Koh Eileen H, Ewing Susan K, Sigurdsson Sigurdur, Gudnason Vilmundur, Hue Trisha F, Vittinghoff Eric, Ohlsson Claes, Tivesten Åsa, Grahnemo Louise, Yuen Tony, Zaidi Mone, Rosen Clifford J, Schwartz Ann V, Schafer Anne L
Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
J Clin Endocrinol Metab. 2024 Oct 12. doi: 10.1210/clinem/dgae690.
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.
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.
Incident hip fracture.
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].
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.
在围绝经期过渡阶段的女性以及老年男性中，促卵泡激素（FSH）水平升高与骨质流失相关，且独立于雌二醇和睾酮水平，但较高的FSH是否为独立的骨折风险因素尚不清楚。
确定基线FSH水平是否能预测老年人随后发生的髋部骨折。
设置、设计、参与者：采用病例队列设计，我们从年龄、基因/环境易感性（AGES）-雷克雅未克队列中按性别分层随机抽取了295名参与者，其中包括25名在基线后10年内发生髋部骨折的参与者。我们另外抽取了230名发生髋部骨折的按性别分层的参与者。在基线时测量血清FSH和性激素水平。采用稳健加权Cox比例风险模型来确定FSH与髋部骨折风险之间的关系。
发生髋部骨折。
由于未发现FSH与性别之间在与骨折关系上存在相互作用，因此将男性和女性合并进行分析。在根据年龄和性别进行调整的模型中，较高的FSH水平与发生髋部骨折的风险显著增加相关[风险比（HR）为1.24（95%置信区间为1.04 - 1.48，p = 0.02）]，在进一步根据雌二醇、睾酮和性激素结合球蛋白水平进行调整后[FSH水平每增加一个性别特异性标准差，HR为1.20（95%置信区间为1.01 - 1.44，p = 0.04）]。
较高的FSH与随后发生髋部骨折的风险增加相关。我们的研究结果支持了越来越多的证据，表明FSH对骨骼具有直接的多效性作用，并且FSH在衰老和残疾过程中发挥作用，独立于性激素水平。
