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

Eric S. Orwoll, Jodi Lapidus, Patty Y. Wang, Liesbeth Vandenput, Andrew Hoffman, Howard A. Fink, Gail A. Laughlin, Maria Nethander, Östen Ljunggren, Andreas Kindmark, Mattias Lorentzon, Magnus K. Karlsson, Dan Mellström, Anthony Kwok, Sundeep Khosla, Timothy Kwok, Claes Ohlsson

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (<300ng/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) (<11.4pg/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.

Original languageEnglish (US)
JournalJournal of Bone and Mineral Research
DOIs
StateAccepted/In press - 2016

Fingerprint

Sex Hormone-Binding Globulin
Bone Fractures
Testosterone
Estradiol
Osteoporosis
Hong Kong
Sweden
Bone Density
Serum
Steroids
Pelvic Bones
Bone and Bones
Osteoporotic Fractures
ROC Curve
Health

Keywords

  • AGING
  • DXA
  • EPIDEMIOLOGY
  • FRACTURE RISK ASSESSMENT
  • OSTEOPOROSIS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

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. / Orwoll, Eric S.; Lapidus, Jodi; Wang, Patty Y.; Vandenput, Liesbeth; Hoffman, Andrew; Fink, Howard A.; Laughlin, Gail A.; Nethander, Maria; Ljunggren, Östen; Kindmark, Andreas; Lorentzon, Mattias; Karlsson, Magnus K.; Mellström, Dan; Kwok, Anthony; Khosla, Sundeep; Kwok, Timothy; Ohlsson, Claes.

In: Journal of Bone and Mineral Research, 2016.

Research output: Contribution to journalArticle

Orwoll, ES, Lapidus, J, Wang, PY, Vandenput, L, Hoffman, A, Fink, HA, Laughlin, GA, Nethander, M, Ljunggren, Ö, Kindmark, A, Lorentzon, M, Karlsson, MK, Mellström, D, Kwok, A, Khosla, S, Kwok, T & Ohlsson, C 2016, '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', Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.3021
Orwoll, Eric S. ; Lapidus, Jodi ; Wang, Patty Y. ; Vandenput, Liesbeth ; Hoffman, Andrew ; Fink, Howard A. ; Laughlin, Gail A. ; Nethander, Maria ; Ljunggren, Östen ; Kindmark, Andreas ; Lorentzon, Mattias ; Karlsson, Magnus K. ; Mellström, Dan ; Kwok, Anthony ; Khosla, Sundeep ; Kwok, Timothy ; Ohlsson, Claes. / 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. In: Journal of Bone and Mineral Research. 2016.
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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 (<300ng/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) (<11.4pg/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.",
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AU - Wang, Patty Y.

AU - Vandenput, Liesbeth

AU - Hoffman, Andrew

AU - Fink, Howard A.

AU - Laughlin, Gail A.

AU - Nethander, Maria

AU - Ljunggren, Östen

AU - Kindmark, Andreas

AU - Lorentzon, Mattias

AU - Karlsson, Magnus K.

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N2 - 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 (<300ng/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) (<11.4pg/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.

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