Sex hormone-binding globulin and risk of fracture in older adults: systematic review and meta-analysis of observational studies

Summary We conducted a meta-analysis of observational study to clarify the association between sex hormone-binding globulin (SHBG) levels and the risk of fracture in older adults. We found that higher SHBG levels were associated with an increased risk of fracture in older adults. Introduction The association between SHBG levels and the risk of fracture in older adults remains elusive. We aim to clarify this association by conducting a meta-analysis of observational studies. Methods PubMed and Web of Science databases were searched for relevant observational studies investigating the association between SHBG levels and the risk of fracture in older adults. The relative risks (RRs) with 95% confidence intervals (CIs) from each study were transformed into a continuous variable for each 1 μg/dL increase in SHBG and were pooled under a random-effects model. Results A total of 16 observational studies were included in the present meta-analysis. The summary RR of fracture risk associated with each 1 μg/dL increase in SHBG was 1.18 (95% CI 1.11, 1.26); no statistically significant heterogeneity was observed across studies ( I 2 = 0%, P = 0.67). The positive association was also evident in men (RR 1.22, 95% CI 1.12, 1.33) and women (RR 1.15, 95% CI, 1.05, 1.26). By site of fracture, higher SHBG levels were positively associated with higher risks of hip fracture (RR 1.43, 95% CI 1.23, 1.65), vertebral fracture (RR 1.31, 95% CI 1.12, 1.54), and non-vertebral fracture (RR 1.21, 95% CI 1.06, 1.38). Conclusions The present meta-analysis suggests that higher SHBG levels predict an increased risk of fracture in older adults. Further studies should aim to elucidate the complex biological mechanisms by which SHBG may affect fracture risk.