title: Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study.
abstract: The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 μg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 μg/mL are at highest risk. © The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Nethander
authors.affiliation: Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
authors.affiliation: Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.
authors.forename: Östen
authors.initials: Ö
authors.lastname: Ljunggren
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Lorentzon
authors.affiliation: Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, and Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
authors.forename: Björn E
authors.initials: BE
authors.lastname: Rosengren
authors.affiliation: Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, and Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Karlsson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Mellström
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vandenput
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D003687:Dehydroepiandrosterone / Q000097:blood*; D050723:Fractures, Bone / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D010024:Osteoporosis / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology
chemical_list: D003687:Dehydroepiandrosterone
keywords: DHEAS; FRACTURE RISK ASSESSMENT; GENERAL POPULATION STUDIES; MEN; SEX STEROIDS