osteoprotegerin and Epilepsy

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.. 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).. 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.. The findings imply a higher bone turnover in the young patients on long-term VPA therapy that decreased after vitamin D intake.

Topics: Adolescent; Alkaline Phosphatase; Anticonvulsants; Biomarkers; Bone and Bones; Bone Remodeling; Child; Dietary Supplements; Epilepsy; Female; Humans; Hydroxycholecalciferols; Male; NF-kappa B; Osteoprotegerin; Prospective Studies; Valproic Acid; Vitamin D; Vitamin D Deficiency; Vitamins

Epilepsy is a major public health problem affecting nearly 50 million people world wide. Treatment with anti-epileptic drugs (AEDs) is generally chronic if not life long and may be associated with significant metabolic effects including decreased bone mass and increased fractures. The aim of this work was to investigate the protective role of fish liver oil and propolis against the effect of the drug valproate that is widely used for treatment of epilepsy. Group of 40 rats was divided into four groups each contain 10 rats. The first group (group I) is healthy normal rats, as control. Epilepsy was conducted in the rest of the rats. The epileptic rats were divided into three subgroups: group II was epileptic group, supplemented orally with valproate. The third group was epileptic group which supplemented orally with valproate in concomitant with fish liver oil, the last group; group IV was epileptic group which supplemented orally with valproate in concomitant with propolis. In the present study oral administration of valproate to the epileptic rats by a dose of 400mg/kg/daily for six months (group II) resulted in a significant increase of bone alkaline phosphatase, osteocalcin and N-telepeptide of type 1 collagen (NTX) relative to the control group. There were increase of receptor activator of NF kappa B ligand (RANKL), tumor necrosis factor - alpha (TNF-alpha) and decrease of osteoprotegrin (OPG) compared to normal control. Administration of fish liver oil orally in a dose of 0.4mg/kg daily in concomitant with valproate 400mg/kg daily for six months (group III), result in reduction of N-telepeptide of type 1 collagen (NTX) in comparison to group II and with no significant increase than the control (group I). There were high significant increase of bone alkaline phosphatase and osteocalcin compared to control group I. There was high significant increase of bone alkaline phosphatase than group II and increase in osteocalcin, and decrease in N-telepeptide of type 1 collagen (NTX) compared to group II. A significant increase in osteoprotegrin (OPG) in comparison to group II and to control (group I) with a decrease in RANKL compared to group II and with no significant increase than normal control (group I). The TNF-alpha showed a significant decrease compared to group II with no significant increase than normal control. Administration of propolis orally in a dose of 50mg/kg daily in combination with valproate 400mg/kg/daily for six months (group IV) cause incr

Topics: Alkaline Phosphatase; Animals; Anticonvulsants; Atropine; Biomarkers; Bone Resorption; Disease Models, Animal; Epilepsy; Fish Oils; Male; Osteocalcin; Osteogenesis; Osteoporosis; Osteoprotegerin; Pilocarpine; Propolis; RANK Ligand; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha; Valproic Acid