Systemic and local predictors of medication-related osteonecrosis of the jaw in patients receiving antiresorptive therapy: The Shizuoka Kokuho Database study

Bone. 2026 Jun 29;211:117993. doi: 10.1016/j.bone.2026.117993. Online ahead of print.

ABSTRACT

INTRODUCTION: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse effect of antiresorptive therapy. We aimed to identify dose-specific predictors for MRONJ risk stratification.

METHODS: We conducted a retrospective cohort study using the Shizuoka Kokuho Database, an insurance claims database. Patients ≥40 years with osteoporosis or cancer who initiated bisphosphonate or denosumab between April 2015 and September 2022 were stratified into low- and high-dose groups. The outcome was MRONJ. Candidate predictors were defined using the information available before initiation of antiresorptive therapy, including demographics, comorbidities, medications, and dental care in the preceding month (no visit, maintenance, or oral risk treatment). We estimated the subdistribution hazard ratio (SHR) and its 95% confidence interval (CI) using Fine-Gray competing risk models with all-cause mortality as the competing risk.

RESULTS: Among 104,349 patients (low-dose, 99,572; high-dose, 4777), MRONJ occurred in 148 (46.7/100,000 person-years) and 105 (2116/100,000 person-years), respectively. Oral risk treatment within 1 month before therapy initiation was associated with MRONJ in both groups (low-dose: SHR 2.99 [95% CI 1.47-6.07]); high-dose: 4.28 [2.47-7.42]). Additional predictors were anemia (1.89 [1.31-2.71]) and oral corticosteroid use (2.27 [1.43-3.62]) in the low-dose group.

CONCLUSION: Predictors of MRONJ differed between antiresorptive dose groups. Oral risk treatment immediately before therapy initiation was consistently associated with higher MRONJ occurrence, suggesting that oral risk conditions near initiation may be important for risk stratification.

PMID:42372806 | DOI:10.1016/j.bone.2026.117993