***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: The association between sex hormones and sex hormone binding globin ( SHBG ) with  vertebral fractures in men is not well studied . In these analyses , we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospect i ve cohort study of community dwelling older men . We included data from participants in MrOS who had been r and omly selected for hormone measurement ( N=1463 , including 1054 with follow-up data 4.6years later ) . Major outcomes included prevalent vertebral fracture ( semi-quantitative grade ≥2 , N=140 , 9.6 % ) and new or worsening vertebral fracture ( change in SQ grade ≥1 , N=55 , 5.2 % ) . Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors , including age , bone mineral density , and other sex hormones . Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures ( OR : 1.38 per SD increase , 95 % CI : 1.11 , 1.72 ) . Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures ( OR per SD decrease : 0.86 , 95 % CI : 0.68 to 1.10 ) . Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values ( OR : 1.46 , 95 % CI : 0.99 , 2.16 ) . There was no association between total testosterone and prevalent fracture . In longitudinal analyses , SHBG ( OR : 1.42 per SD increase , 95 % CI : 1.03 , 1.95 ) was associated with new or worsening vertebral fracture , but there was no association with total estradiol or total testosterone . In conclusion , higher SHBG ( but not testosterone or estradiol ) is an independent risk factor for vertebral fractures in older men Context We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity . Design and Setting We performed a nested case-control study within the prospect i ve Women 's Health Initiative Observational Study . Incident nonspine fractures were identified in 381 black , 192 Hispanic , 112 Asian , and 46 Native American women over an average of 8.6 years . A r and om sample of 400 white women who experienced an incident fracture was chosen . One control was selected per case and matched on age , race/ethnicity , and blood draw date .  Bioavailable estradiol ( BioE2 ) , bioavailable testosterone ( BioT ) , and sex hormone-binding globulin ( SHBG ) were measured using baseline fasting serum . Conditional logistic regression models calculated the odds ratio ( OR ) and 95 % confidence interval ( CI ) of fracture across tertiles of hormone . Results In multivariable and race/ethnicity-adjusted models , higher BioE2 ( > 8.25 pg/mL ) and higher BioT ( > 13.3 ng/dL ) were associated with decreased risk of fracture ( OR , 0.65 ; 95 % CI , 0.50 to 0.85 ; P trend = 0.001 and OR , 0.76 ; 95 % CI , 0.60 to 0.96 ; P trend = 0.02 , respectively ) . The interaction term between race/ethnicity and either BioE2 or BioT was not significant . There was no association between SHBG and fracture risk . In models stratifying by race/ethnicity , higher BioE2 was associated with a lower risk of fracture in both white women ( OR , 0.56 ; 95 % CI , 0.36 to 0.87 ) and black women ( OR , 0.61 ; 95 % CI , 0.39 to 0.96 ) . Higher BioT was associated with a significantly lower fracture risk in only black women ( OR , 0.65 ; 95 % CI , 0.43 to 1.00 ) , P trend = 0.03 . Conclusions Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture Sex steroids have an important role in bone health , however previous studies on fracture risk have been carried out in older population s. The EPIC-Oxford study is a prospect i ve cohort of men and women living in the UK . Five years after recruitment , participants self-reported previous fractures .  Sex steroid concentrations ( plasma estradiol , testosterone and sex hormone binding globulin )  were measured in 436 cases ( 155 men , 46 premenopausal women and 235 postmenopausal women ) with an incident fracture and 868 matched controls .  Fracture risk was inversely related to concentrations of estradiol among men ( RR for a doubling of estradiol 0.35 , 95 % CI 0.44–0.96 ) but there was no association between fracture risk and testosterone levels . There were no clear associations between fracture risk and hormone levels among postmenopausal women , however there was suggestion of an inverse association for both estradiol and testosterone as the RR in the highest compared with the lowest tertile for estradiol was 0.74 ( 95 % CI 0.46 , 1.18 ) and testosterone was 0.75 ( 95 % CI 0.49 , 1.16 ) . Among premenopausal women fracture risk was inversely associated with levels of testosterone ( RR for doubling of testosterone 0.46 , 95 % CI 0.26–0.81 ) , with no association between estradiol and fracture risk . SHBG was not associated with risk of fracture among either men or women . In summary , this study finds evidence of an inverse association between endogenous estradiol and risk of fracture in men , and between endogenous testosterone and risk of fracture in premenopausal women but no clear associations among postmenopausal women CONTEXT The relationship between sex steroids and fracture is poorly understood . OBJECTIVE The objective of the study was to examine associations between nonvertebral fracture risk and bioavailable estradiol ( bioE2 ) , bioavailable testosterone ( bioT ) , and SHBG .  DESIGN This was a case-cohort study . SETTING The Osteoporotic Fractures in Men Study ( MrOS ) was conducted in a prospect i ve U.S. cohort in 5995 community-dwelling men 65 yr old or older . PARTICIPANTS Participants included a subcohort of 1436 r and omly chosen white men plus all 446 minorities and all those with incident hip and other nonvertebral fractures . MAIN OUTCOME MEASURES Baseline testosterone and estradiol were measured by mass spectrometry ( MS ) and SHBG by RIA . RESULTS Men with the lowest bioE2 ( < 11.4 pg/ml ) or highest SHBG ( > 59.1 nm ) had greater risk of all nonvertebral fractures [ adjusted hazard ratio ( HR ) [ 95 % confidence interval ] : 1.5 ( 1.2 - 1.9 ) and 1.4 ( 1.1 - 21.8 ) , respectively ] . Men with the lowest bioT ( < 163.5 ng/dl ) had no increased fracture risk after adjustment for bioE2 [ adjusted HR 1.16 ( 0.90 - 1.49 ) ] . A significant interaction between SHBG and bioT ( P = 0.03 ) result ed in men with low bioT and high SHBG having higher fracture risk [ HR 2.1 ( 1.4 - 3.2 ) ] . Men with low bioE2 , low bioT , and high SHBG were at highest risk [ HR 3.4 ( 2.2 - 5.3 ) ] . CONCLUSIONS Older men with low bioE2 or high SHBG levels are at increased risk of nonvertebral fracture . When SHBG levels are high , men with low bioT levels have higher risk . The strongest association occurred when all measures were considered in combination OBJECTIVE Little is known about the association between free IGF-I levels and bone mineral density ( BMD ) . DESIGN A cross-sectional study of 218 healthy subjects ( 103 men , 115 women , age 55 - 80 years ) was carried out . METHODS Fasting serum free IGF-I , total IGF-I , estradiol and sex hormone-binding globulin ( SHBG ) levels were measured . The ratio of estradiol to SHBG was used as an index of free estradiol .  BMD measurements were performed by dual-energy X-ray absorptiometry of the lumbar spine and the proximal femur . RESULTS In multivariate analyses with BMD of the lumbar spine as the dependent variable and serum free IGF-I , age , body mass index ( BMI ) and the free estradiol index as independent variables , the free IGF-I was positively related to the BMD of the lumbar spine in men ( P = 0.02 ) but not in women . When the same analyses for the lumbar BMD were performed with total serum IGF-I the association was also only statistically significant in men ( P = 0.05 ) . In multivariate analyses with the trochanter BMD as the dependent variable and serum free IGF-I , total IGF-I , age , BMI and the free estradiol index as independent variables , the associations between ( free and total ) IGF-I and the trochanter BMD in men was of borderline significance . CONCLUSIONS In elderly men free and total IGF-I were positively related to lumbar BMD , while ( free and total ) IGF-I was borderline positively related to trochanter BMD . As these relationships were not observed in elderly women , we suggest a weak gender-specific anabolic effect of IGF-I on BMD on trabecular bone The serum concentration of sex hormone-binding globulin ( SHBG ) is inversely related to weight and in animal studies is inversely related to protein intake . As SHBG can affect the biological activity of testosterone and estradiol , we wished to determine the role of protein intake on SHBG levels in men . Using data from the Massachusetts Male Aging Study we examined cross-sectional relationships between dietary components and SHBG levels in 1552 men ( aged 40 - 70 yr ) for whom these factors were known . Analyzed by multiple regression , controlling for testosterone and estradiol levels , age ( P<0.001 ) and fiber intake ( P = 0.02 ) were positively correlated to SHBG concentration , whereas body mass index ( P<0.001 ) and protein intake ( P<0.03 ) were negatively correlated to SHBG concentration . The intakes of calories , fat ( animal or vegetable ) , and carbohydrate were not related to SHBG concentration . We conclude that age and body mass index are major determinants of SHBG concentrations in older men , and fiber and protein intake are also significant contributors to SHBG levels , but total caloric intake and the intake of carbohydrate or fat are not significant . Thus , diets low in protein in elderly men may lead to elevated SHBG levels and decreased testosterone bioactivity . The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass , and contribute to the loss of bone density ABSTRACT Previous prospect i ve cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin ( SHBG ) associate with nonvertebral fracture risk in men . The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is , however , less studied . Elderly men ( aged ≥65 years ) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men ( MrOS ) study had baseline estradiol and testosterone analyzed by gas chromatography – mass spectrometry ( GC‐MS ) and SHBG by immunoradiometric assay ( IRMA ) . Incident clinical vertebral fractures  ( n = 242 cases ) were evaluated in 4324 men during an average follow‐up of 9.1 years . In a sub sample of these men ( n = 2256 ) , spine X‐rays  were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures ( n = 157 cases ) . The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models , respectively . Neither serum estradiol ( hazard ratio [ HR ] per SD increase = 0.93 , 95 % confidence interval [ CI ] 0.80–1.08 ) nor testosterone ( 1.05 , 0.91–1.21 ) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set . High serum SHBG , however , associated with increased clinical vertebral fracture risk ( 1.24 , 1.12–1.37 ) . This association remained significant after further adjustment for FRAX with or without bone mineral density ( BMD ) . SHBG also associated with increased incident radiographic vertebral fracture risk ( combined data set ; odds ratio [ OR ] per SD increase = 1.23 , 9 
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Conclusions The present meta- analysis suggests that higher SHBG levels predict an increased risk of fracture in older adults .