Vahar-Matiar M, Fröscher W
Universitäts-Nervenklinik Bonn.
Fortschr Neurol Psychiatr. 1988 Jul;56(7):216-30. doi: 10.1055/s-2007-1001786.
Since Schmid (115) and Kruse (74) reported on osteopathies occurring after antiepileptic treatment in children, there have been numerous publications concerning the influence of antiepileptics on mineral metabolism in the bones. The investigators' results range from slight anomalies of the plasma levels of calcium, phosphate, alkaline phosphatase, parathormone and 25-hydroxycholecalciferol to severe bone alterations. In the majority of cases, the severe pictures occurred in retarded, neurologically abnormal, institutionalised children who were treated with a high-dose combination of several antiepileptics for epilepsy which was difficult to treat. The first case reports from adults were published by Dent et al. (26). These patients had also been treated since their early youth with an antiepileptic combination. They displayed fractures and suffered from bone pain and muscular weakness. The good response of the rachitic bone alterations to vitamin D treatment both in children and in adults indicated vitamin D deficiency. These reports prompted systematic investigations on the influence of antiepileptics on bone metabolism in numerous hospitals and outpatient departments. According to the available literature, it can be stated that antiepileptic therapy can lead to shifts in calcium and phosphate metabolism and to a raised activity of serum alkaline phosphatase. In studies comprising control groups, the patient treated with anticonvulsants more frequently displayed variations of clinical laboratory parameters. The frequent observation of vitamin D hypovitaminosis led to the assumption that alterations in vitamin D metabolism by enzyme induction are the cause of the disorders in calcium and vitamin D metabolism. This hypothesis was frequently contradicted in recent years after hypocalcaemia and alterations in the mineral content of the bone after antiepileptic therapy had been reported irrespective of the vitamin D level. Besides a restricted intestinal calcium absorption, an influence of antiepileptics on the hormones regulating calcium and phosphate metabolism was found. Thus, a multifactorial genesis of the disorders in bone mineral balance must be assumed. The fact that the vast majority of outpatients with long-term anticonvulsant therapy do not display any disorders of bone metabolism indicate that there are individually different compensation capabilities (possibly of genetic origin). According to the literature, the probability that adults will develop osteomalacia under antiepileptic therapy is associated with the joint presence of various risk factors.(ABSTRACT TRUNCATED AT 400 WORDS)
自从施密德(115)和克鲁泽(74)报道了儿童抗癫痫治疗后出现的骨病以来,已经有许多关于抗癫痫药物对骨骼矿物质代谢影响的出版物。研究人员的结果从血浆钙、磷、碱性磷酸酶、甲状旁腺激素和25-羟胆钙化醇水平的轻微异常到严重的骨骼改变不等。在大多数情况下,严重的情况发生在发育迟缓、神经异常、住院治疗的儿童身上,这些儿童因难以治疗的癫痫而接受几种抗癫痫药物的高剂量联合治疗。成人的首例病例报告由登特等人(26)发表。这些患者从幼年起也接受了抗癫痫药物联合治疗。他们出现了骨折,并患有骨痛和肌肉无力。佝偻病性骨骼改变在儿童和成人中对维生素D治疗的良好反应表明维生素D缺乏。这些报告促使众多医院和门诊部对抗癫痫药物对骨代谢的影响进行系统研究。根据现有文献,可以说抗癫痫治疗可导致钙和磷代谢的改变以及血清碱性磷酸酶活性的升高。在有对照组的研究中,接受抗惊厥药物治疗的患者更频繁地出现临床实验室参数的变化。维生素D缺乏症的频繁观察导致人们认为酶诱导引起的维生素D代谢改变是钙和维生素D代谢紊乱的原因。近年来,在报道了抗癫痫治疗后低钙血症和骨矿物质含量改变而与维生素D水平无关之后,这一假设经常遭到反驳。除了肠道钙吸收受限外,还发现抗癫痫药物对调节钙和磷代谢的激素有影响。因此,必须假定骨矿物质平衡紊乱是多因素成因。绝大多数长期接受抗惊厥治疗的门诊患者没有表现出任何骨代谢紊乱这一事实表明存在个体差异的代偿能力(可能源于遗传)。根据文献,成人在抗癫痫治疗下发生骨软化症的概率与多种危险因素的共同存在有关。(摘要截取自400字)