Abstracts

There is considerable evidence that older antiepileptic drugs (AEDs) such as phenobarbital and phenytoin adversely affect bone health. However, data regarding newer AEDs such as levetiracetam is lacking. We, therefore, studied the effects of levetirecetam on bone density, vitamin D and osteocalcin levels., After IRB approval patients on levetiracetam monotherapy for greater than six months were enrolled. Sixteen patients (eight men and eight women) agreed to participate in the study. A detailed questionnaire was used to review medical history. Osteocalcin were measured by chemiluminescent immunoassay and and 1, 25 hydroxy vitamin D levels by a radioimmunoassay. Dual energy X-ray absorptiometry (DEXA) was performed using Hologic System., The mean age of these patients was 37 years (range 20-66 years). Mean duration of therapy with levetirecetam as monotherapy was 27 months (range 6-60 months). The mean serum 1, 25 hydroxy-vitamin D level was 42.5 pg/mL (range 17-100 pg/mL). None of these patients had an abnormally low vitamin D level noted. Mean serum osteocalcin level was 6.4 ng/mL (range 1.8-14.1). Four of the sixteen (25%) of the patients had elevated osteocalcin levels.Two of these had mildly abnormal bone density measurements when compared to normal young adults matched for gender (t score). All four had previous exposure to other AEDs including phenytoin, sodium valproate, carbamazepine and phenobarbital.
All sixteen patients underwent DEXA scan. None of the patients had evidence of osteopenia or osteoporosis when compared to age and sex matched controls (z score [gt] -2.0). Borderline abnormal t scores were noted in two patients at lumbar spine level who also had elevated osteocalcin levels. However, these patients had been treated with multiple AEDs prior to being on keppra monotherapy.
A significant positive linear correlation was noted between serum 1, 25 hydroxy vitamin D levels and bone mineral density. (r = 0.54, p [lt] 0.05)., Levetiracetam does not appear to be associated with a significant decrease in vitamin D levels or bone mineral density. Elevation of osteocalcin levels, implying increased bone turnover was noted in four patients but this finding alone is of unclear clinical significance and requires further study. Slight reduction in BMD in two patients can potentially be explained by previous, prolonged exposure to other AEDs known to cause bone loss. This confounding variable needs to be considered in all cross-sectional studies such as ours in assessing bone mineral density with newer AEDs. Controlled prospective studies in patients with new onset seizures may be a better method of studying effects of newer AEDs on bone mineral density., (Supported by UCB Pharmaceuticals.)