Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy

Purpose: To determine whether long-term treatment with valproate (VPA) and/ or lamotrigine (LTG) in children with epilepsy is associated with altered g rowth and/or bone metabolism. Methods: Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, m ean +/- SD), with epilepsy treated with VPA and/or LTG for greater than or equal to2 years were evaluated for growth, nutrient intakes, physical activ ity, bone mineral density (BMD), and blood biochemical indices of mineral a nd bone metabolism. Results: Twenty-three (43.4%) of the children had a body height below the 1 0th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the childr en. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percen tile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0 .04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) wer e found in the inactive compared with the active group. Z-score for total b ody BMD was correlated with daily activity score (r = 0.43, p = 0.008). Pla sma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LT G-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocal cin and percentile for body height were found in the VPA-plus-LTG treatment group. Conclusions: Long-term VPA and LTG therapy, particularly when combined., is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rat her than through a direct link to the VPA and/or LTG therapy.