| Many studies have shown that patients taking antiepileptic drugs (AEDs) are at increased risk for metabolic bone disease and low bone mineral density. Early reports found rickets in children, but those reports were primarily in institutionalized persons. Because treatment with antiepileptic drugs (AEDs) is ofen for years or lifelong, a growing body of clinical physicians began to notice the association between AEDs and bone metabolism accompanyed the widely taking of AEDs in pediatric. The AEDs most commonly reported to cause decreased bone mineral density and disorders of bone metabolism are inducers of the hepatic enzyme (phenobarbital, phenytoin, carbamzepine). More recent studies also suggest that valporate, an hepatic enzyme inhibitor, causes abnormalities in bone metabolism. In the past 10 years, multiple new AEDs (topiramate, lamotrigine, gabapentin) have been approved. But few studies have evaluated the effect of these medications on bone metabolism. The common antiepileptic drugs used by pediatric was carbamazepine (CBZ), valproate (VPA) and topiramate (TPM). Although the association between these AEDs and bone metabolism in children was not exact, it would be affect the growth and development of children if the influence existed long time. So it is very essential that the physicians investigated the effect of the AEDs on bone metabolism and influencing mechanism. Objective: To investigate the association between carbamazepine, valproate or topiratmate and bone metabolism in children and discuss the influencing mechanism, provide a theoretical base on drawing prophylactic and therapeutic measures. Methods: The entrance standard for this study was epileptic children who hadn't received glucocorticosteroid, therapeutic dose of Vitamin D, and with no liver, renal or the other special disorders. All patients was 3~6 old years and the duration of treatment for each drug was 3~6 month. Two millitres of venous blood and ten millitres of urine at the same time (8~10AM) for each child. The samples were placed at room temperature for 2~4 hours. Then the samples were isolated by centifugation at 3000 rpm lasted 15 minutes and served in a refigerabo at -70oC. The marker of bone formation: serum alkaline phosphatase (ALP),which measured by pyrocatechol phosphate colonmetry; the marker of bone absorption: urine deoxypyridinoline (DPD), which measured by competitive enzyme immunoassay. In order to eliminate urine DPD changes with amount of urine,urine creatinine (Cr) level was presented by corrected DPD (DPD/Cr) and urine Cr were determined by cardazotic acid method. At the same time, we routinely measured plasma calcium (Ca2+) and bicarbonate (HCO3-) levelof children treated with TPM in laboratory. The data were analyzed with SPSS for windows 10.0 statistic software and presented by mean and standard difference. The difference between groups were analyzed by analysis of variance (ANOVA). The correlation-ship was analyzed by pearson method. Results: 73 children with epilepsy were enrolled in this study: 30 chlidren were treated with topiramate (TPM). 15 children were treated with carbamazepine (CBZ). 15 children were treated with valproate (VAP). 13 children without treatment as control group. The marker reflected bone formation was serum ALP (TPM 20.13±4.44U/L,CBZ 20.34±3.47U/L, VPA 17.71±2.41U/L,control group 14.75±2.41U/L). The difference of ALP between TPM treated group vs. CBZ treated group and control group was significant at the level of p<0.01. The difference of ALP between VPA treated group and control group was not significant (p>0.05). The marker reflected bone absorption was DPD/Cr (TPM 50.00±20.88nmol/mmol,CBZ 32.39 ±10.10nmol/mmol, VPA 29.84 ±13.79nmol/mmol, control group 30.81 ±6.60nmol/mmol). The difference of DPD/Cr between TPM treated group and control group was significant (p<0.05). The difference of DPD/Cr between CBZ treated group vs. VPA treated group and control group was not significant (p>0.05). The serum ALP had not significant correlation with urine DPD/Cr in each group (r=-0.083,-... |
