Abstracts

Rationale: Persons with epilepsy have increased risk of fracture. Seizures and ntiepileptic drugs (AEDs) may increase the risk. Enzyme inducing AEDs (EIAEDs) are associated with bone abnormalities. We aimed to evaluate whether persons with epilepsy on EIAEDs have reduced bone parameters relative to normative values; differ from those not on EIAEDs; and if cumulative exposure to EIAEDs is associated with reduced areal bone mineral density (aBMD) and bone quality. Methods: We studied 103 persons with epilepsy on AEDs: 34 men (58 7), 48 premenopausal women (PreM) (37 7) and 21 postmenopausal women (PostM) (61 5). AED exposure was ascertained by questionnaire and chart review. Inducer status was defined by current EIAED use. Cumulative exposure was calculated as years of current EIAED use plus years of prior EIAED use divided by years since EIAEDs were last taken. Excluded were subjects with diseases or taking medications affecting the skeleton. aBMD by DXA (Hologic QDR 4500) was measured at spine (LS), total hip (TH), femoral neck (FN), and radius (R). Volumetric BMD (vBMD) and trabecular (Tb) and cortical (Ct)microarchitecture were measured at the non-dominant distal R and tibia (T) by HR-pQCT (XtremeCT; SCANCO Medical AG; voxel size ~82um). Sex-specific Z-scores were compared to reference normative values from Hologic Corp for DXA and Boutroy and Chaitou et al. (JBMR, 2010) for HR-pQCT. Z-scores were compared to reference norms and by inducer status by T-test, and with regression analysis to determine the impact of cumulative EIAED exposure. Results: When compared to norms, PreM on EIAEDs had higher aBMD at LS and R. PreM demonstrated higher Tb number and lower Tb thickness at the R and T and lower T Tb separation. PostM on EIAEDs had lower Ct vBMD and trend to higher Tb number and lower Tb separation and heterogeneity at the T. Men showed lower Tb thickness at both sites and a trend toward higher T total area. When compared by inducer status, PreM on EIAEDs had higher LS, TH and FN aBMD. Men on EIAEDs had higher total area at the R. When analyzed by cumulative exposure to EIAEDs (reported as change in Z-score per additional year of EIAED exposure), PreM had lower Tb vBMD (-0.053), Tb number (-0.073), and higher Tb separation and heterogeneity (0.085 and 0.108) at the R. In PostM Tb vBMD (0.042) and number (0.047) trended to higher at the T. Men had lower R aBMD (-0.032), Tb thickness at both sites (-0.034 and -0.038) and higher total vBMD (0.030). Conclusions: Prior studies would predict poorer bone parameters in subjects taking EIAEDs. Subjects in this study treated with EIAEDs did not have lower aBMD and only few differences in microarchitecture when compared to normative controls and those not on EIAEDs. In contrast, when EIAED exposure is viewed as a cumulative insult, EIAED exposure was associated with reduced Tb density and number as well increased TB separation and heterogeneity. The complex AED history of persons with epilepsy may require an index of cumulative exposure to have a better overview of the long term effects of EIAEDs on the skeleton. Supported by NIAMS 1K23053113