Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study.

Karl Michaëlsson,Susanna C Larsson

doi:10.3390/nu13061940

Karl Michaëlsson, Susanna C Larsson

Open Access

https://doi.org/10.3390/nu13061940

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Journal: Nutrients	Publication Date: Jun 5, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Uppsala University, Karolinska Institutet

Abstract

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10−8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm2 increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.

Highlights

Worldwide, 1.6 million hip fractures are estimated to occur each year [1] at an average of 80 years of age
The association estimates were adjusted for age, cancer status, and body mass index and, because it is well recognized that vitamin E levels are influenced by blood lipids, additional adjustment was made for total and high-density lipoprotein cholesterol
The of characteristics of the three SNPs withand α-tocopherol and their associaThe characteristics the three SNPs associated withassociated α-tocopherol their associations estimated bone mineral density (eBMD)

Summary

Introduction

1.6 million hip fractures are estimated to occur each year [1] at an average of 80 years of age. There is a higher risk of death after the fracture event [2], and especially vulnerable are older men [2]. Scandinavia has one of the highest incidences of fragility fractures in the world, with a lifetime cumulative incidence of 50% in women and 25% in men [3,4]. The risk of hip fracture, the most devastating fragility fracture, increases 44-fold in Swedish women from 55 to 85 years of age, so that the lifetime risk of hip fracture is 25% in women and 12% in men [4]. Bone mineral density (BMD) is a strong determinant of future risk of hip fracture. Hip fracture rates are more than doubled for each standard-deviation lower BMD at the hip [5], whereas the association between other BMD and fractures sites is generally less strong [5,6]

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Conclusion