Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
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
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Show others and affiliations
2024 (English)In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 115, no 5, p. 648-660Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Springer Nature, 2024. Vol. 115, no 5, p. 648-660
Keywords [en]
Bone, Bone density, Female, Fractures, Mendelian randomization analysis, Sex hormone-binding globulin, Testosterone
National Category
Orthopaedics Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:umu:diva-231779DOI: 10.1007/s00223-024-01301-5ISI: 001335123800002PubMedID: 39412545Scopus ID: 2-s2.0-85206917254OAI: oai:DiVA.org:umu-231779DiVA, id: diva2:1915423
Funder
European Regional Development Fund (ERDF), 2014-2020.4.01.15-0012Swedish Research Council, 2020-01392Swedish Research Council, 2016-01001Swedish Association of Local Authorities and Regions, ALFGBG-720331Swedish Association of Local Authorities and Regions, ALFGBG-965235Novo Nordisk Foundation, NNF 190C0055250Knut and Alice Wallenberg Foundation, KAW2015.0317Available from: 2024-11-22 Created: 2024-11-22 Last updated: 2024-11-22Bibliographically approved

Open Access in DiVA

fulltext(1083 kB)19 downloads
File information
File name FULLTEXT01.pdfFile size 1083 kBChecksum SHA-512
150ff28942817e1b5ff3c357d0ccbf8cb112d94bd901c0359be698a4ff51ad4950df5aa876c22daf65ee1d26e71d34a36cb63200387a0569f24b270c306d2ddb
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Pettersson-Kymmer, Ulrika

Search in DiVA

By author/editor
Pettersson-Kymmer, Ulrika
By organisation
Department of Medical and Translational BiologyClinical Pharmacology
In the same journal
Calcified Tissue International
OrthopaedicsEndocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar
Total: 19 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 174 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf