Abstract
Objective: Data on changes in bone mineral density (BMD) from valproate (VPA) therapy are ambiguous and conflicting. Thus, the aim of this study was to systematically review the existing data and carry out a meta-analysis to investigate the effect of VPA as a monotherapy on BMD in people with epilepsy (PWE).Methods: We systematically searched PubMed, EMBASE, and MEDLINE for eligible studies. We calculated the standardized mean difference (SMD) with 95% confidence interval (CI) to investigate the statistical power of the association between VPA treatment and BMD.Results: Nineteen studies were included in this systematic review and meta-analysis. We found that BMD was lower in the VPA group than in the control group (SMD: −0.44; 95% CI: −0.65 to −0.22). A significant association was found in adult patients (SMD: −0.57; 95% CI: −0.88 to −0.26; I2 = 69.8%) and pediatric patients (SMD: −0.32; 95% CI: −0.60 to −0.03; I2 = 67.8%) by subgroup analysis. This study indicated that BMD was significantly lower in patients treated for more than 36 months than in controls (SMD: −0.52; 95% CI: −0.76 to −0.27; I2 = 61.8%). However, a significant difference was not found between patients who were treated for less than 36 months and controls (SMD: −0.36; 95% CI: −0.72 to 0.01; I2 = 74.8%).Conclusion and significance: The present study provided evidence that VPA treatment was significantly associated with BMD loss in PWE. Thus, for patients at a high risk of osteoporosis and fracture, especially for patients who need long-term treatment, VPA may not be a good choice.
Highlights
Epilepsy is one of the most common neurological disorders and is characterized by chronic and spontaneous epileptic seizures [1, 2]
There was no obvious publication bias based on the funnel plots. This result was supported by Egger’s test (P = 0.529). In this meta-analysis of 19 studies, we found a significant association between low bone mineral density (BMD) and long-term VPA therapy in people with epilepsy (PWE)
Aiming to evaluate the effect of VPA therapy on BMD in patients with epilepsy, we systematically reviewed the evidence and pooled the data of published studies that focused on the association between BMD and VPA treatment
Summary
Epilepsy is one of the most common neurological disorders and is characterized by chronic and spontaneous epileptic seizures [1, 2]. Antiepileptic drugs (AEDs) are first-line treatments for people with epilepsy (PWE) and are able to control epileptic seizures in approximately 60–70% of patients [4]. It has been reported for years that long-term AED therapy may cause adverse effects in the bone and vitamin D deficiency [5,6,7,8]. Evidence from previous studies demonstrated that old AEDs such as carbamazepine (CBZ) had large effects on bone mineral density (BMD) and the vitamin D status [10]. For PWE taking new AEDs, the abnormalities in vitamin D, calcium and BMD tended to be less severe [11, 12]
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