Chang PY, et al. - A nested case-cohort study of 868 postmenopausal women was conducted within the Women's Health Initiative Hormone Therapy (WHI-HT) trials to assess the impact of 27-Hydroxycholesterol (27HC) in fracture risk. The WHI-HT tested conjugated equine estrogens vs placebo and independently conjugated equine estrogens plus progestin vs placebo. They estimated with Cox models, the hazard ratios for the incident fracture to pre-randomization circulating levels of 27HC and 27HC/bioavailable 17β-estradiol (bioE₂) molar ratio. Criteria included were age, race/ethnicity, total cholesterol, bioE₂, sex hormone-binding globulin, 25-hydroxyvitamin D, diabetes, osteoporosis, prior menopausal hormone therapy (MHT) use, BMI, fall history, and prior fracture. Females who were allocated to placebo arms, those in the middle and the highest tertiles of 27HC/bioE₂ were found with up to 1.9-fold greater risk of fracture. The fracture risk reduction was not altered by 27HC and 27HC/bioE₂ in MHT.