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27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative.

Publication ,  Journal Article
Chang, P-Y; Feldman, D; Stefanick, ML; McDonnell, DP; Thompson, BM; McDonald, JG; Lee, JS
Published in: J Bone Miner Res
January 2019

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.

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Published In

J Bone Miner Res

DOI

EISSN

1523-4681

Publication Date

January 2019

Volume

34

Issue

1

Start / End Page

59 / 66

Location

United States

Related Subject Headings

  • Spinal Fractures
  • Selective Estrogen Receptor Modulators
  • Risk Factors
  • Prospective Studies
  • Progestins
  • Postmenopause
  • Middle Aged
  • Hydroxycholesterols
  • Humans
  • Hip Fractures
 

Citation

APA
Chicago
ICMJE
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Chang, P.-Y., Feldman, D., Stefanick, M. L., McDonnell, D. P., Thompson, B. M., McDonald, J. G., & Lee, J. S. (2019). 27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative. J Bone Miner Res, 34(1), 59–66. https://doi.org/10.1002/jbmr.3576
Chang, Po-Yin, David Feldman, Marcia L. Stefanick, Donald P. McDonnell, Bonne M. Thompson, Jeffrey G. McDonald, and Jennifer S. Lee. “27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative.J Bone Miner Res 34, no. 1 (January 2019): 59–66. https://doi.org/10.1002/jbmr.3576.
Chang P-Y, Feldman D, Stefanick ML, McDonnell DP, Thompson BM, McDonald JG, et al. 27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative. J Bone Miner Res. 2019 Jan;34(1):59–66.
Chang, Po-Yin, et al. “27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative.J Bone Miner Res, vol. 34, no. 1, Jan. 2019, pp. 59–66. Pubmed, doi:10.1002/jbmr.3576.
Chang P-Y, Feldman D, Stefanick ML, McDonnell DP, Thompson BM, McDonald JG, Lee JS. 27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative. J Bone Miner Res. 2019 Jan;34(1):59–66.
Journal cover image

Published In

J Bone Miner Res

DOI

EISSN

1523-4681

Publication Date

January 2019

Volume

34

Issue

1

Start / End Page

59 / 66

Location

United States

Related Subject Headings

  • Spinal Fractures
  • Selective Estrogen Receptor Modulators
  • Risk Factors
  • Prospective Studies
  • Progestins
  • Postmenopause
  • Middle Aged
  • Hydroxycholesterols
  • Humans
  • Hip Fractures