[Effect of carbamazepine and valproate on bone metabolism in children with epilepsy].
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.
Song
Xiao-qing
XQ
Department of Pediatrics, Xinhua Hospital of Shanghai Second Medical University, Shanghai 200433, China.
Wang
Zhi-ping
ZP
Bao
Ke-rong
KR
Zhang
Jian-ming
JM
Wu
Jie
J
Yan
Chong-huai
CH
Shen
Xiao-ming
XM
D000596:Amino Acids / Q000652:urine; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002136:Calcium, Dietary / Q000032:analysis; D002220:Carbamazepine / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D011884:Radius / Q000000981:diagnostic imaging; D013977:Tibia / Q000000981:diagnostic imaging; D014463:Ultrasonography; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D000596:Amino Acids; D000927:Anticonvulsants; D002136:Calcium, Dietary; D015675:Osteocalcin; D002220:Carbamazepine; D014635:Valproic Acid; C036020:deoxypyridinoline