The impact of antiseizure medication on bone heath: A systematic review of animal studies

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.

Conclusion: 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.

Keywords: Antiseizure medications; Bone loss; Bone mineral density; Bone turnover markers; Preclinical; Systematic review.