A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: The Tromsøo Study

Objectives: As bone fragility is partly the result of sex hormone deficiency, we sought to determine whether circulating sex steroids or sex hormone-binding globulin (SHBG) predicts non-vertebral fractures. Methods: Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels, and SHBG were measured in 1386 postmenopausal women and 1364 men aged 50-84 years at baseline in the Tromsø Study (1994-1995). Non-vertebral fractures were documented between 1994 and 2005. Results: During 8.4 years (range 0.01-10.4) of follow-up, 281 women and 105 men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD and higher SHBG, but sex steroids were not lower. Each standard deviation (S.D.) increase in SHBG increased non-vertebral fracture risk in women (hazards ratio (HR) 1.17; 95% confidence interval (CI) 1.03-1.33) and men (HR 1.26; 95% CI 1.03-1.54). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95%CIO.95-1.24) or men (HR 1.22; 95% CI 0.99-1.49). Each S.D. decrease in BMD increased fracture risk in women (HR 1.36; 95%CI 1.19-1.56) and men (HR 1.41; 95% CI 1.15-1.73). Fracture rates were highest in participants with SHBG in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1000 person-years in women and men respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone. Sex steroids were not associated with fracture risk. Conclusions: Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.