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 ObjectiveCenobamate 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.MethodsAdult 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.ResultsForty-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.ConclusionA 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 NumberDRKS00027568, March 2, 2022 retrospectively registered.