[Effect of carbamazepine and valproate on bone metabolism in children with epilepsy]
Xiao-qing Song1, Zhi-ping Wang, Ke-rong Bao
1Department of Pediatrics, Xinhua Hospital of Shanghai Second Medical University, Shanghai 200433, China.
Insights
Long-term use of anti-epileptic drugs like carbamazepine or valproate in children is linked to reduced bone mineral density (BMD). Low calcium intake and higher BMI worsen bone health, necessitating supplementation.
Area of Science:
- Pediatric Endocrinology
- Neurology
- Metabolic Bone Disease
Background:
- Epilepsy affects children, with treatments potentially impacting bone health.
- Long-term use of antiepileptic drugs (AEDs) like carbamazepine (CBZ) and valproate (VPA) requires monitoring for adverse effects.
- Bone metabolism abnormalities can occur in children on chronic AED therapy.
Purpose of the Study:
- To evaluate bone health in epileptic children treated with CBZ or VPA using quantitative ultrasound (QUS).
- To assess biochemical markers of bone metabolism in these children.
- To propose strategies for improving the quality of life for epileptic children by addressing bone health.
Main Methods:
- Ninety-two epileptic children on CBZ or VPA for over two years were assessed for bone mineral density (BMD) via QUS.
- Biochemical markers including serum osteocalcin (OC) and urine deoxypyridinoline (DPD), along with daily calcium intake, were measured.
- Thirty-five healthy children served as controls; reduced BMD was defined by Z scores below -0.7.
Main Results:
- Epileptic children showed significantly reduced BMD compared to controls, with a negative correlation between AED duration and BMD.
- Serum OC levels were significantly lower in epileptic children, particularly those on VPA, while DPD levels varied.
- Reduced BMD was associated with longer AED treatment duration (>5 years), higher BMI, and lower calcium intake.
Conclusions:
- Long-term CBZ or VPA use is associated with impaired bone metabolism, characterized by reduced BMD and decreased bone formation.
- Extended AED therapy is a key factor in poor bone health in epileptic children, exacerbated by low calcium intake and high BMI.
- QUS is effective for monitoring BMD in children on long-term AEDs; calcium and vitamin D supplementation may improve bone health and quality of life.
Objective:
To assess bone health in epileptic children who have been treated with carbamazepine (CBZ) or valproate (VPA) by using quantitative ultrasound (QUS) and determining the biochemical indices of bone metabolism, and to provide a proposal to improve quality of life of epileptic children.
Methods:
Ninety-two epileptic children who had been treated with CBZ or VPA for more than two years were evaluated for bone mineral density (BMD) at the mid-shaft tibia and the distal third of the radius. Biochemical indices of bone metabolism including urine deoxypyridinoline (DPD) and serum osteocalcin (OC), and daily calcium intake were also evaluated. Thirty-five age-matched healthy children were used as controls. Reduced BMD was defined as speed of sound (SOS) Z scores of the mid-shaft tibia and (or) the distal third of the radius less than -0.7.
Results:
BMD was reduced in epileptic children significantly when compared to the controls (P < 0.05). In addition, a negative correlation was found between the duration of anti-epileptic drugs (AEDs) use and BMD (r(s) = -0.21 - -0.31, P < 0.05), the lowest BMD was observed in those who had been treated for the longest time. The serum values of OC in epileptic children were significantly reduced relative to the controls (P < 0.01), children who took VPA had the lowest value of OC. However, the urine values of DPD showed no significant difference between epileptic and healthy children (P > 0.05); children who took CBZ had the highest value of DPD. Thirty-two epileptic children (35%) and five (14%) sex- and age-matched healthy children had reduced BMD, significant difference was found between them (P < 0.05). Moreover, epileptic children with reduced BMD seemed to have higher body mass index (BMI) (P < 0.05), take less daily calcium intake (P < 0.01), and had longer duration of AEDs (P < 0.01). The two risk factors of having reduced BMD in epileptic children were those who had been treated with AEDs for more than five years and higher BMI, while the protective factor was daily calcium intake.
Conclusions:
Long-term use of CBZ or VPA is associated with bone metabolism abnormalities, which include reduced BMD and decreased bone turnover (mainly decreased bone formation). Long-term anti-epileptic therapy is an important factor for impaired bone health in epileptic children, and that low calcium intake and high BMI could be two aggravating factors. QUS is a useful method to evaluate BMD of epileptic children who are on long-term anti-epileptic therapy, and to recognize the status of bone health, in helping to promote bone health and improve quality of life in epileptic children by the use of calcium and vitamin D supplementation.
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