Evidence of a causal effect of estradiol on fracture risk in men
Journal article
Nethander, Maria, Vandenput, Liesbeth, Eriksson, Anna L., Windahl, Sara, Funck-Brentano, Thomas and Ohlsson, Claes. (2019). Evidence of a causal effect of estradiol on fracture risk in men. The Journal of Clinical Endocrinology and Metabolism. 104(2), pp. 433 - 442. https://doi.org/10.1210/jc.2018-00934
Authors | Nethander, Maria, Vandenput, Liesbeth, Eriksson, Anna L., Windahl, Sara, Funck-Brentano, Thomas and Ohlsson, Claes |
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Abstract | Context: Observational studies indicate that serum estradiol (E2) is more strongly associated with bone mineral density (BMD) than serum testosterone (T) is, whereas both E2 and T associate with fracture risk in men. Objective: To evaluate the possible causal effect of serum E2 and T on fracture risk in men. Design, Setting, and Participants: A Mendelian randomization (MR) approach was undertaken using individual-level data on genotypes, BMD as estimated by quantitative ultrasound of the heel (eBMD), fractures (n = 17,650), and relevant covariates of 175,583 unrelated men of European origin from the UK Biobank. The genetic instruments for serum E2 and T were taken from the most recent large-scale genome-wide association study meta-analyses on these hormones in men. Results: MR analyses demonstrated a causal effect of serum E2 on eBMD and fracture risk. A 1 SD (or 9.6 pg/mL) genetically instrumented decrease in serum E2 levels was associated with a 0.38 SD decrease in eBMD (P value: 9.7 × 10−74) and an increased risk of any fracture (OR: 1.35; 95% CI: 1.18, 1.55), nonvertebral major osteoporotic fractures (OR: 1.75; 95% CI: 1.35, 2.27), and wrist fractures (OR: 2.27; 95% CI: 1.62, 3.16). These causal effects of serum E2 levels on fracture risk were robust in sensitivity analyses and remained unchanged in stratified analyses for age, body mass index, eBMD, smoking status, and physical activity. MR analyses revealed no evidence of a causal effect of T levels on fracture risk. Conclusion: Our findings provide evidence of a robust causal effect of serum E2, but not T, on fracture risk in men. |
Year | 2019 |
Journal | The Journal of Clinical Endocrinology and Metabolism |
Journal citation | 104 (2), pp. 433 - 442 |
Publisher | Oxford University Press |
ISSN | 0021-972X |
Digital Object Identifier (DOI) | https://doi.org/10.1210/jc.2018-00934 |
Scopus EID | 2-s2.0-85059236673 |
Page range | 433 - 442 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/89y5z/evidence-of-a-causal-effect-of-estradiol-on-fracture-risk-in-men
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