Risk factors for denosumab-related osteonecrosis of the jaw: a pharmacovigilance study using the U.S. FDA adverse event reporting system database

作者：Hehe Bai, Jinping Wang, Xiaonian Han, Huan Li, Xiaojing Nie, Guan Wang · 发表于：Frontiers in Endocrinology · 年份：2025 · DOI：10.3389/fendo.2025.1586626 · 被引用次数：2 · 研究领域：Bone health and treatments、Parathyroid Disorders and Treatments、Bone and Joint Diseases

Objective This study aims to comprehensively evaluate risk factors for denosumab-related osteonecrosis of the jaw (ONJ), focusing on dosage, concomitant medications, and patient demographics, to inform clinical decision-making and optimize therapeutic strategies. Methods A retrospective pharmacovigilance analysis was conducted using data from the US FDA Adverse Event Reporting System (FAERS) spanning Q2–2010 to Q3 2024. Disproportionality analysis, logistic regression analysis, and time-to-onset analysis were employed to assess the association between denosumab use and ONJ. Key variables included dosage (60 mg Q6m vs . 120 mg Q4w), concomitant medications (e.g., bisphosphonates, glucocorticoids, chemotherapies), and patient demographics (age, sex). Results Among 7,689 denosumab-related ONJ cases, the 120 mg dose demonstrated markedly higher ONJ risk (reporting odds ratio [ROR] = 245.47 vs . 28.59 for 60 mg; P < 0.001), with a 54-day shorter median onset time (452 vs . 506 days; P = 0.011). Combination therapies synergistically amplified risk, with sequential administration of zoledronic acid yielding the highest ROR at 726.43 (95% CI: 642.83–820.90) and an accelerated time to onset (median 378 days vs . 462 days for monotherapy). Multivariate logistic regression confirmed age ≥65 years (adjusted odds ratio [aOR] = 1.48), high-dose denosumab (aOR = 7.18), and concomitant medications (e.g., bisphosphonates, glucocorticoids, chemotherapies) as independent risk factors. Ma...