Osteoporosis Associated With Epilepsy, Independent of ASM Use, Study Finds

Epilepsy was independently associated with clinically meaningful increases in the risk of osteoporosis, with enzyme-inducing antiseizure medications (eiASMs) and non-eiASMs associated with significant increases in the risk of epilepsy, according to a new study.

This study, published in JAMA Neurology, highlights the importance of routine screening and prophylaxis in all patients with epilepsy.

“Incident adult-onset epilepsy, independent of ASM use, appears to accelerate time to osteoporosis by approximately 41% compared with the general population,” wrote the researchers of the study. “The underlying mechanisms linking epilepsy and osteoporosis have been insufficiently studied compared with the role of ASMs.”

The open cohort included 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Patient data were collected from patients enrolled in the Clinical Practice Research Datalink, as well as hospital electronic health records. Patient inclusion criteria required an individual to be 18 years or older, have undergone a follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and to not have osteoporosis at baseline.

The exposure used in the study was adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs, with the outcome of incident osteoporosis defined through Cox proportional hazard models or accelerated failure time models. The analysis used controls for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index (BMI), bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests.

Additionally, subsequent analyses excluded BMI, used propensity score matching for receipt of an eiASM, restricted analyses to only those with incident onset epilepsy, and restricted analyses to patients who developed epilepsy at ages 65 and older. All analyses were performed between July 1, 2022, and October 31, 2022, with revisions in February 2023.

A total of 8,094,441 individuals were identified, in which 6275 had incident adult-onset epilepsy. Of these individuals, 3220 (51%) were female. The incidence rate was 62 per 100,000 person-years and the median age was 56 (38-73) years.

When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P < .001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P < .001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P < .001) were associated with significantly increased risks independent of epilepsy and accounted for 9% and 23% faster time to development of osteoporosis, respectively.

The researchers acknowledged some limitations to the study, including assuming all individuals taking 4 consecutive ASMs continued with this class of medication, the median prescription time was 9 years, and the lack of specificity of epilepsy type, seizure type, and seizure frequency.

Despite these limitations, the researchers believe the study shows an association between epilepsy, ASM use, and the risk of osteoporosis, and suggests the implementation of routine screening and prophylaxis among patients with epilepsy to mitigate this risk.

“This cohort study shows a clear and robust association between incident adult-onset epilepsy and incident osteoporosis, independent of medications, common risk factors, fragility fractures, and falls,” wrote the researchers. “The findings also showed clear associations between both eiASM and non-eiASM use and incident osteoporosis, independent of incident epilepsy.”

Reference

Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S. Independent associations of incident epilepsy and enzyme-inducing and non–enzyme-inducing antiseizure medications with the development of osteoporosis. JAMA Neurol. 2023;80(8):843-850. doi:10.1001/jamaneurol.2023.1580