Abstracts

Population based studies of fractures consistently identify anticonvulsants as a risk factor for osteoporotic related fractures. Phenytoin and phenobarbital have been shown to accelerate bone loss and carbamazepine has also been implicated. The mechanism for this adverse outcome is believed to be due to cytochrome P-450 enzyme induction that causes an increased clearance of vitamin D. Reduced vitamin D levels results in activation of parathyroid hormone and subsequent mobilization of calcium from bone and over time may lead to osteopenia and increased fracture risk. Supplementation with vitamin D has been recommended to limit demineralization. Doses of 400-2000 internation units (IU) daily are recommended for patients on anticonvulsant therapy. However there is no data that describes changes in vitamin D levels with supplements of vitamin D in the presence of enzyme inducers. From January 2003 to March of 2004 levels of 25-hydroxy vitamin D were assayed by the Nichols chemiluminescent immunoassay in a patient on escalating doses of ergocalciferol. Initial supplementation at a dose of vitamin D of 400 IU daily found the 25-hydroxy vitamin D level at 16ng/ml. At 50,000 IU biweekly the Vitamin D level was 34ng/ml. This institutionalized 41 year-old female with a life-long history of epilepsy and exposure to multiple anticonvulsants including phenobarbital, phenytoin and divalproex, had suffered multiple fractures. She was found to be osteopenic, likely related to long-term exposure to vitamin D-depleting anticonvulsants. Normalization of vitamin D may limit her ongoing risk. Serial increases in vitamin D were necessary to normalize her level. Doses of 50,000 IU of vitamin D in healthy individuals would appear to be excessive, but may be required in the presence of enzyme inducers.