Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy.
OBJECTIVE
To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism.


METHODS
Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for > or =2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism.


RESULTS
Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile 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) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma 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 LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin 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 rather than through a direct link to the VPA and/or LTG therapy.
Guo
C Y
CY
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Ronen
G M
GM
Atkinson
S A
SA
D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D001848:Bone Diseases, Developmental / Q000139:chemically induced / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage; D002648:Child; D002657:Child Development / Q000187:drug effects / Q000502:physiology; D002675:Child, Preschool; D004032:Diet / Q000706:statistics & numerical data; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006128:Growth / Q000187:drug effects*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D015675:Osteocalcin / Q000097:blood; D005082:Physical Exertion / Q000502:physiology; D014227:Triazines / Q000009:adverse effects* / Q000627:therapeutic use; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D014807:Vitamin D / Q000008:administration & dosage
D000927:Anticonvulsants; D002136:Calcium, Dietary; D014227:Triazines; D015675:Osteocalcin; D014807:Vitamin D; D014635:Valproic Acid; D000077213:Lamotrigine