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

Ola Nordqvist,Olof Björneld,Rebecca Nobin,Lars Brudin,Martin Carlsson,Pär Wanby,Robert Daniel Blank

doi:10.1371/journal.pone.0256093

Ola Nordqvist, Olof Björneld + Show 5 more

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https://doi.org/10.1371/journal.pone.0256093

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Abstract

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. 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. 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. 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.

Highlights

With an ageing population worldwide, the number of low energy fractures (LEF) is expected to increase from the 9 million annual fractures registered at the turn of the century [1]
Data from 23 209 patients prescribed antiepileptic drugs (AED) and 2084 documented LEFs during a follow-up time of more than 10 years resulted in the Kalmar Epilepsy Fracture Risk Index (KEFRI)
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

Summary

Introduction

With an ageing population worldwide, the number of low energy fractures (LEF) is expected to increase from the 9 million annual fractures registered at the turn of the century [1]. These fractures cause both suffering and generate considerable health care costs [2]. Risk factors for LEFs have been assessed in several epidemiological studies [3, 4], resulting in the development of general risk assessment tools being used in clinical practice One of these tools is FRAX1, which integrates eight clinical risk factors in estimating the 10-year major osteoporotic fracture risk [5]. The only drug class included in FRAX1 at present is glucocorticoids

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