Epilepsy and osteoporosis

Epilepsy and osteoporosis

A cohort study (n=6275) found both the development of epilepsy (independent of antiseizure medication [ASM] use) and use of ASM (independent of epilepsy and irrespective of enzyme-inducing capacity) were associated with increased hazards for osteoporosis (1)

• study collected data on 6275 adults with incident adult-onset epilepsy, enrolled in the Clinical Practice Research Datalink. Analyses controlling for osteoporosis risk factors noted the following:
  • 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<0.001)
    
    
  • both enzyme-inducing (TR, 0.91; 95% CI, 0.87-0.95; P<0.001) and non-enzyme inducing ASMs (TR, 0.77; 95% CI, 0.76-0.78; P<0.001) were associated with increased risks, independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively
    
    
  • authors conclude, based on their findings, that routine osteoporosis screening and prophylaxis should be considered in all people with epilepsy

Previously noted (2):

• studies have shown a significant reduction in bone mineral density (BMD) and an increased fracture risk in patients treated with enzyme-inducing antiepileptics (phenobarbital, carbamazepine, phenytoin)
  • assumed that CYP450-inducing antiepileptic drugs (AEDs) upregulate the enzymes which are responsible for vitamin D metabolism, with the effect of converting 25(OH) vitamin D into inactive metabolites, resulting in reduced calcium absorption with consecutive secondary hyperparathyroidism
  • for patients with long-term AED exposure, BMD measurement is recommended as part of osteoporosis investigation (especially for patients treated with enzyme-inducing AEDs and where there are major risk factors for fractures)

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. Published online June 12, 2023. doi:10.1001/jamaneurol.2023.1580
• Meier C, Kraenzlin ME. Antiepileptics and bone health. Ther Adv Musculoskelet Dis. 2011 Oct;3(5):235-43. doi: 10.1177/1759720X11410769. PMID: 22870482; PMCID: PMC3383529.