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    Prospective Observational Study of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma: Microbiota Profiling and Cytokine Expression

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    Author
    Badros, Ashraf Z
    Meddeb, Mariam
    Weikel, Dianna
    Philip, Sunita
    Milliron, Todd
    Lapidus, Rena
    Hester, Lisa
    Goloubeva, Olga
    Meiller, Timothy F
    Mongodin, Emmanuel F
    Date
    2021-06-24
    Journal
    Frontiers in Oncology
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fonc.2021.704722
    Abstract
    Purpose: Define incidence and risk factors of osteonecrosis of the jaw (ONJ) and explore oral microbial signatures and host immune response as reflected by cytokine changes in saliva and serum in multiple myeloma (MM) patients on bisphosphate (BP) therapy. Patients and Methods: A single center observational prospective study of MM patients (n = 110) on >2 years of BP, none had ONJ at enrollment. Patients were followed every 3 months for 18 months with clinical/dental examination and serial measurements of inflammatory cytokines, bone turnover markers, and angiogenic growth factors. Oral microbiota was characterized by sequencing of 16S rRNA gene from saliva. Results: Over the study period 14 patients (13%) developed BRONJ, at a median of 5.7 years (95% CI: 1.9–12.0) from MM diagnosis. Chronic periodontal disease was the main clinically observed risk factor. Oral microbial profiling revealed lower bacterial richness/diversity in BRONJ. Streptococcus intermedius, S. mutans, and S. perioris were abundant in controls; S. sonstellatus and S anginosus were prevalent in BRONJ. In the saliva, at baseline patients who developed BRONJ had higher levels of MIP-1β; TNF-α and IL-6 compared to those without BRONJ, cytokine profile consistent with M-1 macrophage activation. In the serum, patients with BRONJ have significantly lower levels of TGF beta and VEGF over the study period. Conclusion: Periodontal disease associated with low microbial diversity and predominance of invasive species with a proinflammatory cytokine profile leading to tissue damage and alteration of immunity seems to be the main culprit in pathogenesis of BRONJ.
    Rights/Terms
    Copyright © 2021 Badros, Meddeb, Weikel, Philip, Milliron, Lapidus, Hester, Goloubeva, Meiller and Mongodin.
    Keyword
    bisphosphanates
    cytokines
    microbiome
    multiple myeloma
    osteonecrosis of the jaw
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16184
    ae974a485f413a2113503eed53cd6c53
    10.3389/fonc.2021.704722
    Scopus Count
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