Abstract：
BACKGROUND: Antiseizure medications (ASMs) are known to potentially impact bone health, but existing literature presents conflicting results regarding their specific effects on bone mineralization, metabolism, and quality.
OBJECTIVE: This systematic review aims to establish a consensus regarding the influence of ASMs on bone health based on existing preclinical studies.
METHODS: Following SYRCLE and PRISMA guidelines, we conducted a systematic search in PubMed, Science Direct, and Google Scholar to identify relevant studies. Ultimately, 21 articles were selected for inclusion in this review.
RESULTS: Among the chosen studies, approximately half involved Wistar rats as experimental subjects. Levetiracetam and sodium valproate were the most frequently investigated drugs, with a typical treatment duration of 10-12 weeks. These studies exhibited a low risk of bias in aspects like sequence generation, random housing, random outcome assessment, and reporting bias. However, blinding in performance, allocation concealment, and detection were often rated as having a high risk of bias. The collective findings suggest that prolonged ASM use leads to reduced bone mineral density, altered bone turnover marker levels (including hypovitaminosis D, hypocalcemia, and secondary hyperparathyroidism), deterioration of bone microarchitecture, and decreased mechanical strength.
CONCLUSIONS: The adverse effects on bone associated with ASMs are not limited to enzyme-inducing drugs, as newer generation ASMs may also contribute to these effects. Hypovitaminosis D alone may not be solely responsible for ASM-induced bone issues, suggesting the involvement of other mechanisms. Furthermore, substantial variations were observed in the results of different preclinical studies on individual ASMs, highlighting the need to standardize animal study methodologies to enhance reproducibility and reduce variation.
OBJECTIVE: This systematic review aims to establish a consensus regarding the influence of ASMs on bone health based on existing preclinical studies.
METHODS: Following SYRCLE and PRISMA guidelines, we conducted a systematic search in PubMed, Science Direct, and Google Scholar to identify relevant studies. Ultimately, 21 articles were selected for inclusion in this review.
RESULTS: Among the chosen studies, approximately half involved Wistar rats as experimental subjects. Levetiracetam and sodium valproate were the most frequently investigated drugs, with a typical treatment duration of 10-12 weeks. These studies exhibited a low risk of bias in aspects like sequence generation, random housing, random outcome assessment, and reporting bias. However, blinding in performance, allocation concealment, and detection were often rated as having a high risk of bias. The collective findings suggest that prolonged ASM use leads to reduced bone mineral density, altered bone turnover marker levels (including hypovitaminosis D, hypocalcemia, and secondary hyperparathyroidism), deterioration of bone microarchitecture, and decreased mechanical strength.
CONCLUSIONS: The adverse effects on bone associated with ASMs are not limited to enzyme-inducing drugs, as newer generation ASMs may also contribute to these effects. Hypovitaminosis D alone may not be solely responsible for ASM-induced bone issues, suggesting the involvement of other mechanisms. Furthermore, substantial variations were observed in the results of different preclinical studies on individual ASMs, highlighting the need to standardize animal study methodologies to enhance reproducibility and reduce variation.
摘要：
背景：已知抗癫痫药物（ASM）可能会影响骨骼健康，但是现有的文献提出了关于它们对骨矿化的具体影响的相互矛盾的结果，新陈代谢，和质量。
目的：本系统综述旨在基于现有的临床前研究，就ASM对骨骼健康的影响达成共识。
方法：遵循SYRCLE和PRISMA指南，我们在PubMed进行了系统的搜索,科学直接，和谷歌学者确定相关研究。最终,本综述选择了21篇文章。
结果：在选定的研究中，大约一半以Wistar大鼠为实验对象。左乙拉西坦和丙戊酸钠是最常见的研究药物，典型的治疗持续时间为10-12周。这些研究在序列生成等方面表现出较低的偏倚风险，随机住房，随机结果评估，和报告偏见。然而,在性能上致盲，分配隐藏，并且检测通常被认为具有高偏倚风险.集体发现表明，长期使用ASM会导致骨矿物质密度降低，骨转换标志物水平改变(包括维生素D缺乏症，低钙血症,和继发性甲状旁腺功能亢进)，骨微结构的恶化，机械强度下降。
结论：与ASM相关的对骨骼的不良反应不仅限于酶诱导药物，因为新一代ASM也可能对这些影响有贡献。单独的维生素D缺乏可能不是ASM引起的骨骼问题的唯一原因，暗示其他机制的参与。此外，在对个体ASM的不同临床前研究的结果中观察到了很大的差异，强调需要标准化动物研究方法，以提高可重复性和减少变异。
目的：本系统综述旨在基于现有的临床前研究，就ASM对骨骼健康的影响达成共识。
方法：遵循SYRCLE和PRISMA指南，我们在PubMed进行了系统的搜索,科学直接，和谷歌学者确定相关研究。最终,本综述选择了21篇文章。
结果：在选定的研究中，大约一半以Wistar大鼠为实验对象。左乙拉西坦和丙戊酸钠是最常见的研究药物，典型的治疗持续时间为10-12周。这些研究在序列生成等方面表现出较低的偏倚风险，随机住房，随机结果评估，和报告偏见。然而,在性能上致盲，分配隐藏，并且检测通常被认为具有高偏倚风险.集体发现表明，长期使用ASM会导致骨矿物质密度降低，骨转换标志物水平改变(包括维生素D缺乏症，低钙血症,和继发性甲状旁腺功能亢进)，骨微结构的恶化，机械强度下降。
结论：与ASM相关的对骨骼的不良反应不仅限于酶诱导药物，因为新一代ASM也可能对这些影响有贡献。单独的维生素D缺乏可能不是ASM引起的骨骼问题的唯一原因，暗示其他机制的参与。此外，在对个体ASM的不同临床前研究的结果中观察到了很大的差异，强调需要标准化动物研究方法，以提高可重复性和减少变异。
