{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:30:22Z","timestamp":1784759422113,"version":"3.55.0"},"reference-count":89,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Despite the increasing number of novel therapies to treat newly diagnosed multiple myeloma (NDMM), preventing skeletal-related events (SREs) remains a challenge. This review summarizes the mechanistic causes of myeloma bone disease, data supporting the use of bisphosphonates and RANKL inhibitors, and the optimal management of preventing SREs in NDMM patients. Both zoledronic acid (ZA) and denosumab are acceptable treatment options with comparable safety and efficacy profiles. However, in patients who are candidates for autologous stem cell transplant (ASCT), denosumab may be preferred over ZA due to a progression-free survival (PFS) benefit observed in post hoc analyses when used with proteasome inhibitor-based regimens. The optimal duration of bone-directed therapy is unclear, but it is typically given for two years. Supportive care should include dental evaluation at baseline, annually, and if symptoms appear, given the risk for jaw osteonecrosis with both ZA and denosumab. Both drugs should be held in the setting of dental work. Patients should receive adequate calcium and vitamin D supplementation. Supportive procedures such as cement augmentation, radiation, and orthopedic surgery can also help treat compression fractures, uncontrolled pain, cord compression, and pathologic fractures. We conclude with our approach for managing SREs and a review of novel therapies and targets.<\/jats:p>","DOI":"10.3390\/cells14161263","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T14:24:28Z","timestamp":1755267868000},"page":"1263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Preventing Skeletal-Related Events in Newly Diagnosed Multiple Myeloma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7760-5730","authenticated-orcid":false,"given":"Benjamin","family":"Massat","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Stiff","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatema","family":"Esmail","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Gauto-Mariotti","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-1667","authenticated-orcid":false,"given":"Patrick","family":"Hagen","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/j.seminoncol.2016.11.004","article-title":"Multiple myeloma epidemiology and survival: A unique malignancy","volume":"43","author":"Kazandjian","year":"2016","journal-title":"Semin. 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