Cumulative antiresorptive exposure and dentoalveolar procedures increase medication-related osteonecrosis of the jaw risk in U.S. veterans treated for fracture prevention.

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious complication of bisphosphonate (BP) or denosumab therapy. Prior studies evaluating MRONJ risk factors largely involve cancer populations, small samples, claims-based data, or limited covariate assessment. We sought to determine MRONJ risk factors among patients receiving antiresorptives for osteoporosis. A retrospective cohort study of adults ≥50 years in the U.S. Veterans Health Administration with comprehensive dental benefits prescribed ≥1 oral (alendronate, risedronate, ibandronate) or intravenous (zoledronic acid, ibandronate) BP or denosumab between 10/1/1999-12/31/2022 was performed. Individuals with non-osteoporosis indications or dosing regimens, other BP or anabolic osteoporosis medication use, or missing covariates were excluded. Demographics, clinical characteristics, and medications were determined. Invasive dentoalveolar procedures were ascertained using Current Dental Terminology codes. Natural language processing of electronic medical records identified MRONJ events through 12/31/2023. Cox models estimated hazard ratios (HRs). Baseline characteristics were fixed, while comorbidities, medications (including cumulative antiresorptive exposure), and dental procedures were modeled as time-varying, updated at 90-day intervals. Among 42,378 Veterans contributing 381,437 person-years, 44 developed MRONJ. Cumulative 20-year MRONJ incidence was 0.18% (95% confidence interval (CI): 0.13-0.25%). In multivariable-adjusted analyses, Multiracial versus White race (HR: 5.47; 95% CI: 1.31-22.91), baseline body mass index (HR: 0.89 per 1 kg/m² increase; 95% CI: 0.84-0.96), cumulative antiresorptive exposure (HR: 1.34 per 1-year increase; 95% CI: 1.15-1.56), and recent invasive dentoalveolar procedure (HR: 4.40; 95% CI: 1.70-11.38) were independently associated with MRONJ. MRONJ incidence was very low among patients receiving antiresorptives for osteoporosis, although associations of cumulative antiresorptive exposure and dentoalveolar procedures with MRONJ risk may inform shared decision-making.