Possible Contribution of Oral Microbiota in the Osteonecrosis of the Jaw Induced by Zoledronate or Denosumab: A Preliminary Study

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a clinically significant side effect related to antiresorptive therapies, such as denosumab and bisphosphonates. MRONJ may develop following oral surgical procedures or spontaneously. Although the pathophysiological processes underlying MRONJ are not well clarified, infections, commonly occurring after oral surgery, seem to have an important contribution in its development. Consequently, the role of the oral microbiota warrants investigation. This study investigates the possible contribution of the salivary microbiota to the onset of osteonecrosis in subjects treated with zoledronate or denosumab. Methods: Three groups of subjects were analyzed: patients treated with zoledronate or denosumab who had developed MRONJ (cases); those who did not (controls) and healthy subjects. Oral microbioma was evaluated through next-generation sequencing. Results: A total of 55 individuals were enrolled: 16 healthy subjects (29.1%), 21 controls (38.2%), and 18 cases (32.7%). Differences in the abundance of certain bacterial taxa were observed both among the three groups and in pairwise comparisons. Furthermore, a cut-off value of 5.51% for Streptococcus spp. was identified as being associated with the development of MRONJ. Conclusions: For the first time, this preliminary study highlights differences in the salivary microbiota among healthy subjects, controls, and cases, suggesting a potential cut-off value for Streptococcus spp. Despite the limited sample size, these findings provide initial insights. Further studies in larger cohorts are warranted.