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 ( = 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,  = 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.