How safe is bone health in patients on newer or enzyme inhibitor antiepileptic drugs?

Abstract

Background: Data on the effect of enzyme inhibitors and newer anti-epileptic drugs (AEDs) on bone health is limited with conflicting results.

Aim: We compared the effects on bone health of patients exposed to enzyme inducer versus enzyme inhibitor AEDs and newer versus older AEDs.

Methods: We prospectively studied 51 patients on AEDs for more than two years and equal age and sex matched controls from March 2017 to September 2018. Biochemical bone mineral markers and bone mineral density (BMD) were measured and analysed between patients versus controls and between various sub-groups based on enzymatic effect, generation and number of AEDs.

Results: Of 51 patients,11(21.5%) had osteopenia and 3(5.9%) had osteoporosis. T-score (-0.75 ± 1.22 versus 0.004 ± 1.0, p < .001) and Z-score at femur neck (-0.38 ± 1.08 versus0.002 ± 0.81, p < .001) were found to be significantly lower in patients compared to controls. Relative risk for low BMD was higher in patients on polytherapy compared to monotherapy (RR = 1.37,CI = 0.69-2.74).Higher relative risk for low BMD was noted with; clobazam (RR = 1.51,CI = 0.82-2.78), oxcarbazepine (RR = 1.33,CI = 0.68-2.59), phenobarbitone (RR = 1.31,CI = 0.26-6.7) and leviteracetam (RR = 1.18,CI = 0.45-3.06) mono or polytherapy and valproate monotherapy (RR = 3.5,CI = 1.09-11.29). No significant difference was noted with regards to mean dosage or metabolic or radiological markers of bone health between patients on enzyme inducer versus inhibitors and newer versus older AEDs. A significant negative correlation was found between cumulative drug load and femur T-score (r2 = -0.27, p = .04).

Conclusion: Bone health in epilepsy is adversely affected by chronic exposure to AEDs; irrespective of the enzymatic effect or generation of AEDs. Complex pharmacodynamic mechanisms of AEDs as well as pharmacokinetic interactions between various AED polytherapies affects bone health.

Keywords: Antiepileptic drugs; Bone health; DEXA; Enzyme inducers/inhibitors.