Concentration and genetic regulation of sex hormone binding globulin and fracture risk in older women

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Abstract

Objective: This study aimed to examine the association between concentrations of sex hormone binding globulin (SHBG) and fracture risk in community-dwelling older women and explore whether this was explained by the genetic regulation of SHBG. Methods: This prospective cohort study examined 4871 women aged ≥70 years who were not taking medications influencing SHBG concentrations. A genome-wide association study was undertaken to identify single nucleotide polymorphisms (SNPs) associated with SHBG concentrations. Incident fracture was confirmed by medical imaging and adjudicated by expert review committee. Results: The median age of participants was 74.0 years. Over 3.9 (standard deviation 1.4) years of follow-up, 484 participants had an incident fracture. There was a linear trend for a positive association between SHBG concentrations and fracture risk (p = 0.001), with the highest SHBG quartile associated with a significantly greater fracture risk compared with the lowest quartile (hazard ratio 1.54, 95% confidence interval 1.16–2.04, p = 0.003), adjusting for age, body mass index, alcohol consumption, smoking, diabetes, impaired renal function, treatment allocation, medications affecting bone and high-density lipoprotein cholesterol. Two independent SNPs were associated with SHBG concentrations, rs10822163 and rs727428, but neither was associated with fracture risk. Conclusion: SHBG concentrations were positively associated with a greater fracture risk in community-dwelling women aged ≥70 years, which was not explained by genetic variants associated with SHBG regulation.

Original languageEnglish
Number of pages7
JournalClimacteric
DOIs
Publication statusAccepted/In press - 2024

Keywords

  • fracture
  • genome-wide association study
  • older women
  • Sex hormone binding globulin

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