Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA.
Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
Bone. 2021 Aug;149:115996. doi: 10.1016/j.bone.2021.115996. Epub 2021 May 5.
Anti-seizure medication (ASM) is necessary to manage epilepsy and often prescribed to children and adolescents, but can lead to iatrogenic effects, including bone fragility by altering bone metabolism. Disrupting bone metabolism during crucial developmental stages could have a lasting adverse effect on bone health. Therefore, the objective of this propensity score-matched, observational cohort study was to determine if age when initiating ASM therapy across developmental stages (from pre- to post-puberty) for individuals with epilepsy was associated with an increased risk of fragility fracture.
Data from 01/01/2011 to 12/31/2018 were extracted from Optum Clinformatics® Data Mart. Children aged 4-21 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline and 4-years of follow-up. The primary group of interest included new ASM users (i.e., treatment naïve) with epilepsy. The comparison group, no ASM users without epilepsy, was matched 1:14 to new ASM users with epilepsy for demographics and baseline fracture. To provide a proxy for developmental stages, age was categorized as 4-6 (pre-puberty), 7-10 (early puberty), 11-13 (mid-puberty), 14-17 (late puberty), and 18-21 (post-puberty). Crude incidence rate (IR; per 1000 person years) and IR ratio (IRR and 95% confidence intervals [CI]) were estimated for non-trauma fracture (NTFx) for up to 4-years of follow-up.
Prior to stratifying by age group, the crude NTFx IR (95% CI) of 20.6 (16.5-24.8) for new ASM users with epilepsy (n = 1205) was 34% higher (IRR = 1.34; 95% CI = 1.09-1.66) than the crude NTFx IR (95% CI) of 15.4 (14.4-16.3) for no ASM users without epilepsy. The groups exhibited a different pattern of NTFx incidence with age, with new ASM users showing a more dramatic increase and peaking at 11-13 years, then decreasing with the older age groups. The crude IR and IRR were elevated for new ASM users with epilepsy compared to no ASM users without epilepsy for each age group (10% to 55% higher), but was only statistically significant for 11-13 years (IRR = 1.55; 95% CI = 1.02-2.36).
Children with epilepsy initiating ASM therapy may be vulnerable to fragility fracture, especially when initiating ASM around the time of puberty. Clinicians should be aware of this age-related association and consider age-appropriate adjunct bone fragility therapies.
抗癫痫药物（ASM）是治疗癫痫所必需的，通常开给儿童和青少年，但会导致医源性影响，包括通过改变骨代谢导致骨脆弱。在关键的发育阶段扰乱骨代谢可能会对骨骼健康产生持久的不良影响。因此，本倾向评分匹配的观察性队列研究的目的是确定在个体癫痫的各个发育阶段（从青春期前到青春期后）开始 ASM 治疗的年龄是否与脆性骨折风险增加相关。
从 2011 年 1 月 1 日至 2018 年 12 月 31 日，从 Optum Clinformatics®Data Mart 中提取数据。纳入基线时年龄为 4-21 岁且至少有 5 年连续健康计划入组的儿童，以允许 1 年的基线和 4 年的随访。主要感兴趣的组包括新的 ASM 使用者（即无治疗史）癫痫患者。无癫痫的新 ASM 使用者按 1:14 匹配无 ASM 使用者作为对照组，以匹配人口统计学和基线骨折情况。为了提供发育阶段的代理，年龄分为 4-6 岁（青春期前）、7-10 岁（早期青春期）、11-13 岁（中期青春期）、14-17 岁（晚期青春期）和 18-21 岁（青春期后）。在长达 4 年的随访中，估算非创伤性骨折（NTFx）的粗发病率（IR；每 1000 人年）和 IR 比（IRR 和 95%置信区间 [CI]）。
在按年龄组分层之前，新 ASM 使用者癫痫患者（n=1205）的粗 NTFx IR（95%CI）为 20.6（16.5-24.8），比无癫痫的新 ASM 使用者无 ASM 使用者（n=1205）的粗 NTFx IR（95%CI）高 34%（IRR=1.34；95%CI=1.09-1.66）。两组的 NTFx 发病率随年龄表现出不同的模式，新 ASM 使用者的发病率急剧上升，在 11-13 岁时达到峰值，然后随年龄组的增加而下降。与无 ASM 使用者相比，新 ASM 使用者的癫痫患者的粗 IR 和 IRR 均升高（10%至 55%），但仅在 11-13 岁时具有统计学意义（IRR=1.55；95%CI=1.02-2.36）。
开始 ASM 治疗的癫痫儿童可能容易发生脆性骨折，尤其是在青春期开始时开始 ASM 治疗时。临床医生应该意识到这种与年龄相关的关联，并考虑使用适合年龄的骨脆弱性辅助治疗。
