Role of Actinomyces spp. and related organisms in the development of medication-related osteonecrosis of the jaw (MRONJ): Clinical evidence based on a case series.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common consequence of antiresorptive treatment, which often leads to the development of necrotic exposed bone surfaces with inflammatory processes affecting the jawbone. Although the development of MRONJ is often associated with the inflammatory response or infections caused by the colonizing members of the oral microbiota, the exact pathogenesis of MRONJ is still not fully understood. In the present paper, we aimed to provide additional, microbiological culture-supported evidence, supporting the "infection hypothesis" that Actinomyces spp. and related organisms may play an important pathogenic role in the development of MRONJ and the resulting bone necrosis. In our case series, all patients presented with similar underlying conditions and anamnestic data, and have received antiresorptive medications (bisphosphonates or a RANK ligand (RANKL) inhibitor) to prevent the occurrence or progression of bone metastases, secondary to prostate cancer. Nevertheless, a few years into antiresorptive drug therapy, varying stages of MRONJ was identified in the mentioned patients. In all three cases, quantitative microbiological culture of the necrotic bone samples yielded a complex microbiota, dominated by Actinomyces and Schaalia spp. with high colony counts. Additionally, our followed-up case series document the treatment of these patients with a combination of surgical intervention and long-term antibiotic therapy, where favourable clinical responses were seen is all cases. If the "infection hypothesis" is valid, it may have significant consequences in the preventative and therapeutic strategies associated with this disease.