Denosumab and Zoledronic Acid Differently Affect Circulating Immune Subsets: A Possible Role in the Onset of MRONJ

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2023 Oct 27

PMID 37887274

Authors

Ilaria Roato

Lorenzo Pavone

Riccardo Pedraza

Ilaria Bosso

Giacomo Baima

Francesco Erovigni

Federico Mussano

Affiliations

Soon will be listed here.

Abstract

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-α, GM-CSF, IL-5, and IL-10, sustaining them. In Zol-treated patients, CD8+T cells decreased, and the level of IFN-γ was undetectable. γδT 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 γδT cells compared to Dmab-ONJ patients. Dmab was less immunosuppressive than Zol, not affecting γδT cells and increasing activated T cells.

Citing Articles

Etiopathogenesis of medication-related osteonecrosis of the jaws: a review.

Bassan Marinho Maciel G, Maciel R, Linhares Ferrazzo K, Cademartori Danesi C J Mol Med (Berl). 2024; 102(3):353-364.

PMID: 38302741 DOI: 10.1007/s00109-024-02425-9.

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