Yulia Novitskaya, Andreas Schulze-Bonhage, Elisa Schütz, Martin Hirsch
{"title":"加用辛奥巴酸一年抗癫痫治疗对成人耐药局灶性癫痫患者骨密度和骨转换的影响：一项观察性研究。","authors":"Yulia Novitskaya, Andreas Schulze-Bonhage, Elisa Schütz, Martin Hirsch","doi":"10.1007/s40263-024-01137-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Cenobamate is a novel anti-seizure medication (ASM) with unusually high responder rates even in patients with refractory epilepsy. Due to its enzyme-inducing properties, cenobamate could negatively affect bone metabolism, similar to other ASMs; however, effects of long-term cenobamate treatment on bone health have not yet been investigated. The aim of this longitudinal observational study was to assess the effects of 1 year of continuous, adjunctive cenobamate treatment on bone health in patients with drug-resistant, focal epilepsy.</p><p><strong>Methods: </strong>Adult patients from a tertiary epilepsy centre received cenobamate add-on to their concomitant anti-seizure medication. Bone mineral density at femoral neck and lumbar spine, as well as bone formation biomarkers, electrolytes and liver enzymes in serum were assessed at baseline and after 12 months of continuous cenobamate therapy.</p><p><strong>Results: </strong>Forty-seven patients (29 male, median age 40 years) were included in the study. Median daily dose of cenobamate at 12 months was 250 mg. Moderate, yet statistically significant reduction of the T-score at femoral neck but not lumbar spine was found after 1 year of cenobamate treatment, also in a subgroup of patients (n = 37) without enzyme inducers in the comedication. Additionally, we observed statistically significant changes in bone formation biomarkers: decreased serum level of osteocalcin and increased bone-specific alkaline phosphatase. Bone minerals (calcium and phosphorus) as well as vitamin D3 remained unchanged. Parathormone was statistically significantly reduced. There was a highly statistically significant increase in serum gamma-glutamyl transferase (GGT) levels after 12 months of treatment, reflecting an underlying hepatic enzyme induction by cenobamate.</p><p><strong>Conclusion: </strong>A statistically significant decrease of the T-score at femoral neck, as well as prominent alterations in the bone formation biomarkers, suggest an increase in bone turnover after 1 year of cenobamate treatment. The underlying mechanism is most likely attributed to the hepatic enzyme activation, indicated by a prominent elevation of serum GGT. The results alert for bone density control in susceptible patient groups.</p><p><strong>Trial registration number: </strong>DRKS00027568, March 2, 2022 retrospectively registered.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"95-106"},"PeriodicalIF":7.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695382/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effects of One-Year Anti-seizure Treatment with Add-On Cenobamate on Bone Density and Bone Turnover in Adults with Drug-Resistant Focal Epilepsy: An Observational Study.\",\"authors\":\"Yulia Novitskaya, Andreas Schulze-Bonhage, Elisa Schütz, Martin Hirsch\",\"doi\":\"10.1007/s40263-024-01137-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Cenobamate is a novel anti-seizure medication (ASM) with unusually high responder rates even in patients with refractory epilepsy. Due to its enzyme-inducing properties, cenobamate could negatively affect bone metabolism, similar to other ASMs; however, effects of long-term cenobamate treatment on bone health have not yet been investigated. The aim of this longitudinal observational study was to assess the effects of 1 year of continuous, adjunctive cenobamate treatment on bone health in patients with drug-resistant, focal epilepsy.</p><p><strong>Methods: </strong>Adult patients from a tertiary epilepsy centre received cenobamate add-on to their concomitant anti-seizure medication. Bone mineral density at femoral neck and lumbar spine, as well as bone formation biomarkers, electrolytes and liver enzymes in serum were assessed at baseline and after 12 months of continuous cenobamate therapy.</p><p><strong>Results: </strong>Forty-seven patients (29 male, median age 40 years) were included in the study. Median daily dose of cenobamate at 12 months was 250 mg. Moderate, yet statistically significant reduction of the T-score at femoral neck but not lumbar spine was found after 1 year of cenobamate treatment, also in a subgroup of patients (n = 37) without enzyme inducers in the comedication. Additionally, we observed statistically significant changes in bone formation biomarkers: decreased serum level of osteocalcin and increased bone-specific alkaline phosphatase. Bone minerals (calcium and phosphorus) as well as vitamin D3 remained unchanged. Parathormone was statistically significantly reduced. There was a highly statistically significant increase in serum gamma-glutamyl transferase (GGT) levels after 12 months of treatment, reflecting an underlying hepatic enzyme induction by cenobamate.</p><p><strong>Conclusion: </strong>A statistically significant decrease of the T-score at femoral neck, as well as prominent alterations in the bone formation biomarkers, suggest an increase in bone turnover after 1 year of cenobamate treatment. The underlying mechanism is most likely attributed to the hepatic enzyme activation, indicated by a prominent elevation of serum GGT. The results alert for bone density control in susceptible patient groups.</p><p><strong>Trial registration number: </strong>DRKS00027568, March 2, 2022 retrospectively registered.</p>\",\"PeriodicalId\":10508,\"journal\":{\"name\":\"CNS drugs\",\"volume\":\" \",\"pages\":\"95-106\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695382/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40263-024-01137-5\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40263-024-01137-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Effects of One-Year Anti-seizure Treatment with Add-On Cenobamate on Bone Density and Bone Turnover in Adults with Drug-Resistant Focal Epilepsy: An Observational Study.
Background and objective: Cenobamate is a novel anti-seizure medication (ASM) with unusually high responder rates even in patients with refractory epilepsy. Due to its enzyme-inducing properties, cenobamate could negatively affect bone metabolism, similar to other ASMs; however, effects of long-term cenobamate treatment on bone health have not yet been investigated. The aim of this longitudinal observational study was to assess the effects of 1 year of continuous, adjunctive cenobamate treatment on bone health in patients with drug-resistant, focal epilepsy.
Methods: Adult patients from a tertiary epilepsy centre received cenobamate add-on to their concomitant anti-seizure medication. Bone mineral density at femoral neck and lumbar spine, as well as bone formation biomarkers, electrolytes and liver enzymes in serum were assessed at baseline and after 12 months of continuous cenobamate therapy.
Results: Forty-seven patients (29 male, median age 40 years) were included in the study. Median daily dose of cenobamate at 12 months was 250 mg. Moderate, yet statistically significant reduction of the T-score at femoral neck but not lumbar spine was found after 1 year of cenobamate treatment, also in a subgroup of patients (n = 37) without enzyme inducers in the comedication. Additionally, we observed statistically significant changes in bone formation biomarkers: decreased serum level of osteocalcin and increased bone-specific alkaline phosphatase. Bone minerals (calcium and phosphorus) as well as vitamin D3 remained unchanged. Parathormone was statistically significantly reduced. There was a highly statistically significant increase in serum gamma-glutamyl transferase (GGT) levels after 12 months of treatment, reflecting an underlying hepatic enzyme induction by cenobamate.
Conclusion: A statistically significant decrease of the T-score at femoral neck, as well as prominent alterations in the bone formation biomarkers, suggest an increase in bone turnover after 1 year of cenobamate treatment. The underlying mechanism is most likely attributed to the hepatic enzyme activation, indicated by a prominent elevation of serum GGT. The results alert for bone density control in susceptible patient groups.
Trial registration number: DRKS00027568, March 2, 2022 retrospectively registered.
期刊介绍：
CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes:
- Overviews of contentious or emerging issues.
- Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses.
- Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
- Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry.
- Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
