Boluk Ayhan, Guzelipek Mehmet, Savli Haluk, Temel Ismail, Ozişik Handan Işin, Kaygusuz Akif
Department of Neurology, Turgut Ozal Medical Center, University of Inonu, Malatya, Turkey.
Pharmacol Res. 2004 Jul;50(1):93-7. doi: 10.1016/j.phrs.2003.11.011.
The effect of long-term valproate (VPA) treatment on bone mineral density (BMD) in adult epileptic patients is not clearly known, although several studies have been done in children. In adult epileptic patients (n = 50; 24 men, 26 women) treated with VPA, the bone mineral density at lumbar level (L1-L4) and neck, trochanter, and intertrochanter regions of left femur was studied by dual energy X-ray absorptiometry (DXA) at the beginning of the study and after 6 months, with the specific aim to evaluate the effect of long-term valproate monoteraphy on bone mineral density. Routine biochemical parameters were also evaluated. Sixty healthy control subjects were evaluated. Control subjects were similar to patient group with respect to age, race (all White), geographic area, and socioeconomic status. Lumbar and femural BMD values were significantly lower in patient group than control group (0.814 +/- 0.157 g/cm(2) versus 0.894 +/- 0.102 g/cm(2), P = 0.003) and (0.824 +/- 0.144 g/cm(2) versus 0.906 +/- 0.104 g/cm(2), P = 0.001), respectively. Osteopenia were detected in 13 of 60 control subjects (22%) and the others had no osteoporosis. In epileptic group, osteoporosis and osteopenia were detected in 8 subjects (16%), and in 26 subjects (52%), respectively. In epileptic group 16 subjects were normal (32%) at the lumbar regions, and 7 had osteoporosis (14%), 28 had osteopenia (56%), and 15 were normal (30%) at the femoral region. In the second measurements of the patients on valproate treatment, after 6 months, all of the DXA BMD values had worsened compared with the first measurements (P = 0.001 for lumbar BMD values and P = 0.004 for femural BMD values). In the patient group, a significant inverse correlation was observed between duration of valproate therapy and all DXA BMD values in the first and second measurements. Parathyroid hormone, alkaline phosphatase, and phosphor levels of patients were significantly higher than those of control group (52 +/- 11 pg/ml versus 46 +/- 13 pg/ml, P = 0.013), (113 +/- 32 U/l versus 95 +/- 36 U/l, P = 0.006), and (4.50 +/- 0.5 mg/dl versus 4.0 +/- 0.7 mg/dl, P = 0.0001), respectively. However, all of the parameters were within the normal reference ranges. It has been concluded that long-term (more than one year) valproate treatment induces a decrease in bone mineral density in epileptic adults. However, the multivariate analysis did show no association between BMD changes and parathyroid hormone, alkaline phosphatase or phosphorus levels.
尽管已针对儿童开展了多项研究，但长期丙戊酸盐（VPA）治疗对成年癫痫患者骨密度（BMD）的影响尚不清楚。在接受VPA治疗的成年癫痫患者（n = 50；24名男性，26名女性）中，于研究开始时及6个月后，采用双能X线吸收法（DXA）对腰椎水平（L1 - L4）以及左股骨颈、大转子和转子间区域的骨密度进行了研究，其具体目的是评估长期丙戊酸盐单药治疗对骨密度的影响。还评估了常规生化参数。对60名健康对照者进行了评估。对照者在年龄、种族（均为白人）、地理区域和社会经济地位方面与患者组相似。患者组的腰椎和股骨骨密度值显著低于对照组（分别为0.814±0.157 g/cm² 与0.894±0.102 g/cm²，P = 0.003）以及（0.824±0.144 g/cm² 与0.906±0.104 g/cm²，P = 0.001）。60名对照者中有13名（22%）检测出骨质减少，其他对照者无骨质疏松。在癫痫组中，分别有8名受试者（16%）检测出骨质疏松，26名受试者（52%）检测出骨质减少。在癫痫组中，16名受试者腰椎区域正常（32%），7名有骨质疏松（14%），28名有骨质减少（56%），15名股骨区域正常（30%）。在接受丙戊酸盐治疗的患者进行第二次测量时，即6个月后，所有DXA骨密度值与首次测量相比均有所恶化（腰椎骨密度值P = 0.001，股骨骨密度值P = 0.004）。在患者组中，首次和第二次测量时均观察到丙戊酸盐治疗持续时间与所有DXA骨密度值之间存在显著负相关。患者的甲状旁腺激素、碱性磷酸酶和磷水平显著高于对照组（分别为52±11 pg/ml 与46±13 pg/ml，P = 0.013）、（113±32 U/l 与95±36 U/l，P = 0.006）以及（4.50±0.5 mg/dl 与4.0±0.7 mg/dl，P = 0.0001）。然而，所有参数均在正常参考范围内。得出的结论是，长期（超过一年）丙戊酸盐治疗会导致成年癫痫患者骨密度降低。然而，多变量分析并未显示骨密度变化与甲状旁腺激素、碱性磷酸酶或磷水平之间存在关联。
