Association between periodontal disease severity and the risk of medication-related osteonecrosis of the jaw: a systematic review and meta-analysis by the Korean Academy of Periodontology.

PURPOSE: This systematic review and meta-analysis quantitatively synthesized the available evidence on the association between periodontal disease (PD) and the risk of medication-related osteonecrosis of the jaw (MRONJ). We also examined whether MRONJ risk varied according to PD severity among patients receiving antiresorptive or antiangiogenic therapy. METHODS: MEDLINE, Web of Science, Embase, Scopus, and Google Scholar were comprehensively searched for studies published through November 30, 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies were required to provide a reproducible definition of PD based on clinical, radiographic, guideline-based, or predefined administrative-code criteria. Studies relying on non-operationalized clinical labels without sufficient diagnostic detail were excluded. A random-effects meta-analysis was performed using log-transformed relative-effect estimates and their standard errors. To address heterogeneity in exposure definitions, studies were stratified into a severe/procedure-linked group and a moderate-to-mixed group. RESULTS: Eight observational studies met the eligibility criteria and were included in the quantitative synthesis. The primary meta-analysis showed a statistically significant association between PD and MRONJ, indicating that patients with PD had an approximately threefold higher risk of developing MRONJ than those without PD (pooled relative-effect estimate, 3.02; 95% confidence interval [CI], 1.99-4.56). In subgroup analyses, the severe/procedure-linked group had a higher pooled relative-effect estimate (4.26; 95% CI, 1.96-9.24) than the moderate-to-mixed group (2.39; 95% CI, 1.45-3.94). However, the between-subgroup difference was not statistically significant; therefore, the subgroup findings should be interpreted as exploratory. CONCLUSIONS: Current evidence supports an association between PD and increased MRONJ risk in patients receiving antiresorptive or antiangiogenic therapy. Although the subgroup findings suggest that more advanced periodontal breakdown may be associated with greater risk, this severity-based pattern should be interpreted cautiously and confirmed in future studies with larger sample sizes and standardized diagnostic criteria.