{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:04:32Z","timestamp":1789625072147,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007364","name":"CRT Foundations","doi-asserted-by":"publisher","award":["CRT2020"],"award-info":[{"award-number":["CRT2020"]}],"id":[{"id":"10.13039\/100007364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007364","name":"CRT Foundations","doi-asserted-by":"publisher","award":["2020BN5ZW9"],"award-info":[{"award-number":["2020BN5ZW9"]}],"id":[{"id":"10.13039\/100007364","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione Ricerca Molinette ONLUS","award":["CRT2020"],"award-info":[{"award-number":["CRT2020"]}]},{"name":"Fondazione Ricerca Molinette ONLUS","award":["2020BN5ZW9"],"award-info":[{"award-number":["2020BN5ZW9"]}]},{"name":"PRIN (CONCERTO)","award":["CRT2020"],"award-info":[{"award-number":["CRT2020"]}]},{"name":"PRIN (CONCERTO)","award":["2020BN5ZW9"],"award-info":[{"award-number":["2020BN5ZW9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>This work investigated whether the anti-resorptive drugs (ARDs) zoledronic acid (Zol) and denosumab (Dmab) affect differently the levels of circulating immune cell subsets, possibly predicting the risk of developing medication-related ONJ (MRONJ) during the first 18 months of treatment. Blood samples were collected from 10 bone metastatic breast cancer patients receiving cyclin inhibitors at 0, 6, 12, and 18 months from the beginning of Dmab or Zol treatment. Eight breast cancer patients already diagnosed with MRONJ and treated with cyclin inhibitors and ARDs were in the control group. PBMCs were isolated; the trend of circulating immune subsets during the ARD treatment was monitored, and 12 pro-inflammatory cytokines were analyzed in sera using flow cytometry. In Dmab-treated patients, activated T cells were stable or increased, as were the levels of IL-12, TNF-\u03b1, GM-CSF, IL-5, and IL-10, sustaining them. In Zol-treated patients, CD8+T cells decreased, and the level of IFN-\u03b3 was undetectable. \u03b3\u03b4T cells were not altered in Dmab-treated patients, while they dramatically decreased in Zol-treated patients. In the MRONJ control group, Zol-ONJ patients showed a reduction in activated T cells and \u03b3\u03b4T cells compared to Dmab-ONJ patients. Dmab was less immunosuppressive than Zol, not affecting \u03b3\u03b4T cells and increasing activated T cells.<\/jats:p>","DOI":"10.3390\/cells12202430","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:11:01Z","timestamp":1696990261000},"page":"2430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Denosumab and Zoledronic Acid Differently Affect Circulating Immune Subsets: A Possible Role in the Onset of MRONJ"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3029-4743","authenticated-orcid":false,"given":"Ilaria","family":"Roato","sequence":"first","affiliation":[{"name":"Bone and Dental Bioengineering Laboratory, CIR-Dental School, Department of Surgical Sciences, University of Turin, Via Nizza 230, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3885-7142","authenticated-orcid":false,"given":"Lorenzo","family":"Pavone","sequence":"additional","affiliation":[{"name":"Bone and Dental Bioengineering Laboratory, CIR-Dental School, Department of Surgical Sciences, University of Turin, Via Nizza 230, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2955-4246","authenticated-orcid":false,"given":"Riccardo","family":"Pedraza","sequence":"additional","affiliation":[{"name":"Bone and Dental Bioengineering Laboratory, CIR-Dental School, Department of Surgical Sciences, University of Turin, Via Nizza 230, 10126 Turin, Italy"},{"name":"Institute of Sciences and Technologies for Sustainable Energy and Mobility, National Council of Research, 10135 Turin, Italy"},{"name":"DIMEAS, Politecnico di Torino, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2572-6564","authenticated-orcid":false,"given":"Ilaria","family":"Bosso","sequence":"additional","affiliation":[{"name":"CIR-Dental School, Citt\u00e0 della Scienza e della Salute, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9395-4967","authenticated-orcid":false,"given":"Giacomo","family":"Baima","sequence":"additional","affiliation":[{"name":"Bone and Dental Bioengineering Laboratory, CIR-Dental School, Department of Surgical Sciences, University of Turin, Via Nizza 230, 10126 Turin, Italy"},{"name":"DIMEAS, Politecnico di Torino, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Erovigni","sequence":"additional","affiliation":[{"name":"CIR-Dental School, Citt\u00e0 della Scienza e della Salute, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5800-0749","authenticated-orcid":false,"given":"Federico","family":"Mussano","sequence":"additional","affiliation":[{"name":"Bone and Dental Bioengineering Laboratory, CIR-Dental School, Department of Surgical Sciences, University of Turin, Via Nizza 230, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons\u2019 Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J. 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