He Dongdong, Di Jingkai, Jiang Peirui, Liu Lujia, Wang Feida, Xiang Chuan
Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, China.
Shanxi Provincial Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, China.
CNS Neurosci Ther. 2025 Sep;31(9):e70612. doi: 10.1111/cns.70612.
Dimethyl fumarate (DMF) is currently recommended as a first-line therapy for multiple sclerosis (MS). Investigating its adverse events (AEs) holds significant clinical importance. This study aimed to explore the association between DMF and fracture-related AEs.
Data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024) were analyzed using disproportionality analysis. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM) were employed to identify and characterize AEs. Age- and gender-specific subgroup analyses were conducted to evaluate AE patterns. Additionally, Weibull distribution analysis was performed to assess the temporal relationship of AE onset.
Overall, spinal fusion fracture (ROR = 13.13, 95% CI: 1.73-99.86) and coccyx fracture (ROR = 3.05, 95% CI: 1.92-4.86) exhibited the strongest signals. Gender and age heterogeneity were observed in DMF-associated fracture risks. Female patients showed the highest signals for spinal fusion bone fracture (ROR = 13.13) and coccyx fracture (ROR = 2.80), while males predominantly exhibited patella (ROR = 4.94) and scapula fractures (ROR = 3.68). Age stratification revealed elevated risks of forearm fracture (ROR = 10.29, 95% CI: 4.24-24.96) and ankle fracture (ROR = 5.63, 95% CI: 4.32-7.35) in elderly patients, whereas younger populations displayed diverse multi-site fractures. Time-to-onset (TTO) analysis indicated that 63.62% of fractures occurred within the first 2 years of the treatment cycle, with a median onset time of 506 days. Weibull distribution modeling indicated that DMF's failure pattern aligned with an early failure-type curve.
DMF use is associated with an increased risk of fracture-related AEs, with demographic variations in susceptibility. This study provides critical insights into the safety profile of DMF in MS management, underscoring the need for vigilance in high-risk populations.
富马酸二甲酯（DMF）目前被推荐作为多发性硬化症（MS）的一线治疗药物。研究其不良事件（AE）具有重要的临床意义。本研究旨在探讨DMF与骨折相关不良事件之间的关联。
使用不成比例分析对美国食品药品监督管理局不良事件报告系统（FAERS）数据库（2004年第一季度至2024年第三季度）的数据进行分析。采用报告比值比（ROR）、比例报告比值比（PRR）、信息成分（IC）和经验贝叶斯几何均值（EBGM）来识别和描述不良事件。进行年龄和性别特异性亚组分析以评估不良事件模式。此外，进行威布尔分布分析以评估不良事件发生的时间关系。
总体而言，脊柱融合骨折（ROR = 13.13，95%置信区间：1.73 - 99.86）和尾骨骨折（ROR = 3.05，95%置信区间：1.92 - 4.86）显示出最强的信号。在DMF相关骨折风险中观察到性别和年龄异质性。女性患者脊柱融合骨折（ROR = 13.13）和尾骨骨折（ROR = 2.80）的信号最强，而男性主要表现为髌骨骨折（ROR = 4.94）和肩胛骨骨折（ROR = 3.68）。年龄分层显示老年患者前臂骨折（ROR = 10.29，95%置信区间：4.24 - 24.96）和踝关节骨折（ROR = 5.63，95%置信区间：4.32 - 7.35）风险升高，而年轻人群表现出多种不同部位的骨折。发病时间（TTO）分析表明，63.62%的骨折发生在治疗周期的前2年内，中位发病时间为506天。威布尔分布模型表明，DMF的失效模式符合早期失效型曲线。
使用DMF与骨折相关不良事件风险增加有关，且易感性存在人口统计学差异。本研究为DMF在MS治疗中的安全性概况提供了关键见解，强调了对高危人群保持警惕的必要性。
