Next-generation sequencing analysis of bacterial species present in the sequestrum of medication-related osteonecrosis of the jaw patients

Abstract

Objective

Antiresorptives cases of adverse reactions to highly effective drugs used to treat skeletal-related events that occur during treatment of osteoporosis or malignancy have been reported in the jaw. To date, there is no clear pathophysiology for medication-related osteonecrosis of the jaw (MRONJ), but the role of inflammation or infection has been proposed as one of several possible pathogenesis theories. This study was designed to investigate the role of infection in the pathogenesis of MRONJ by analyzing the microbial communities observed in the bone samples from MRONJ patients.

Design

Oral microbial samples were collected from 39 MRONJ patients and 45 healthy patients and subjected to next generation sequencing analysis. Alpha diversity, beta diversity, linear discriminant analysis and effect size, and network analysis were applied to compare the microbiome features.

Results

The 10 predominant microbial strains observed in MRONJ patients were Streptococcus spp. S. constellatus, Tannerella forsythia, Parvimonas micra, Granulicatella adiacens, Bacteroidaceae G-1 bacterium HMT 272, Treponema socranskii, T. maltophilum, Pyramidobacter piscolens, and Fretibacterium fastidiosum. Network analysis revealed a significant correlation between T. forsythia and P. gingivalis. T. socranskii was closely related to T. maltophilum, Fretibacterium fastidiosum, and Peptostreptococcaceae nodatum. G. adiacens was closely related to Streptococcus parasanguinis, S. sanguinis, and Prevotella buccae.

Conclusions

In conclusion, this study sheds light on the potential role of infection in the pathogenesis of MRONJ. A distinct microbial profile was identified in MRONJ patients, with notable predominance of S. constellatus, T. forsythia, P. micra and G. adiacens among others. Network analysis further revealed significant correlations between certain microbial strains, suggesting possible synergistic interactions in MRONJ pathogenesis. These findings contribute to a deeper understanding of the complex microbial dynamics underlying MRONJ and may inform future therapeutic strategies aimed at targeting specific bacterial species implicated in this condition.