Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.
Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.
复制标题
长期服用抗癫痫药唑尼沙胺对生长大鼠骨矿物质密度的影响及其用阿法骨化醇的预防作用。
DOI：
10.1254/jphs.91.313
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发表时间：
2003
影响因子：
3.5
通讯作者：
H. Mayanagi
中科院分区：
文献类型：
--
作者：
A. Takahashi;K. Onodera;J. Kamei;S. Sakurada;H. Shinoda;S. Miyazaki;Takashi Saito;H. Mayanagi
我们研究了长期服用抗癫痫药唑尼沙胺对生长大鼠骨代谢的影响。唑尼沙胺80mg /kg /天，s.c.连续5周显著降低胫骨干骺端和骨干的骨密度（BMD）。胫骨干骺端和胫骨干骺端骨密度下降的百分比分别为9.2%和5.0%。各组大鼠的生长无显著差异。zonisamide治疗剂量为80 mg/kg，可增加血清吡啶啉水平（骨吸收的标志），但不影响血清完整骨钙素水平（骨形成的标志）。阿法骨化醇是一种活性维生素D(3)代谢物，每日0.1微克/公斤的剂量与唑尼沙胺联合使用，可防止骨密度下降，并显示血清吡啶啉水平升高。这些结果表明佐尼沙胺可能通过加速骨吸收而不是抑制骨形成而导致骨质流失。此外，佐尼沙胺与阿法骨化醇联用可预防佐尼沙胺所致的骨质流失。
We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg/kg per day, s.c. for 5 weeks significantly decreased bone mineral density (BMD) at the tibial metaphysis and the diaphysis. The percent rate of decrease in BMD at the tibial metaphysis and the tibial diaphysis was 9.2% and 5.0%, respectively. There was no significant difference between these groups in the growth of the rats. Treatment with zonisamide at a dose of 80 mg/kg increased serum pyridinoline level, a marker of bone resorption, while it does not affect the serum intact osteocalcin level, a marker of bone formation. Combined administration of alfacalcidol, an active vitamin D(3) metabolite, at a dose of 0.1 microg/kg per day with zonisamide prevented a decrease in BMD and showed an increase of serum pyridinoline levels. These results suggest that zonisamide may cause bone loss by accelerating bone resorption rather than inhibiting bone formation. Moreover, the bone loss induced by zonisamide could be prevented by combining zonisamide with alfacalcidol.