Anti-CD20-Mediated B Cell Depletion Is Associated With Bone Preservation in Lymphoma Patients and Bone Mass Increase in Mice

Albert Kolomansky, Irit Kaye, Nathalie Ben-Califa, Anton Gorodov, Zamzam Awida, Ofer Sadovnic, Maria Ibrahim, Tamar Liron, Sahar Hiram-Bab, Howard S. Oster, Nadav Sarid, Chava Perry, Yankel Gabet, Moshe Mittelman, Drorit Neumann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Immunotherapy with anti-CD20-specific antibodies (rituximab), has become the standard of care for B cell lymphoproliferative disorders and many autoimmune diseases. In rheumatological patients the effect of rituximab on bone mass yielded conflicting results, while in lymphoma patients it has not yet been described. Here, we used cross-sectional X-ray imaging (CT/PET-CT) to serially assess bone density in patients with follicular lymphoma receiving rituximab maintenance therapy. Remarkably, this treatment prevented the decline in bone mass observed in the control group of patients who did not receive active maintenance therapy. In accordance with these data, anti-CD20-mediated B cell depletion in normal C57BL/6J female mice led to a significant increase in bone mass, as reflected by a 7.7% increase in bone mineral density (whole femur), and a ~5% increase in cortical as well as trabecular tissue mineral density. Administration of anti-CD20 antibodies resulted in a significant decrease in osteoclastogenic signals, including RANKL, which correlated with a reduction in osteoclastogenic potential of bone marrow cells derived from B-cell-depleted animals. Taken together, our data suggest that in addition to its anti-tumor activity, anti-CD20 treatment has a favorable effect on bone mass. Our murine studies indicate that B cell depletion has a direct effect on bone remodeling.

Original languageEnglish
Article number561294
JournalFrontiers in Immunology
Volume11
DOIs
StatePublished - 19 Oct 2020

Funding

FundersFunder number
Cancer Biology Research Center
Dotan Hemato-oncology Fund
Open University of Israel
Sackler Faculty of Medicine, Tel Aviv University
Schauder Memorial Endowment Fund
Israel Science Foundation1822/12, 343/17
Tel Aviv University
Sackler Faculty of Medicine, Tel-Aviv University

    Keywords

    • anti-CD20 antibodies
    • B cell depletion
    • bone density
    • CD115
    • follicular lymphoma
    • RANKL (receptor activator for nuclear factor k B ligand)
    • rituximab

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