{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:30:18Z","timestamp":1784759418615,"version":"3.55.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":1152,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":862,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Multiple myeloma (MM) is an incurable bone marrow cancer characterized by the development of osteolytic lesions due to the myeloma-induced increase in osteoclastogenesis and decrease in osteoblastic activity. The standard treatment of MM often involves proteasome inhibitors (PIs), which can also have a beneficial off-target bone anabolic effect. However, long-term treatment with PIs is unadvised due to their high side-effect burden and inconvenient route of administration. Ixazomib is a new-generation, oral PI that is generally well tolerated; however, its bone effect remains unknown. Here, we describe the 3-month results of a single-center phase II clinical trial investigating the effect of ixazomib treatment on bone formation and bone microstructure. Thirty patients with MM in stable disease not receiving antimyeloma treatment for \u22653\u2009months and presenting \u22652 osteolytic lesions received monthly ixazomib treatment cycles. Serum and plasma samples were collected at baseline and monthly thereafter. Sodium 18F-Fluoride positron emission tomography (NaF-PET) whole-body scans and trephine iliac crest bone biopsies were collected before and after three treatment cycles. The serum levels of bone remodeling biomarkers suggested an early ixazomib-induced decrease in bone resorption. NaF-PET scans indicated unchanged bone formation ratios; however, histological analyses of bone biopsies revealed a significant increase in bone volume per total volume after treatment. Further analyses of bone biopsies showed unchanged osteoclast number and COLL1A1High-expressing osteoblasts on bone surfaces. Next, we analyzed the superficial bone structural units (BSUs), which represent each recent microscopic bone remodeling event. Osteopontin staining revealed that following treatment, significantly more BSUs were enlarged (&amp;gt;200,000\u2009\u03bcm2), and the distribution frequency of their shape was significantly different from baseline. Overall, our data suggest that ixazomib induces overflow remodeling-based bone formation by decreasing the level of bone resorption and promoting longer bone formation events, making it a potentially valuable candidate for future maintenance treatment. \u00a9 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4807","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T03:41:25Z","timestamp":1679888485000},"page":"639-649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Increased Bone Volume by Ixazomib in Multiple Myeloma: 3-Month Results from an Open Label Phase 2 Study"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7719-6839","authenticated-orcid":false,"given":"Marta","family":"Diaz-delCastillo","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3143-1367","authenticated-orcid":false,"given":"Michael Tveden","family":"Gundesen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"},{"name":"Department of Hematology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0408-5609","authenticated-orcid":false,"given":"Christian Walther","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-9736","authenticated-orcid":false,"given":"Anne Lerberg","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4774-8393","authenticated-orcid":false,"given":"Hanne Elisabeth H\u00f8jsgaard","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Pathology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-0169","authenticated-orcid":false,"given":"Pernille Just","family":"Vinholt","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0193-2005","authenticated-orcid":false,"given":"Jon Thor","family":"Asmussen","sequence":"additional","affiliation":[{"name":"Department of Radiology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8605-9422","authenticated-orcid":false,"given":"Ida Bruun","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Hematology-Pathology Research Laboratory, Research Unit for Hematology & Research Unit for Pathology University of Southern Denmark & Odense University Hospital Odense Denmark"},{"name":"Department of Hematology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-7594","authenticated-orcid":false,"given":"Charlotte Guldborg","family":"Nyvold","sequence":"additional","affiliation":[{"name":"Hematology-Pathology Research Laboratory, Research Unit for Hematology & Research Unit for Pathology University of Southern Denmark & Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6852-2014","authenticated-orcid":false,"given":"Niels","family":"Abildgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"},{"name":"Department of Hematology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-7276","authenticated-orcid":false,"given":"Thomas","family":"Levin Andersen","sequence":"additional","affiliation":[{"name":"Department of Pathology Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"},{"name":"Department of Forensic Medicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-3780","authenticated-orcid":false,"given":"Thomas","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"},{"name":"Department of Hematology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"issue":"12","key":"2024012714110145600_jbmr4807-bib-0001","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International myeloma working group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol"},{"issue":"2","key":"2024012714110145600_jbmr4807-bib-0002","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/bmt.2009.155","article-title":"Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells","volume":"45","author":"Lioznov","year":"2010","journal-title":"Bone Marrow 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