{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:01:22Z","timestamp":1760234482575,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"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>Osteolytic bone disease is a hallmark of multiple myeloma (MM) mediated by MM cell proliferation, increased osteoclast activity, and suppressed osteoblast function. The proteasome inhibitor bortezomib targets MM cells and improves bone health in MM patients. Radium-223 dichloride (radium-223), the first targeted alpha therapy approved, specifically targets bone metastases, where it disrupts the activity of both tumor cells and tumor-supporting bone cells in mouse models of breast and prostate cancer bone metastasis. We hypothesized that radium-223 and bortezomib combination treatment would have additive effects on MM. In vitro experiments revealed that the combination treatment inhibited MM cell proliferation and demonstrated additive efficacy. In the systemic, syngeneic 5TGM1 mouse MM model, both bortezomib and radium-223 decreased the osteolytic lesion area, and their combination was more effective than either monotherapy alone. Bortezomib decreased the number of osteoclasts at the tumor\u2013bone interface, and the combination therapy resulted in almost complete eradication of osteoclasts. Furthermore, the combination therapy improved the incorporation of radium-223 into MM-bearing bone. Importantly, the combination therapy decreased tumor burden and restored body weights in MM mice. These results suggest that the combination of radium-223 with bortezomib could constitute a novel, effective therapy for MM and, in particular, myeloma bone disease.<\/jats:p>","DOI":"10.3390\/ijms22115570","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T13:14:21Z","timestamp":1621948461000},"page":"5570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Additive Benefits of Radium-223 Dichloride and Bortezomib Combination in a Systemic Multiple Myeloma Mouse Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-6595","authenticated-orcid":false,"given":"Mari I.","family":"Suominen","sequence":"first","affiliation":[{"name":"Pharmatest Services Oy, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenni","family":"M\u00e4ki-Jouppila","sequence":"additional","affiliation":[{"name":"Pharmatest Services Oy, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Huhtinen","sequence":"additional","affiliation":[{"name":"Aurexel Life Sciences Oy, 21240 Askainen, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Sj\u00f6holm","sequence":"additional","affiliation":[{"name":"Aurexel Life Sciences Oy, 21240 Askainen, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jukka P.","family":"Rissanen","sequence":"additional","affiliation":[{"name":"Pharmatest Services Oy, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anniina","family":"Luostarinen","sequence":"additional","affiliation":[{"name":"Pharmatest Services Oy, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja M.","family":"Fagerlund","sequence":"additional","affiliation":[{"name":"Pharmatest Services Oy, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esa","family":"Alhoniemi","sequence":"additional","affiliation":[{"name":"Vincit Oyj, 20500 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4712-0531","authenticated-orcid":false,"given":"Gerhard","family":"Siemeister","sequence":"additional","affiliation":[{"name":"Nuvisan-ICB GmbH, Therapeutic Oncology Research, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-1497","authenticated-orcid":false,"given":"Dominik","family":"Mumberg","sequence":"additional","affiliation":[{"name":"Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanna-Maria","family":"K\u00e4k\u00f6nen","sequence":"additional","affiliation":[{"name":"Aurexel Life Sciences Oy, 21240 Askainen, Finland"},{"name":"Department of Cell Biology and Anatomy, Faculty of Medicine, University of Turku, 20014 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Scholz","sequence":"additional","affiliation":[{"name":"Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"ref_1","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. 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