Implant-Related Medication-related Osteonecrosis of the Jaw in Patients Receiving Bone-modifying Agent Therapy

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication associated with bone-modifying agents (BMAs). This study addresses the gap in understanding how local factors, such as peri-implantitis, extractions, surgical trauma, and timing of implant placement relative to BMA therapy, affect MRONJ development around dental implants. Materials and Methods: We conducted a retrospective analysis of 38 patients who developed peri-implant MRONJ following BMA therapy at Asan Medical Center between 2008 and 2024. Using the 2022 American Association of Oral and Maxillofacial Surgery criteria, we diagnosed and staged MRONJ. We examined the patient profiles, BMA regimens, implant placement timing, and MRONJ onset. Based on this, the subjects were divided into three groups (Group 1: implant placement before BMA administration, Group 2: implant placement after BMA administration, MRONJ occurrence within 1 year after surgery, Group 3: implant placement after BMA administration, MRONJ occurrence more than 1 year after surgery). The causes were classified as chronic inflammation (peri-implantitis) or acute inflammation (trauma caused by surgery or tooth extraction), assessed through radiographic and clinical examinations. We also observed the occurrence of MRONJ at other oral sites. Results: The cohort comprised 37 patients with osteoporosis and one patient with breast cancer. BMA treatment included oral bisphosphonates (15), intravenous bisphosphonates (7), denosumab (3), and combination therapies (13). MRONJ occurred in 21 cases (group 1, 55.2%) when implants were placed before BMA administration and in 17 cases (44.7%) when placed after administration. Among the latter, nine cases (group 2, 23.7%) developed within 1 year of implant placement, and eight cases (group 3, 21.0%) occurred more than 1 year after placement. Chronic inflammation (peri-implantitis) was the primary cause in 26 patients (68.4%), whereas acute inflammation (trauma and other local factors) was the primary cause in 12 patients (31.6%). Nine patients developed MRONJ at additional oral sites. Five cases showed MRONJ-free implants placed simultaneously with the affected implants. Conclusion: The main direct causes of MRONJ differ depending on the timing of BMA administration and implant placement. In cases with osseointegration (Groups 1 and 3), chronic inflammation was the primary cause of MRONJ, whereas acute inflammation was the main cause immediately after surgery (Group 2). Additionally, local infections and inflammation spread from adjacent tooth extractions can cause extensive lesions around MRONJ sites Conclusion: The main direct causes of MRONJ differ depending on the timing of BMA administration and implant placement. In cases with osseointegration (Groups 1 and 3), chronic inflammation was the primary cause of MRONJ, whereas acute inflammation was the main cause immediately after surgery (Group 2). Additionally, local infections and inflammation spread from adjacent tooth extractions can cause extensive lesions around MRONJ sites