Effects of long-term antiepileptic polytherapy on bone biochemical markers in ambulatory children and adolescents and possible benefits of vitamin D supplementation: a prospective interventional study.

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 ±â€¯4.6 and 11.4 ±â€¯4.4 yrs. RESULTS: The basal mean 25(OH)D levels in the patients did not differ from controls (23.9 ±â€¯11.5 vs 27.4 ±â€¯13.3 ng/ml), but increased significantly after the vitamin D intake (31.1 ±â€¯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 ±â€¯0.63 vs 1.22 ±â€¯0.58 ng/ml, p < 0.02), but not tALP. Osteoprotegerin was higher in the patients (5.7 ±â€¯7.7 pmol/L vs 2.6 ±â€¯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 ±â€¯0.57 ng/ml), and those of OPG decreased to levels that did not differ from controls (4.9 ±â€¯5.1 pmol/L). The ratio of OPG/sRANKL was higher in patients than controls before treatment (0.030 ±â€¯0.045 vs 0.009 ±â€¯0.005, p < 0.03), but decreased (0.026 ±â€¯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.

Vitamin D supplementation and bone markers in ambulatory children on long-term valproic acid therapy. A prospective interventional study.

PURPOSE: Our aim was to investigate any adverse effects of long-term valproic acid (VPA) 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 single center, the prospective interventional study levels of 25-hydroxyvitamin D (25OHD) and the bone turnover indices of Crosslaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were assessed before and after one year of vitamin D intake (400 IU/d) and were compared with those of clinically healthy controls. Fifty-four ambulatory children with mean (±standard deviation [SD]) age 9.0 ±â€¯4.5 yrs on VPA (200-1200 mg/d) long-term monotherapy (mean: 3.2 ±â€¯2.6 yrs) were studied, before and after a year's vitamin D intake (400 IU/d). RESULTS: Nearly half of the cases were vitamin D insufficient/deficient with mean levels 23.1 ±â€¯12.8 vs 31.8 ±â€¯16.2 ng/mL of controls (p = 0.004) and after the year of vitamin D intake increased to 43.2 ±â€¯21.7 ng/mL (p < 0.0001). In parallel, serum CTX and tALP had a decreasing trend approaching control levels but OPG and sRANKL did not change and were not different from controls. However, after vitamin D intake, a positive correlation was seen between 25OHD and OPG but not before. CONCLUSIONS: The findings imply a higher bone turnover in the young patients on long-term VPA therapy that decreased after vitamin D intake.