A 12-month longitudinal study of calcium metabolism and bone turnover during valproate monotherapy

Background and purpose: Treatment with valproate (VPA) can cause changes in bone mineral metabolism, but the real influences and the underlying pathologic mechanisms are still unclear and under discussion. The aim of this study was to examine the changes on calcium metabolism and bone turnover in post-pubertal male patients with newly diagnosed idiopathic generalized epilepsy (IGE) before (baseline evaluation) and 12 months after VPA monotherapy (second evaluation). Methods: Participants included 20 post-pubertal males with IGE, aged 16.5-22.1 years. Also 20 post-pubertal sex- and age-matched healthy controls were evaluated. Physical activity, calcium and vitamin D intake were determined. Laboratory samples were obtained to measure biochemical parameters of bone metabolism and bone turnover: serum calcium, phosphate, magnesium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact parathyroid hormone, total alkaline phosphatase, bone alkaline phosphatase (bone-ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP). Results: At baseline evaluation, there were no significant differences between controls and patients parameters. At second evaluation, patients showed both markers of bone formation and resorption significantly higher than baseline values (bone-ALP: 51.2 +/- 9.9 vs. 57.3 +/- 9.3 U/l, P < 0.01; OC: 8.1 +/- 1.1 vs. 10.4 +/- 1.5 mu g/l, P < 0.01; PICP: 138.7 +/- 16.4 vs. 152.6 +/- 17.1 mu g/l, P < 0.01; ICTP: 3.8 +/- 0.8 vs. 5.9 +/- 0.6 mu g/l, P < 0.01). Conclusions: Valproate monotherapy in epileptic post-pubertal males causes a significant increase of bone turnover.