Prospective Observational Study of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma: Microbiota Profiling and Cytokine Expression
AuthorBadros, Ashraf Z
Meiller, Timothy F
Mongodin, Emmanuel F
JournalFrontiers in Oncology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractPurpose: 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/TermsCopyright © 2021 Badros, Meddeb, Weikel, Philip, Milliron, Lapidus, Hester, Goloubeva, Meiller and Mongodin.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16184
- Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw.
- Authors: Pushalkar S, Li X, Kurago Z, Ramanathapuram LV, Matsumura S, Fleisher KE, Glickman R, Yan W, Li Y, Saxena D
- Issue date: 2014 Dec
- Intravenous bisphosphonate-related osteonecrosis of the jaw: bone scintigraphy as an early indicator.
- Authors: O'Ryan FS, Khoury S, Liao W, Han MM, Hui RL, Baer D, Martin D, Liberty D, Lo JC
- Issue date: 2009 Jul
- Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review.
- Authors: Vescovi P, Nammour S
- Issue date: 2010 Apr
- Serum Markers of Bone Turnover and Angiogenesis in Patients With Bisphosphonate-Related Osteonecrosis of the Jaw After Discontinuation of Long-Term Intravenous Bisphosphonate Therapy.
- Authors: Thumbigere-Math V, Michalowicz BS, Hughes PJ, Basi DL, Tsai ML, Swenson KK, Rockwell L, Gopalakrishnan R
- Issue date: 2016 Apr
- Osteonecrosis of the jaw in Sweden associated with the oral use of bisphosphonate.
- Authors: Ulmner M, Jarnbring F, Törring O
- Issue date: 2014 Jan