The effect of phenytoin monotherapy on serum 25-hydroxyvitamin D and bone health markers -A prospective study

Phenytoin monotherapy in patients with epilepsy affects calcium metabolism and bone turnover markers leading to hypovitaminosis D, hypocalcemia, reduced bone mineral density and its imminent consequences. This study was planned to assess how early these changes may arise and to find out their correlation with phenytoin levels. In this prospective study, bone mineral density (BMD), 25-hydroxy vitamin D, urinary hydroxyproline were estimated at baseline, 2 and 6 months after phenytoin monotherapy and serum phenytoin levels were measured at 2 and 6 months of therapy. At 6 months, BMD showed a decrease (T-score -1.22±1.049 to -1.412±1.055, p value <0.001) while vitamin D levels started decreasing as early as 2 months after therapy and decreased further after 6 months (32.93±6.38 ng/mL to 31.46±5.99 ng/mL at 2 months and then to 29.96±5.94 ng/mL, p value <0.05 and <0.001 respectively). Urine hydroxyproline levels were 16.65±2.22 mg/day at diagnosis and increased to 16.97±2.25 mg/day after 2 months and to 18.544±2.83 mg/day after 6 months (pvalue <0.001 at 6 months). Mean serum phenytoin levels at 2 months were 15.74 ± 9.49 mg/L and while at 6 months these were observed to be 15.92 ± 5.54 mg/L. Urine hydroxyproline levels correlated positively with phenytoin levels (r-0.447, p value <0.05). Bone health derangement starts at around 2 months while at six months of phenytoin therapy, there is significant decline in bone health as indicated by status of markers like BMD and urine hydroxyproline.