PURPOSE Our aim was to investigate any adverse effects of long-term polytherapy (VPA and add-on-therapy) on bone biochemical markers in ambulatory children and adolescents with epilepsy and the possible benefits of vitamin D supplementation on the same markers. METHODS In this prospective interventional study, the levels of 25(OH)D and the bone turnover markers of CrossLaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were determined in forty-two ambulatory children with epilepsy on polytherapy (valproic acid + one or more other from levetiracetam, topiramate, lamotrigine, or rufinamide). The same markers were assessed after a year's supplementation of vitamin D (400 IU/d) and were compared with those of clinically healthy controls. The respective mean (±SD) ages were 11.9 ± 4.6 and 11.4 ± 4.4 yrs. RESULTS The basal mean 25(OH)D levels in the patients did not differ from controls (23.9 ± 11.5 vs 27.4 ± 13.3 ng/ml), but increased significantly after the vitamin D intake (31.1 ± 13.3 ng/ml, p < 0.01). In parallel, basal serum CTX levels were found to be significantly lower in the patients than controls (0.89 ± 0.63 vs 1.22 ± 0.58 ng/ml, p < 0.02), but not tALP. Osteoprotegerin was higher in the patients (5.7 ± 7.7 pmol/L vs 2.6 ± 1.0 pmol/L, p < 0.03), while sRANKL did not differ. After vitamin D, the CTX levels increased to comparable levels in controls (0.99 ± 0.57 ng/ml), and those of OPG decreased to levels that did not differ from controls (4.9 ± 5.1 pmol/L). The ratio of OPG/sRANKL was higher in patients than controls before treatment (0.030 ± 0.045 vs 0.009 ± 0.005, p < 0.03), but decreased (0.026 ± 0.038) to comparable values in controls later. CONCLUSIONS These findings imply a lower bone turnover in the young patients on long-term polytherapy (VPA and add-on-therapy), but after one year's vitamin D intake, bone biochemical markers improved.

中文翻译：

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长期抗癫痫综合疗法对非卧床儿童和青少年骨生化指标的影响以及补充维生素 D 的可能益处：一项前瞻性干预研究

目的 我们的目的是研究长期综合疗法（VPA 和附加疗法）对非卧床儿童和癫痫青少年骨生化指标的任何不利影响，以及补充维生素 D 对相同指标的可能益处。方法 在这项前瞻性干预研究中，25(OH)D 的水平和 CrossLaps (CTX)、总碱性磷酸酶 (tALP)、骨保护素 (OPG) 和核因子 kB 受体激活剂 (RANK) 配体的骨转换标志物的水平(sRANKL) 在 42 名接受多药治疗（丙戊酸 + 左乙拉西坦、托吡酯、拉莫三嗪或卢非酰胺中的一种或多种其他药物）的非卧床儿童中测定。在补充维生素 D (400 IU/d) 一年后评估了相同的标志物，并与临床健康对照的标志物进行了比较。各自的平均 (±SD) 年龄分别为 11.9 ± 4.6 和 11.4 ± 4.4 岁。结果 患者的基础平均 25(OH)D 水平与对照组没有差异（23.9 ± 11.5 vs 27.4 ± 13.3 ng/ml），但在摄入维生素 D 后显着增加（31.1 ± 13.3 ng/ml，p < 0.01 ）。同时，发现患者的基础血清 CTX 水平显着低于对照组（0.89 ± 0.63 对 1.22 ± 0.58 ng/ml，p < 0.02），但 tALP 没有。患者的骨保护素较高（5.7 ± 7.7 pmol/L vs 2.6 ± 1.0 pmol/L，p < 0.03），而 sRANKL 没有差异。服用维生素 D 后，CTX 水平增加至对照组的可比水平 (0.99 ± 0.57 ng/ml)，而 OPG 的水平下降至与对照组无差异的水平 (4.9 ± 5.1 pmol/L)。治疗前患者的 OPG/sRANKL 比值高于对照组（0.030 ± 0.045 vs 0.009 ± 0. 005, p < 0.03)，但后来在对照中降低 (0.026 ± 0.038) 至可比值。结论 这些发现意味着接受长期综合疗法（VPA 和附加疗法）的年轻患者的骨转换较低，但在摄入维生素 D 一年后，骨生化指标有所改善。