Associations of Sex Hormone-binding Globulin with Bone Mineral Density Among US Adults, NHANES 2013–2016

Yang, Fan; Yang, Dawei; Zhou, Yinan; Wu, Jianjun

doi:10.2147/ijgm.s329992

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…However, increase in SHBG levels were inversely related to TH BMD loss in men but were not associated with BMD loss at any site in women. Yang et al (36) conducted a cross-sectional study of 6,434 participants to examine the association between sex hormone levels and BMD and found a differential effect of SHBG on BMD by sex, which was similar to our findings.…”

Section: Discussionsupporting

confidence: 90%

Sex-specific differences in bone mineral density loss after sleeve gastrectomy

Yang

Ye²,

Tu³

et al. 2022

Front. Med.

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BackgroundSleeve gastrectomy is an effective bariatric procedure; however, sleeve gastrectomy-related adverse skeletal outcomes have been increasingly reported. High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes. The aim of this study was to identify sex-specific changes in BMD following sleeve gastrectomy and to evaluate the role of SHBG in this process.MethodsThis retrospective study included 19 middle-aged men and 30 non-menopausal women with obesity who underwent sleeve gastrectomy in China. Anthropometrics, bone turnover markers, calciotropic hormones, BMD, SHBG, and gonadal steroids were measured preoperatively and at 6 and 12 months postoperatively. Longitudinal changes in BMD, bone turnover markers and SHBG were compared between sexes by linear mixed models. Multiple stepwise regression analysis was used to identify the predictors of BMD loss at the investigated bone sites.ResultsOver the 12-month study period, total hip and femoral neck BMD decreased, while lumbar spine BMD remained largely unchanged in both sexes. Linear mixed models revealed significant sex × time interaction effects in total hip BMD and SHBG, showing that men had a significantly greater reduction in total hip BMD and less increase in SHBG after sleeve gastrectomy than women. In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted β = −0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women (adjusted β = 0.508, P = 0.01) but not men.ConclusionSignificant sex-specific BMD changes were observed after sleeve gastrectomy in the current study. Sleeve gastrectomy-related increase in SHBG may be a specific risk factor for total hip BMD loss in men. Our results indicate that sex-specific screening may be warranted to facilitate personalized postoperative bone care in this population.

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Section: Discussionsupporting

confidence: 90%

Sex-specific differences in bone mineral density loss after sleeve gastrectomy

Yang

Ye²,

Tu³

et al. 2022

Front. Med.

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“…A cross-sectional study of US adults reported that the value of SHBG for predicting bone loss in adults may improve ( 7 ). A previous cross-sectional study of 142 Moroccan men with no prior diagnosis of osteoporosis reported that BMD at the total hip was negatively correlated with SHBG ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

“…Sex hormone-binding globulin (SHBG) is synthesized by the liver and released into the bloodstream, where it regulates the bioavailability of sex hormones by binding to them ( 6 ). Studies have thus far evaluated the association of SHBG with BMD in adults, postmenopausal women, and older adults ( 7 – 9 ). However, the association in adolescent boys and girls remains inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Association of Sex Hormones and Sex Hormone-Binding Globulin Levels With Bone Mineral Density in Adolescents Aged 12–19 Years

Cao

et al. 2022

Front. Endocrinol.

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BackgroundSex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12–19 years.MethodsThe data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.ResultsA total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.ConclusionsWe found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.

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“…Zha et al investigated the correlation between SHBG and testosterone levels in blood and the BMD of hip bones and LS in Chinese men over 45 years of age and found that the SHBG level was negatively correlated with BMD [ 25 ]. In the US population, a cross-sectional study of 6,434 participants aged 18–80 years from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 found that SHBG levels were significantly associated with LS-BMD and that SHBG levels increased the predictive value of bone loss in adults [ 26 ]. In Koreans, SHBG levels were negatively correlated with the BMD of the pelvis but not with the BMD of other regions [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…SHBG levels have been linked to a number of diseases, including osteoporosis [24]. The association between SHBG and bone mineral density has been investigated in several cross-sectional studies in different countries [25][26][27]. Two studies in Chinese and US populations showed an increased risk of osteoporosis with increased SHBG levels.…”

Section: Discussionmentioning

confidence: 99%

Causal relationships between sex hormone traits, lifestyle factors, and osteoporosis in men: A Mendelian randomization study

Wang

Cheng²,

Wei³

et al. 2022

PLoS ONE

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Although observational studies have explored factors that may be associated with osteoporosis, it is not clear whether they are causal. Osteoporosis in men is often underestimated. This study aimed to identify the causal risk factors associated with bone mineral density(BMD) in men. Single nucleotide polymorphisms (SNPs) associated with the exposures at the genome-wide significance (p < 5x10-8) level were obtained from corresponding genome-wide association studies (GWASs) and were utilized as instrumental variables. Summary-level statistical data for BMD were obtained from two large-scale UK Biobank GWASs. A Mendelian randomization (MR) analysis was performed to identify causal risk factors for BMD. Regarding the BMD of the heel bone, the odds of BMD increased per 1-SD increase of free testosterone (FT) (OR = 1.13, P = 9.4 × 10−17), together with estradiol (E2) (OR = 2.51, P = 2.3 × 10−4). The odds of BMD also increased with the lowering of sex-hormone binding globulin (SHBG) (OR = 0.87, P = 7.4 × 10−8) and total testosterone (TT) (OR = 0.96, P = 3.2 × 10−2) levels. Regarding the BMD of the lumbar spine, the odds of BMD increased per 1-SD increase in FT (OR = 1.18, P = 4.0 × 10−3). Regarding the BMD of the forearm bone, the odds of BMD increased with lowering SHBG (OR = 0.75, P = 3.0 × 10−3) and TT (OR = 0.85, P = 3.0 × 10−3) levels. Our MR study corroborated certain causal relationships and provided genetic evidence among sex hormone traits, lifestyle factors and BMD. Furthermore, it is a novel insight that TT was defined as a disadvantage for osteoporosis in male European populations.

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Associations of Sex Hormone-binding Globulin with Bone Mineral Density Among US Adults, NHANES 2013–2016

Cited by 8 publications

References 29 publications

Sex-specific differences in bone mineral density loss after sleeve gastrectomy

Sex-specific differences in bone mineral density loss after sleeve gastrectomy

Association of Sex Hormones and Sex Hormone-Binding Globulin Levels With Bone Mineral Density in Adolescents Aged 12–19 Years

Causal relationships between sex hormone traits, lifestyle factors, and osteoporosis in men: A Mendelian randomization study

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