Abstracts

Rationale: Patients taking anti-epileptic drugs (AEDs) have increased fracture risk. Data is limited regarding effects of age of commencement of AEDs, particularly with respect to AED-use at younger ages and the achievement of peak bone mass. We investigated: (1) bone health in gender-matched, AED-discordant twin/sibling pairs; (2) associations of age of onset of epilepsy with bone mineral density (BMD), stratifying pairs where AED-user commenced AED before or after 18 years, an age by when the majority of bone mass is attained. Methods: Fifty AED (and epilepsy)-discordant pairs were studied. DXA scans were acquired (Hologic 4500A/1000W), measuring BMD at lumbar spine (LS), total hip (TH), femoral neck (FN), total forearm (FA) and total body bone mineral content (TBBMC). Data was adjusted for age, height, weight. Mean within-pair differences (MWPD) (AED-user - non-user) and percentage MWPD [(AED-user - non-user)/non-user]*100 were calculated using paired t-tests. Independent t-tests compared within-pair differences of pairs where the AED-user commenced AED under versus over 18 years. Results: 40 female, 10 male pairs (17 monozygous, 15 dizygous twins and 18 sib pairs), mean (SD) age 44.5 (15.8) years were studied. For the 27 pairs where the AED-user commenced AED before 18 years of age (with current mean age 37.8 (15.0) years), there was a significant MWPD in height (-0.02m, p=0.021), and BMD at LS (-6.51%, p=0.011), TH (-7.06%, p=0.009), and FN (-10.53%, p=0.0002). There were no significant MWPDs in age, height, BMI, calcium intake, total fat mass or total lean mass. For 23 pairs where the AED-user commenced AED ≥18 years of age (with current mean age 52.8 (12.7) years), there was a significant MWPD in calcium intake (+278mg, p=0.021). There were significant differences in the MWPDs between the groups at the TH, FN and in TBBMC, where AED-users who commenced therapy aged less than 18 years had reduced BMD at TH, FN and TBBMC compared to pairs where the AED-user commenced after 18 years of age. There was no significant difference in AED duration [Mean (SD) AED use: <18y: 20.5 (14.6) years; ≥18y: 15.2 (12.1) years, p=0.170.] Conclusions: Commencement of AED therapy at a younger age is associated with shorter stature, and reduced BMD at clinically-relevant sites for fracture risk. Whether this is primarily attributable to an AED-associated reduction in peak bone mass or is influenced by duration of the epileptic disorder or other factors requires further, longitudinal studies, commencing in the paediatric age group.