Evidence map›Paper›PMID 41214385›Full record

ArticleNeurology and therapy2026

Time-Dependent Effect of Anti-seizure Medications on Bone Metabolism in Patients with Epilepsy: A Cross-Sectional Study.

Bofei Chen, Jiahui Guo, Zhiruo Qiu, Beibei Shen, Yi Shi, Huali Luo, Lina Jiang, Yi Wang, Lei Chen, Ping Su and 2 more

Abstract read
In one paragraph

Article in Neurology and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Bofei ChenDepartment of Neurology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Jiahui GuoDepartment of Neurology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Zhiruo QiuDepartment of Neurology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Beibei ShenDepartment of Neurology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Yi ShiDepartment of Neurology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Huali LuoDepartment of Pathology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Lina JiangDepartment of Radiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
Yi WangKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Lei ChenDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Ping SuDepartment of Neurology, Center for Membrane Receptor and Brain Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
Xiuying ChenDepartment of Obstetrics, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, Zhejiang, China. chenxiuying2007@zju.edu.cn.
Jiajia FangDepartment of Neurology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China. fangjjiaj@zju.edu.cn.

Funding

Major science and technology projects of Zhejiang province 2023C03080the National Natural Science Foundation of China 82401698
6 · The paper itself

Abstract

introductionPatients with epilepsy (PWE) face an elevated risk of osteoporosis and bone fractures. This study aims to elucidate bone metabolic alterations in PWE and identify early detection biomarkers and contributing factors.

methodsThis cross-sectional study analyzed PWE from the Epilepsy Clinical database stratified by anti seizure medication (ASM) exposure duration. We analyzed bone turnover markers (BTMs), including 25-hydroxy vitamin D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-crosslaps (β-CTX) and β-CTX/OC ratio. The effects of epilepsy and ASMs on bone metabolism were analyzed by XGBoost model and SHapley Additive exPlanations (SHAP). Finally, we analyzed the mediation analyses assessing inflammatory pathway contributions.

resultsA total of 476 PWE were included in this study. Compared to ASM-naïve PWE, those receiving > 2 years of ASM therapy exhibited a reduced β-CTX/OC ratio (p = 0.002), while P1NP levels declined only after > 10 years of treatment (p < 0.001). Longitudinal data revealed a continued annual decline in the β-CTX/OC ratio during the 2-year follow-up period. After adjusting for confounders, longer ASM exposure duration was significantly correlated with decreased P1NP, β-CTX and β-CTX/OC ratio levels (β = - 1.74, 95% CI - 2.56 to - 0.92; p < 0.001). XGBoost-SHAP analysis identified valproic acid (VPA), oxcarbazepine (OXC) and history of status epilepticus as key contributors to β-CTX/OC ratio variability. Polytherapy had a more pronounced effect than monotherapy, particularly when levetiracetam was combined with VPA or OXC. Mediation analysis demonstrated that platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio mediate epilepsy/ASM-related bone metabolic alterations.

conclusionPWE exhibit dynamic bone metabolic alterations. Following > 2 years of ASM therapy, osteoclast inhibition precedes the onset of osteoblast dysfunction. Prolonged ASM exposure eventually reduces bone formation markers, indicating progressive impairment of osteoblastic function and a concomitant decline in bone-forming capacity. Consequently, the β-CTX/OC ratio represents a pivotal early biomarker for monitoring bone health deterioration, demonstrating significant clinical utility.

Indexed as

Anti-seizure medicationsBone turnover markersEpilepsyβ-Crosslaps/osteocalcin ratio

Identifiers

PMID41214385
PMCPMC12804518

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.