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      Relationship of sex steroid hormones with bone mineral density of the lumbar spine in adult men

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      , MD 1 , , ScD, MPH 2 , , MD 3 , , PhD 4 , , Prof. Dr. oec. troph., MPH 5 ,
      Bone & Joint Research
      Osteopenia, Sex hormones, NHANES

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          Abstract

          Aims

          To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA.

          Methods

          Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity.

          Results

          Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity.

          Conclusion

          In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers.

          Cite this article: Bone Joint Res. 2020;9(3):139–145.

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          Most cited references33

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          Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group.

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            Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen.

            Estrogen (E) deficiency associated with the menopause is the major cause of bone loss in aging women. However, men also lose significant amounts of bone with age, but they do not have the equivalent of menopause, and serum total testosterone (T) and E levels decline only marginally with age in men. Thus, it has been difficult to attribute bone loss in aging men to either T or E deficiency. Here, we show in a population-based, age-stratified sample of 346 men, aged 23-90 yr, that serum total T and E (estradiol plus estrone) levels decreased over the life span by 30% and 12%, respectively, but bioavailable (or nonsex hormone-binding globulin-bound) T and E levels decreased by 64% and 47%, respectively. In these men and in a parallel cohort of 304 women, aged 21-94 yr, serum PTH increased 84% and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx) excretion, a bone resorption marker, increased 77% and 80% between age 50-85 yr in the men and women, respectively. By univariate analyses, serum bioavailable T and E levels correlated positively with bone mineral density (BMD) at the total body, spine, proximal femur, and distal radius and negatively with urinary NTx excretion in men and women. Urinary NTx excretion was also negatively associated with BMD in both sexes. By multivariate analyses, however, serum bioavailable E level was the consistent independent predictor of BMD in both men and postmenopausal women. Thus, bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women. These studies suggest that in contrast to traditional belief, age-related bone loss may be the result of E deficiency not just in postmenopausal women, but also in men.
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              Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.

              The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
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                Author and article information

                Contributors
                Role: Resident Physician
                Role: Professor and Martin D. Abeloff, MD Scholar in Cancer Prevention
                Role: Associate Professor of Oncology and Urology
                Role: Senior Investigator
                Role: Head of the Cancer Registry of the Cantons Zurich and Zug
                Journal
                Bone Joint Res
                Bone & Joint Research
                2046-3758
                March 2020
                16 May 2020
                : 9
                : 3
                : 139-145
                Affiliations
                [1 ]Department of Orthopaedic Surgery, Cantonal Hospital of Baselland, Liestal, Switzerland
                [2 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; James Buchanan Brady Urological Institute, and Department of Urology, Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
                [3 ]Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
                [4 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
                [5 ]Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
                Author notes
                [*]S. Rohrmann; email: sabine.rohrmann@ 123456uzh.ch
                Article
                10.1302_2046-3758.93.BJR-2019-0141.R1
                10.1302/2046-3758.93.BJR-2019-0141.R1
                7229310
                0a0e9742-cd78-4067-be21-aadec563bc0b
                © 2020 Author(s) et al

                Open Access This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                Categories
                Biomaterials
                9
                Osteopenia
                Sex Hormones
                Nhanes

                osteopenia,sex hormones,nhanes
                osteopenia, sex hormones, nhanes

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