Effect of new antiepileptic drugs on bone metabolism in children:a Meta-analysis / 中国医师进修杂志

Objective To systematically evaluate the effects of new antiepileptic drugs on bone metabolism in children. Methods Chinese and English databases such as Pubmed, Cochrance Library, China Knowledge Network, Wanfang Knowledge Service Platform, and Weipu Chinese Journal Full-text Database were searched. The search time was limited for each database from the first issue to August 2018, and new anti-epileptic clinical trial of the effects of drugs on bone metabolism in children was selected. The literature was independently read by two reviewers. The effect size was extracted according to the inclusion and exclusion criteria, and the quality of the study was evaluated. The system evaluation (Meta analysis) was performed using Revman 5.3 software. Results A total of 526 cases in the experimental group (children taking antiepileptic drugs) and 478 cases in the control group (healthy children or children without taking antiepileptic drugs) were included in 16 pieces of literatures. Meta-analysis showed that there was no significant difference in bone mineral density between experimental group and control group ( SMD＝-0.03, 95% CI :-0.17-0.10, P＝0.62). As for bone turnover markers, there was significant differences in serum total alkaline phosphatase (ALP) between the two groups ( SMD＝0.19, 95% CI : 0.03- 0.36, P＝0.02), while there were no significant differences in serum calcium, serum phosphorus, serum bone specific alkaline phosphatase, serum vitamin D and the ratio of deoxypyridinoline andcreatinine (DPD/Cr). Conclusions The new antiepileptic drugs have no effect on bone mineral density. In the aspect of bone turnover markers, the serum total alkaline phosphatase of the children taking the new antiepileptic drugs is higher, but has no effect on other bone turnover markers.

New antiepileptic drugs

Epilepsy is one of the most common chronic neurologic conditions. Pharmacologic therapy is by far the most common approach, with the other modalities typically limited to patients with pharmacoresistant epilepsies. A host of new antiepileptic drugs (AEDs) have been introduced over the last 20 years. The AEDs including the conventional ones are more or less equally effective in patients with partial epilepsy. Therefore, relative efficacy is not a useful factor in selecting a particular drug. A conventional AED, valproic acid is regarded as having superior efficacy than the other broad-spectrum AEDs including new ones in patients with generalized epilepsy. However, it can have considerable side effects, such as reproductive dysfunction and teratogenicity to young women with epilepsy. One of the clearest advantages of many new AEDs over the conventional ones has been their more favorable pharmacokinetic and drug-drug interaction profiles compared with the conventional ones involved in the cytochrome P450 enzymatic system, which may change the levels of other antiepileptic and nonantiepileptic drugs, and endogenous substances. Many new AEDs have unique mechanisms of action and slightly better tolerability than the conventional ones. Several new AEDs can allow young women with epilepsy, particularly those with idiopathic generalized epilepsy, to avoid valproic acid treatment. Furthermore, the new AEDs may provide a modest but positive effect in seizure control, particularly as an add-on treatment. The greater variety of AEDs allows better patient tailoring according to patient's characteristics and contributes to improvement in quality of life.

New Antiepileptic Drugs in Childhood Epilepsy

Many new antiepileptic drugs (AEDs) have been developed in the last two decades, contributing to the optimal treatment for childhood epilepsy. The goal of the treatment is to achieve seizure-free without any side effects, that deteriorates the quality of life by causing negative consequences. The new AEDs have not shown better efficacy, but generally seem to be better tolerated, having fewer systemic reactions and better pharmacokinetics than the established AEDs. The new AEDs have a broad spectrum of activities, which offer new opportunities to patients who have not shown any favorable responses to the established ones. There are more choices when trying to select AEDs for epileptic seizures and syndromes. Majority of the new AEDs have more than one action mechanism. AEDs acting selectively through the GABAergic system are tiagabine and vigabatrin; acting by inhibition of voltagedependent Na+ and Ca2+ channels are lamotirigine, oxcabarbazepine and topiramate; and acting by inhibition of glutamate-mediated excitation are felbamate, topiramate. The pharmacokinetic parameters of the new AEDs compared to the established AEDs, new AEDs have improved in terms of longer half-lives, permitting less frequent daily dosing, reduced potential for drug interactions. Considerations in selecting an AEDs are not only dependent on seizure types or syndromes, side effect profile, action mechanism, drug interaction, pharmacokinetic profile, facility of drug initiation, but also on age and sex of patients. Patients with worsened seizurefrequency or development of new types of seizure after the introduction of AEDs, should be questioned on the previously diagnosed seizure types or syndromes.