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Endogenous Estradiol and The Risk of Incident Fracture in Postmenopausal Women: The OPUS Study

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Abstract

Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E2, SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52–5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E2. Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E2, bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E2, SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E2 at vertebral compared with nonvertebral sites.

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Acknowledgments

The OPUS study was sponsored by Eli Lilly, Sanofi-aventis, Procter & Gamble Pharmaceuticals, Hoffman-La Roche, Pfizer, and Novartis. We acknowledge the support of the National Institute for Health Research, UK, via its Biomedical Research Units funding scheme. The authors acknowledge Richard Jacques and Mike Bradburn, University of Sheffield School of Health and Related Research, for their statistical advice.

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Authors and Affiliations

  1. Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK

    J. Finigan, F. Gossiel & R. Eastell

  2. Sektion Biomedizinische Bildgebung, Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany

    C. C. Glüer

  3. Zentrum für Muskel- & Knochenforschung, Charité - Universitätsmedizin Berlin, Berlin, Germany

    D. Felsenberg

  4. School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK

    D. M. Reid

  5. Cochin Hospital, Paris Descartes University, Paris, France

    C. Roux

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  1. J. Finigan
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Correspondence to J. Finigan.

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The authors have stated that they have no conflict of interest.

The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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Finigan, J., Gossiel, F., Glüer, C.C. et al. Endogenous Estradiol and The Risk of Incident Fracture in Postmenopausal Women: The OPUS Study. Calcif Tissue Int 91, 59–68 (2012). https://doi.org/10.1007/s00223-012-9611-8

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  • DOI: https://doi.org/10.1007/s00223-012-9611-8

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