Medicine, School of Medicine, University of Patras, 26334 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios-Athanasios","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1097\/HS9.0000000000000045","article-title":"Long-term Outcomes in Patients With Multiple Myeloma: A Retrospective Analysis of the Dutch Population-based HAematological Registry for Observational Studies (PHAROS)","volume":"2","author":"Verelst","year":"2018","journal-title":"Hemasphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1182\/blood-2018-11-852459","article-title":"Myeloma bone 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(2021). Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed\/Refractory Multiple Myeloma: Results of the CarMMa Study. Cancers, 13.","DOI":"10.3390\/cancers13061257"},{"key":"ref_6","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_7","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. 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