Simko Julius, Fekete Sona, Gradosova Iveta, Malakova Jana, Zivna Helena, Valis Martin, Palicka Vladimir, Zivny Pavel
Department of Neurology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
J Neurol Sci. 2014 May 15;340(1-2):80-5. doi: 10.1016/j.jns.2014.02.032. Epub 2014 Mar 3.
There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.
关于新型抗癫痫药物对骨骼的影响，目前仅有有限的数据。本研究的目的是确定托吡酯（TPM）和拉莫三嗪（LTG）单药治疗对去势（ORX）大鼠模型的骨矿物质密度（BMD）、矿物质含量（BMC）、骨标志物、身体成分和骨机械强度的影响。将24只去势的Wistar大鼠分为对照组和试验组，每组8只。对照大鼠给予标准实验室饮食（SLD），而试验组大鼠则用富含LTG或TPM的SLD喂养12周。采用双能X线吸收法测量骨矿物质密度。在骨匀浆中测定骨代谢标志物的浓度。此外，对两侧股骨进行测量并用于生物力学测试。与对照组相比，两个试验组的体重、脂肪量、全身和股骨的BMD、BMC均显著降低，骨机械强度也降低。所有这些变化在暴露于LTG的大鼠中更为明显。总之，LTG和TPM均显著降低BMD和体重，并损害骨机械强度。一个问题是这种效应在多大程度上依赖于剂量。有必要进一步研究以确定LTG和TPM是否仅在去势大鼠模型中对BMD有临床显著影响，或者这种效应是否也适用于性腺完整动物模型以及相应的人体模型。
