Endogenous DHEAS is Causally Linked with Lumbar Spine Bone Mineral Density and Forearm Fractures in Women.

• A recent pooled analysis of four clinical trials demonstrated that treatment with dehydroepiandrosterone (DHEA) increases lumbar spine BMD (LS-BMD) in women. The causal effect of endogenous adrenal-derived DHEA-sulphate (DHEAS) on LS-BMD and fracture risk in women is unknown.To determine whether circulating DHEAS is causally associated with LS-BMD and fracture risk in women.A two-sample mendelian randomization study using genetic predictors of serum DHEAS derived from the largest available female-specific genome wide association study (GWAS) meta-analysis (n=8 565). Genetic associations with DXA-derived BMD (n=22 900) were obtained from female specific GWAS summary statistics available from the GEFOS consortium while individual-level data of 238 565 women of white ancestry from the UK Biobank were used for associations with fractures (11 564 forearm fractures, 2 604 hip fractures) and estimated heel BMD by ultrasound (eBMD).A 1 standard deviation (SD) genetically instrumented increase in log serum DHEAS levels was associated with a 0.21 SD increase in LS-BMD (P-value: 0.01) and a 0.08 SD increase in eBMD (P-value: <0.001). Genetically predicted DHEAS decreased forearm fracture risk (odds ratio (OR): 0.70, 95% confidence interval (CI): 0.55-0.88 per SD increase in DHEAS) while no significant causal association with hip fractures was observed.Genetically predicted serum DHEAS increases LS-BMD and decreases forearm fracture risk in women. Based on the results of the present study and previous RCTs of DHEA treatment, we propose that both endogenous adrenal-derived DHEA(S) and pharmacological DHEA treatment improve bone health in women.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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