A novel index to assess low energy fracture risks in patients prescribed antiepileptic drugs

Abstract

Objective To develop an index assessing the risks of low energy fractures (LEF) in patients prescribed antiepileptic drugs (AED) by exploring five previously suggested risk factors; age, gender, AED-type, epilepsy diagnosis and BMI. Methods In a population-based retrospective open cohort study we used real world data from the Electronic Health Register (EHR) in Region Kalmar County, Sweden. 23 209 patients prescribed AEDs at any time from January 2008 to November 2018 and 23 281 matching controls were followed from first registration in the EHR until the first documented LEF, disenrollment (or death) or until the end of the study period, whichever came first. Risks of LEF measured as hazard rate ratios in relation to the suggested risk factors and in comparison to matched controls were analyzed using Cox regression. The index was developed using a linear combination of the statistically significant variables multiplied by the corresponding regression coefficients. Results Data from 23 209 patients prescribed AEDs and 2084 documented LEFs during a follow-up time of more than 10 years resulted in the Kalmar Epilepsy Fracture Risk Index (KEFRI). KEFRI = Age-category x (1.18) + Gender x (-0.51) + AED-type x (0.29) + Epilepsy diagnosis-category x (0.31) + BMI-category x (-0.35). All five previously suggested risk factors were confirmed. Women aged 75 years and older treated with an inducing AED against epilepsy and BMIs of 25 kg/m2 or below had 48 times higher LEF rates compared to men aged 50 years or younger, treated with a non-inducing AED for a condition other than epilepsy and BMIs above 25 kg/m2. Conclusion The KEFRI is the first weighted multifactorial assessment tool estimating risks of LEF in patients prescribed AEDs and could serve as a feasible guide within clinical practice.