27-羟基胆固醇(27HC)是一种所谓的,新型内源性SERM。在动物模型中,27HC在骨骼中具有抗雌激素作用,17β-雌二醇减轻了这种作用。27HC与骨折风险的关系尚未在人类中进行研究。根据生物可利用的17β-雌二醇(bioE2)的水平,27HC可能会增加绝经后妇女的骨折风险,并改变绝经激素治疗(MHT)的骨折风险降低。为了测试这些先验假设,我们在妇女健康倡议激素治疗(WHI-HT)试验中对868名绝经后妇女进行了嵌套病例队列研究.WHI-HT测试了缀合的马雌激素与安慰剂的比较,以及分别缀合的马雌激素加孕激素与安慰剂的比较。骨折病例为442名女性,在WHI-HT随访期间发生了经裁定的髋部或临床椎骨骨折。该亚组包括在WHI-HT基线时随机选择的430名女性,其中四人随后骨折。868名女性中,266例和219例非病例被分配到安慰剂组。Cox模型估计了与27HC和27HC/bioE2摩尔比的随机化前循环水平相关的意外骨折的危险比。根据年龄调整的模型,种族/民族,总胆固醇,bioE2,性激素结合球蛋白,25-羟基维生素D,糖尿病,骨质疏松,以前使用MHT,BMI,瀑布历史,和先前的骨折。在分配给安慰剂组的女性中,27HC/bioE2的中间和最高三分位数的人高达1.9倍(95%置信区间,1.25至2.99)的骨折风险比最低三分位数的女性更大。在分配给MHT武器的妇女中,骨折风险随27HC/bioE2连续水平的增加而增加,但与分类水平无关.仅27HC水平与骨折风险无关。27HC和27HC/bioE2没有改变MHT的骨折风险降低。在绝经后的女性中,27HC相对于bioE2的循环水平可以识别骨折风险增加的人群。©2018美国骨骼和矿物质研究协会。
27-Hydroxycholesterol (27HC) is a purported, novel endogenous SERM. In animal models, 27HC has an anti-estrogen effect in bone, and 17β-estradiol mitigates this effect. 27HC in relation to fracture risk has not been investigated in humans. Depending on the level of bioavailable 17β-estradiol (bioE2 ), 27HC may increase fracture risk in postmenopausal women and modify the fracture risk reduction from menopausal hormone therapy (MHT). To test these a priori hypotheses, we conducted a nested
case-cohort study of 868 postmenopausal women within the Women\'s Health Initiative Hormone Therapy (WHI-HT) trials. The WHI-HT tested conjugated equine estrogens versus placebo and separately conjugated equine estrogens plus progestin versus placebo. Fracture cases were 442 women who had an adjudicated incident hip or clinical vertebral fracture during the WHI-HT follow-up. The subcohort included 430 women randomly selected at WHI-HT baseline, four of whom had a subsequent fracture. Of the 868 women, 266 cases and 219 non-cases were assigned to the placebo arms. Cox models estimated hazard ratios for incident fracture in relation to pre-randomization circulating levels of 27HC and 27HC/bioE2 molar ratio. Models adjusted for age, race/ethnicity, total cholesterol, bioE2 , sex hormone-binding globulin, 25-hydroxyvitamin D, diabetes, osteoporosis, prior MHT use, BMI, falls history, and prior fracture. In women assigned to placebo arms, those in the middle and the highest tertiles of 27HC/bioE2 had an up to 1.9-fold (95% confidence intervals, 1.25 to 2.99) greater risk of fracture than women in the lowest tertile. In women assigned to MHT arms, fracture risk increased with continuous 27HC/bioE2 levels but not with categorical levels. 27HC levels alone were not associated with fracture risk. 27HC and 27HC/bioE2 did not modify the fracture risk reduction from MHT. In postmenopausal women, circulating levels of 27HC relative to bioE2 may identify those at increased risk of fracture. © 2018 American Society for Bone and Mineral Research.