High SHBG and low bioavailable testosterone are strongly causally associated with increased forearm fracture risk in women: an MR study leveraging novel female-specific data Visa övriga samt affilieringar
2024 (Engelska) Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 115, nr 5, s. 648-660Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
The effects of androgens on women’s bone health are not fully understood. Mendelian randomization (MR) studies using sex-combined data suggest that sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT) causally affect bone traits. Given significant sex differences in hormone regulation and effects, female-specific MR studies are necessary. In the current study, we explored the causal relationships of SHBG, BioT, and total testosterone (TT) with forearm fracture (FAFx) risk in women using two-sample MR analyses. We utilized a unique female-specific FAFx outcome dataset from three European biobanks (UFO, HUNT, Estonian Biobank) comprising 111,351 women and 8823 FAFx cases, along with female-specific genetic instruments of SHBG, BioT, and TT identified in the UK Biobank. We also assessed bone mineral density (BMD) at the forearm (FA), femoral neck (FN), and lumbar spine (LS) using female-specific GWAS data from the GEFOS consortium. High SHBG (odds ratio per standard deviation increase (OR/SD): 1.53, 95% confidence intervals (CIs): 1.34–1.75), low BioT (OR/SD: 0.77, 0.71–0.84) and low TT (OR/SD 0.90, 0.83–0.98) were causally associated with increased FAFx risk. BioT was positively, and SHBG inversely, causally associated with especially FA-BMD, but also LS-BMD and FN-BMD, while TT was only significantly positively associated with FA-BMD and LS-BMD. We propose that endogenous androgens and SHBG are important for women’s bone health at distal trabecular-rich bone sites such as the distal forearm and may serve as predictors for FAFx risk.
Ort, förlag, år, upplaga, sidor Springer Nature, 2024. Vol. 115, nr 5, s. 648-660
Nyckelord [en]
Bone, Bone density, Female, Fractures, Mendelian randomization analysis, Sex hormone-binding globulin, Testosterone
Nationell ämneskategori
Ortopedi Endokrinologi och diabetes
Identifikatorer URN: urn:nbn:se:umu:diva-231779 DOI: 10.1007/s00223-024-01301-5 ISI: 001335123800002 PubMedID: 39412545 Scopus ID: 2-s2.0-85206917254 OAI: oai:DiVA.org:umu-231779 DiVA, id: diva2:1915423
Forskningsfinansiär Europeiska regionala utvecklingsfonden (ERUF), 2014-2020.4.01.15-0012 Vetenskapsrådet, 2020-01392 Vetenskapsrådet, 2016-01001 Sveriges Kommuner och Regioner, SKR, ALFGBG-720331 Sveriges Kommuner och Regioner, SKR, ALFGBG-965235 Novo Nordisk fonden, NNF 190C0055250 Knut och Alice Wallenbergs Stiftelse, KAW2015.0317 2024-11-222024-11-222024-11-22 Bibliografiskt granskad