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

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.