Abstracts

Rationale: Patients taking anti-epileptic drugs (AEDs) are reported to have an increased risk of low bone mineral density (BMD) and fractures; however the causes and risk factors for these reported associations are uncertain. We aimed to investigate effects of AED usage on bone mineral density by utilizing a treatment-discordant twin and sibling matched pair design, comparing AED-user to the matched twin/sibling with no history of epilepsy or AED use. To examine clinically relevant subgroups including: (A) current use, (B) polytherapy and (C) epilepsy as the indication for treatment.Methods: 56 pairs discordant for AED usage were studied: (46 current, 10 past AED users; 47 female, 9 male; 21 MZ, 21 DZ twins, 14 sib pairs matched within 3 years of age) with mean (SD) age 45.6 (15.3). BMD was measured (Hologic 4500A or 1000W) at lumbar spine (LS), total hip (TH), femoral neck (FN), total forearm (FA) and total body bone mineral content (TB BMC); data adjusted for age, height and weight. Lifetime duration (LDT) and number (LNM) of AEDs were calculated. Results of paired t-tests were expressed as the within-pair percentage difference, relative to the non-user.Results: Overall group: No significant within-pair difference in age, height, weight, total fat or total lean mass. Significant within-pair differences seen in BMD (AED-user vs. non-user) in the whole group at TH -4.2% (p=0.02), LS -4.0% (p=0.03) and in the subgroups: (A) Current: TH -5.4% (p=0.01), FN -4.3% (p=0.045), LS – 4.8% (p=0.03); (B) Polytherapy: FA -3.4% (p=0.049), TH -8.9%(p=0.04), FN -9.7% (p=0.00) [n=14, mean(SD) LMN 3.27(1.94), mean LDT 20.8y(10.3)]; (C) Epilepsy: TH -5.35% (p=0.01), FN -4.29%(p=0.046), LS -4.8% (p=0.03) (n=41, LDT(SD) 20.8(13.7)yrs.Conclusions: Patients taking AEDs for epilepsy and particularly taking polytherapy have reduced BMD when compared to their gender-matched twin/sibling. Whether these results reflect severity of epilepsy or duration and number of AEDs used requires further investigation.