Older Men With Low Serum Estradiol and High Serum SHBG Have an Increased Risk of Fractures

Authors

  • Dan Mellström,

    1. Center for Bone Research at the Sahlgrenska Academy, Departments of Internal Medicine and Geriatrics, University of Gothenburg, Gothenburg, Sweden
    2. These authors contributed equally to this work
    Search for more papers by this author
  • Liesbeth Vandenput,

    1. Center for Bone Research at the Sahlgrenska Academy, Departments of Internal Medicine and Geriatrics, University of Gothenburg, Gothenburg, Sweden
    2. These authors contributed equally to this work
    Search for more papers by this author
  • Hans Mallmin,

    1. Department of Medical Sciences, University of Uppsala, Uppsala, Sweden
    Search for more papers by this author
    • Dr Mallmin serves as a consultant for and is on the advisory board of Novartis. Dr Orwoll serves as a consultant for Merck, Eli Lilly & Co, and Servier and has research support from Amgen, Pfizer, Eli Lilly & Co, Novartis, Zelos Therapeutics, Imaging Therapeutics, and Solvay Pharmaceuticals. All other authors state that they have no conflicts of interest.

  • Anna H Holmberg,

    1. Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, and Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden
    Search for more papers by this author
  • Mattias Lorentzon,

    1. Center for Bone Research at the Sahlgrenska Academy, Departments of Internal Medicine and Geriatrics, University of Gothenburg, Gothenburg, Sweden
    Search for more papers by this author
  • Anders Odén,

    1. Consulting Statistician, Gothenburg, Sweden
    Search for more papers by this author
  • Helena Johansson,

    1. Center for Bone Research at the Sahlgrenska Academy, Departments of Internal Medicine and Geriatrics, University of Gothenburg, Gothenburg, Sweden
    Search for more papers by this author
  • Eric S Orwoll,

    1. Bone and Mineral Unit, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA
    Search for more papers by this author
  • Fernand Labrie,

    1. Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center and Laval University, Québec, Canada
    Search for more papers by this author
  • Magnus K Karlsson,

    1. Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, and Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden
    Search for more papers by this author
  • Östen Ljunggren,

    1. Department of Medical Sciences, University of Uppsala, Uppsala, Sweden
    Search for more papers by this author
  • Claes Ohlsson

    Corresponding author
    1. Center for Bone Research at the Sahlgrenska Academy, Departments of Internal Medicine and Geriatrics, University of Gothenburg, Gothenburg, Sweden
    • Address reprint requests to: Claes Ohlsson, MD, PhD, Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-41345 Göteborg, Sweden
    Search for more papers by this author

Abstract

Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22–1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28–1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16–1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21–1.44) were all inversely, whereas sex hormone–binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22–1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36–1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23–1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18–1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.

Ancillary