title: The Limited Clinical Utility of Testosterone, Estradiol, and Sex Hormone Binding Globulin Measurements in the Prediction of Fracture Risk and Bone Loss in Older Men.
abstract: Measurement of serum testosterone (T) levels is recommended in the evaluation of osteoporosis in older men and estradiol (E2) and sex hormone binding globulin (SHBG) levels are associated with the rate of bone loss and fractures, but the clinical utility of sex steroid and SHBG measurements for the evaluation of osteoporosis in men has not been examined. To evaluate whether measurements of T, E2, and/or SHBG are useful for the prediction of fracture risk or the rate of bone loss in older men, we analyzed longitudinal data from 5487 community-based men participating in the Osteoporotic Fractures in Men (MrOS) study in the United States, Sweden, and Hong Kong. Serum T, E2, and SHBG levels were assessed at baseline; incident fractures were self-reported at 4-month intervals with radiographic verification (US), or ascertained via national health records (Sweden, Hong Kong). Rate of bone loss was assessed by serial measures of hip bone mineral density (BMD). We used receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to assess improvement in prediction. Mean age at baseline was 72 to 75 years and the prevalence of low T levels (<300 ng/dL) was 7.6% to 21.3% in the three cohorts. There were 619 incident major osteoporotic and 266 hip fractures during follow-up of approximately 10 years. Based on ROC curves, there were no improvements in fracture risk discrimination for any biochemical measure when added to models, including the Fracture Risk Assessment Tool (FRAX) with BMD. Although minor improvements in NRI were observed for the dichotomous parameters low bioavailable E2 (BioE2) (<11.4 pg/mL) and high SHBG (>59.1 nM), neither sex steroids nor SHBG provided clinically useful improvement in fracture risk discrimination. Similarly, they did not contribute to the prediction of BMD change. In conclusion, there is limited clinical utility of serum E2, T, and SHBG measures for the evaluation of osteoporosis risk in elderly men. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition, Bone and Mineral Unit, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orwoll
authors.affiliation: Department of Public Health and Preventive Medicine, Division of Biostatistics, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: Lapidus
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition, Bone and Mineral Unit, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Patty Y
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vandenput
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hoffman
authors.affiliation: Geriatric Research Education & Clinical Center, VA Medical Center, Minneapolis, MN, USA.|Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fink
authors.affiliation: Division of Epidemiology, Department of Family Medicine and Public Health, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Gail A
authors.initials: GA
authors.lastname: Laughlin
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: Östen
authors.initials: Ö
authors.lastname: Ljunggren
authors.affiliation: Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of 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, Malmö, Sweden.|Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden.
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Karlsson
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Mellström
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong.|Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kwok
authors.affiliation: Division of Endocrinology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.affiliation: Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kwok
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000368:Aged; D001862:Bone Resorption / Q000097:blood / Q000175:diagnosis*; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood*; D050723:Fractures, Bone / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D006620:Hip Fractures / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D008297:Male; D012372:ROC Curve; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol
keywords: AGING; DXA; EPIDEMIOLOGY; FRACTURE RISK ASSESSMENT; OSTEOPOROSIS