{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:06:45Z","timestamp":1787677605089,"version":"build-2784847793"},"reference-count":18,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumori"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Despite Immune-Oncology (IO) combinations, bone metastases (BM) remain a clinical challenge, occurring in ~30% of metastatic renal cell carcinoma (mRCC) patients and leading to skeletal-related events (SREs). Bone-targeted therapies (BTT), denosumab (Dmab) and zoledronic acid (ZOL AC), reduce SREs but are associated with a risk of Medication-Related Osteonecrosis of the Jaw (MRONJ), especially when combined with Vascular Endothelial Growth Factor Receptor \u2013 Tyrosine Kinase Inhibitors (VEGFR-TKIs). We retrospectively collected data from mRCC patients with BM who received IO alone or in combinations and VEGFR-TKIs concurrent or sequential with BTT from January 2013 to January 2025. We identified 104 mRCC patients who received BTT (Dmab: 86\/104; ZOL AC: 18\/104; switch: 4\/104). MRONJ occurred in 12\/104 (11.5%) patients, with a median BTT exposure of 13.8 months vs. 11.6 months in the overall cohort. At ONJ diagnosis, 10\/12 patients were on VEGFR-TKI, one on IO (previously on pazopanib), and one off therapy (previously on tivozanib). Notably, patients on IO-IO or IO-TKI combinations (10) did not develop MRONJ. This study represents one of the largest real-world cohorts assessing MRONJ incidence in mRCC patients treated with VEGFR-TKIs and IO-combo with concomitant BTT. Our findings confirm an MRONJ rate consistent with prior reports (10-17%) of patients treated with TKIs monotherapy and BTT.<\/jats:p>","DOI":"10.1177\/03008916251363754","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T08:37:42Z","timestamp":1756456662000},"page":"442-446","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Medication-related jaw osteonecrosis in metastatic RCC treated with VEGFR-TKIs \u00b1 IO and bone agents: A real-world analysis"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0993-7540","authenticated-orcid":false,"given":"Marco","family":"Stellato","sequence":"first","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Zecca","sequence":"additional","affiliation":[{"name":"Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bracchi","sequence":"additional","affiliation":[{"name":"Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3978-040X","authenticated-orcid":false,"given":"Alessandro","family":"Rametta","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Claps","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Guadalupi","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9172-7003","authenticated-orcid":false,"given":"Simone","family":"Rota","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2071-8971","authenticated-orcid":false,"given":"Giuseppe","family":"Fotia","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Giannatempo","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2498-402X","authenticated-orcid":false,"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Verzoni","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.09.008"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.07.727"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1223282"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.102994"},{"key":"e_1_3_2_6_2","first-page":"2495","article-title":"New response evaluation criteria in solid tumours - Revised RECIST Guideline (version 1.1)","volume":"36","author":"Watanabe H","year":"2009","unstructured":"Watanabe H, Okada M, Kaji Y, et al. 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