Higher FSH Level is Associated with Increased Risk of Incident Hip Fracture in Older Adults, Independent of Sex Hormones

CONTEXT:Higher levels of FSH are associated with bone loss among women during the perimenopausal transition and among older men, independent of estradiol and testosterone levels, but whether higher FSH is an independent fracture risk factor is unknown. OBJECTIVE:Determine whether baseline FSH level predicts subsequent hip fracture in older adults. SETTING, DESIGN, PARTICIPANTS:Using a case-cohort design, we randomly sampled 295 participants stratified by sex from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort, including 25 participants with incident hip fracture within 10 years after baseline. We sampled an additional 230 sex-stratified participants with incident hip fracture. Serum FSH and sex hormone levels were measured at baseline. Robust weighted Cox proportional hazards models were used to determine the relationship between FSH and hip fracture risk. MAIN OUTCOME:Incident hip fracture. RESULTS:As no interaction was identified between FSH and sex for the relationship with fracture, men and women were pooled for analysis. Higher levels of FSH were associated with a significantly increased risk of incident hip fracture in models adjusted for age and sex [hazard ratio (HR) 1.24 (95% CI 1.04-1.48, p=0.02)] and after further adjustment for estradiol, testosterone, and sex hormone binding globulin levels [HR 1.20 (95% CI 1.01-1.44, p=0.04) per sex-specific SD increase in FSH level]. CONCLUSIONS:Higher FSH is associated with increased risk of subsequent hip fracture. Our findings support a growing body of evidence for direct pleiotropic effects of FSH on bone, and for a role for FSH in aging and disability independent of sex hormone levels.