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.
Bone
Bone density
Female
Fractures
Mendelian randomization analysis
Sex hormone-binding globulin
Testosterone
Journal
Calcified tissue international
ISSN: 1432-0827
Titre abrégé: Calcif Tissue Int
Pays: United States
ID NLM: 7905481
Informations de publication
Date de publication:
16 Oct 2024
16 Oct 2024
Historique:
received:
31
07
2024
accepted:
27
09
2024
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
16
10
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 39412545
doi: 10.1007/s00223-024-01301-5
pii: 10.1007/s00223-024-01301-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Vetenskapsrådet
ID : 2020-01392
Organisme : Vetenskapsrådet
ID : 2016-01001
Organisme : the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement
ID : ALFGBG-720331
Organisme : the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement
ID : ALFGBG-965235
Organisme : IngaBritt och Arne Lundbergs Forskningsstiftelse
ID : LU2021-0096
Organisme : IngaBritt och Arne Lundbergs Forskningsstiftelse
ID : LU2017-0081
Organisme : Novo Nordisk Fonden
ID : NNF 190C0055250
Organisme : Knut och Alice Wallenbergs Stiftelse
ID : KAW2015.0317
Investigateurs
Andres Metspalu
(A)
Lili Milani
(L)
Tõnu Esko
(T)
Reedik Mägi
(R)
Mari Nelis
(M)
Georgi Hudjashov
(G)
Informations de copyright
© 2024. The Author(s).
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