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 ± 4.5 yrs on VPA (200-1200 mg/d) long-term monotherapy (mean: 3.2 ± 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 ± 12.8 vs 31.8 ± 16.2 ng/mL of controls (p = 0.004) and after the year of vitamin D intake increased to 43.2 ± 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.