Premature Occlusal Contacts Induce MRONJ in Osseointegrated Dental Implants: An Experimental In Vivo Study

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating condition associated with antiresorptive agents (ARAs) and can occur around well-osseointegrated dental implants. Although implant presence-triggered osteonecrosis (IPTO) has been primarily linked to bacteria-related peri-implantitis, whether occlusal trauma contributes to IPTO remains unclear. Therefore, this study developed a novel premature occlusal contact (POC) mouse implant model to evaluate the effect of occlusal trauma on MRONJ development around osseointegrated implants. MATERIAL AND METHODS: Eighteen mice underwent bilateral maxillary first molar extraction followed by immediate implant placement. After a 3-week healing period to allow osseointegration, mice were randomized to receive intravenous zoledronic acid (ZOL, 125 μg/kg) or saline vehicle (Veh) twice weekly (n = 9 per group). One week later, POC was induced in a split-mouth design by applying composite resin to one implant, whereas the contralateral implant served as a control. After 5 weeks of occlusal loading, mice were euthanized for μCT and histological analyses. RESULTS: μCT analysis revealed that POC reduced radiographic bone-to-implant contact (rBIC) in both Veh- and ZOL-treated mice. POC significantly increased empty lacunae around the implant neck in Veh-treated mice, whereas in ZOL-treated mice, POC induced extensive circumferential bone necrosis around the implant, accompanied by increased macrophage infiltration. No significant differences in peptidoglycan (PGN)-positive signals were observed among the experimental groups. CONCLUSION: These findings suggest that POC contributes to peri-implant osteonecrosis under ZOL treatment, supporting occlusal trauma as an important local factor in MRONJ development around osseointegrated dental implants.