Indigenous Microbiota Protects against Inflammation-Induced Osteonecrosis

Area of Science:

• Oral microbiology
• Bone biology
• Pharmacology

Background:

• Medication-related osteonecrosis of the jaw (MRONJ) is linked to long-term therapies involving bisphosphonates and other agents.
• Pathogenic bacteria are associated with advanced MRONJ, but the role of normal oral flora remains unclear.

Purpose of the Study:

• To investigate the role of indigenous oral microbiota in the development of medication-related osteonecrosis of the jaw (MRONJ).
• To determine if oral dysbiosis exacerbates MRONJ in the presence of periodontitis and antiresorptive therapy.

Main Methods:

• Oral flora manipulation using antibiotics in mice.
• Induction of ligature-induced periodontitis (LIP) and tooth extraction.
• Histological analysis of bone necrosis, osteoclast activity, and bacterial infiltration.

Main Results:

• Normal oral flora protected against inflammation-induced osteonecrosis following tooth extraction.
• Antibiotic-induced oral dysbiosis exacerbated bone necrosis and osteoclast activity in mice with LIP and zoledronic acid treatment.
• Bacterial infiltration was increased in osteonecrosis lesions compared to healed controls.

Conclusions:

• The indigenous oral microbiota plays a protective role against medication-related osteonecrosis of the jaw.
• Oral dysbiosis, particularly in conjunction with periodontitis and antiresorptive therapy, increases the risk and severity of MRONJ.