Associations Between Serum Sodium Concentration and Bone Health Measures in Individuals Who Use Antiepileptic Drugs : A Pilot Study

Hyponatraemia, defined as a serum sodium concentration ([Na+]) below 135 mmol/L, is the most common electrolyte disturbance observed in clinical practice (1). Hyponatraemia is associated with increased risk of osteoporosis (2,3), fractures (4,5), fractures independent of osteoporosis (3,5), and falls (4).

One of the common medication classes that cause hyponatraemia is antiepileptic drugs (AEDs), which are often used lifelong in patients with epilepsy, and increasingly in other conditions. AEDs can be classified as hepatic CYP450 enzyme-inducing AEDs (EIAEDs) or non-enzyme-inducing AEDs (NEIAEDs). Certain AEDs, such as carbamazepine and oxcarbazepine, demonstrate stronger associations with hyponatraemia than other AEDs (6). Whilst inducing hyponatraemia, AEDs are also independently associated with increased risk of osteoporosis and fracture (7). However, the underlying mechanisms by which AEDs adversely affect the risk of fragility fracture, and also cause hyponatraemia remain uncertain and likely are multifactorial.

A potential association between serum sodium concentration and the risk of fragility fracture in AED users appears not to have been explored previously and could help explain how AEDs are associated with impaired bone health. In this pilot study, we investigated the associations between the risk of fragility fracture (indicated by areal BMD (aBMD), fracture history, and falls history), and serum sodium concentrations in AED users. We hypothesised that AED use is associated with hyponatraemia, which is also associated with low aBMD and an increase in reported history of fractures and falls.

Materials and Methods: This was a retrospective study including patients with epilepsy from 3 studies approved by the Human Research Ethics Committee (HREC) at Melbourne Health, Victoria, Australia. All participants provided written consent to participate in the studies.