Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men.
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ABSTRACT:
SUBMITTER: Beukhof CM
PROVIDER: S-EPMC4824523 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Mutations in the chloride channel 7 gene (CLCN7) cause osteopetrosis, and polymorphisms of CLCN7 in the non-disease allele are associated with penetrance of the autosomal dominant osteopetrosis (ADO) phenotype. Studies have also shown an association between CLCN7 polymorphisms and bone mineral density (BMD) in women. However, there is no study to date that has examined whether CLCN7 polymorphisms underlie normal variation of peak BMD in healthy premenopausal white women and in white men.Six single nucleotide polymorphisms (SNPs) and one variable number tandem repeat (VNTR) polymorphism in the CLCN7 gene were genotyped. Association was tested between CLCN7 gene polymorphisms and both lumbar spine and femoral neck BMD. Healthy premenopausal white sisters (age 33.1+/-7.2, n=1692) and healthy white brothers (age 33.6+/-10.9, n=715) were studied.No significant association between CLCN7 gene polymorphisms and BMD at the lumbar spine or femoral neck was found in white women or white men.Genetic variation in the CLCN7 gene is not a major contributor to the variability in peak BMD at the femoral neck and lumber spine in healthy premenopausal white women and in white men.
| S-EPMC2657035 | biostudies-literature
Project description:BackgroundSevere gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.MethodsOne hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.ResultsAs testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.ConclusionsEstrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.Trial registrationClinicalTrials.gov, NCT00114114.FundingAbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.
| S-EPMC4767351 | biostudies-literature
Project description:Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor ? gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p?=?0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p?=?0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p?=?0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p?=?0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.
| S-EPMC3131390 | biostudies-literature
Project description:UnlabelledThere is a paucity of normative bone mineral density (BMD) data in healthy African women. Baseline total hip and lumbar spine BMD was measured in premenopausal women. BMD distribution was comparable to that of a reference population and was impacted by several factors including contraception and duration of lactation.IntroductionNormative data on bone mineral density (BMD) and the cumulative impact of lactation, contraceptive use, and other factors on BMD in healthy African women have not been well studied.ObjectivesThe objective of this study was to determine the factors associated with BMD in healthy premenopausal women in Uganda and Zimbabwe.MethodsBaseline total hip (TH) and lumbar spine (LS) BMD was measured by dual x-ray absorptiometry in 518 healthy, premenopausal black women enrolling in VOICE, an HIV-1 chemoprevention trial, at sites in Uganda and Zimbabwe. Contraceptive and lactation histories, physical activity assessment, calcium intake, and serum vitamin D levels were assessed. Independent factors associated with BMD were identified using an analysis of covariance model.ResultsThe study enrolled 331 women from Zimbabwe and 187 women from Uganda. Median age was 29 years (IQR 25, 32) and median body mass index (BMI) was 24.8 kg/m(2) (IQR 22.2, 28.6). In univariate analyses, lower TH BMD values were associated with residence in Uganda (p < 0.001), lower BMI (p < 0.001), and any use of and duration of depot-medroxyprogresterone acetate. Use of oral contraceptives, progestin-only implants, and higher physical activity levels were protective against reduced BMD. Similarly, lower LS BMD values were associated with these same factors but also higher parity and history of breastfeeding. In a multivariable analysis, lower TH and LS BMD values were associated with enrollment in Uganda, lower BMI, and lower physical activity level; contraceptive use was associated with lower spine BMD, and breastfeeding contributed to lower total hip BMD.ConclusionsAmong healthy premenopausal women, TH and LS BMD was higher in Zimbabwe than Uganda. Additional factors independently associated with BMD included BMI, physical activity level, contraceptive use, and lactation.
| S-EPMC4564062 | biostudies-literature
Project description:Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 (p = 6.42 × 10(-7)), rs34594869 (p = 6.53 × 10(-7)) and rs17124504 (p = 6.53 × 10(-7)) in 14q31.3 and rs140155614 (p = 8.64 × 10(-7)) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 (p = 6.35 × 10(-7)) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.
| S-EPMC4951402 | biostudies-literature
Project description:Background:Disrupted rest-activity circadian rhythm (RAR) patterns have been associated with poor health outcomes (i.e. diminished cognitive function, increased risk of dementia and falls). Circadian time cues in bone influence the differentiation of osteoblasts and osteoclasts, and bone turnover markers exhibit circadian variation; relationships between bone outcomes and RAR are emerging areas of research. We evaluated associations between RAR and areal bone mineral density (aBMD) at the total hip and femoral neck in older men from the Osteoporotic Fractures in Men (MrOS) cohort. We hypothesized that weaker RAR patterns would be associated with lower aBMD. Methods:MrOS is an ongoing prospective cohort study following ambulatory men ? 65 years (n = 5994) at 6 U.S. clinics (baseline enrollment 3/2000-4/2002); participants for this analysis are from an ancillary study, Outcomes of Sleep Disorders in Older Men (MrOS Sleep). We included data from men who had technically adequate measures of RAR and aBMD at Sleep Visit 1 (12/2003-3/2005), with repeat aBMD at core Visit 3 (3/2007-3/2009) (n = 2412; mean age at Sleep Visit 1: 75.7 ± 5.2 years). aBMD was measured by dual energy x-ray absorptiometry (DXA). Actigraphs worn on the non-dominant wrist were used to collect circadian activity data over 4.8 ± 0.8 consecutive 24-hour periods. An extension of the traditional cosine curve was used to fit RAR to the activity data [Ancoli-Israel et al., 2003; Marler et al., 2006]. Six RAR parameters were evaluated: acrophase (time of peak activity), amplitude (rhythm strength), mesor (mean of activity fitted curve), pseudo F-statistic (overall circadian rhythmicity of rest and activity), alpha statistic (daytime to nighttime activity ratio), and beta statistic (daytime activity). Associations between RAR and aBMD (Sleep Visit 1), and RAR and ?aBMD (Sleep Visit 1-Visit 3) were assessed with generalized linear models. Covariates included age, clinic site, physical activity, race, comorbidity, body mass index (BMI), smoking, alcohol, caffeine, beta blocker use, serum 25(OH) vitamin D and urinary melatonin and calcium. Results:Pseudo F-statistic was significantly associated with total hip aBMD (p-trend = 0.009), femoral neck aBMD (p-trend = 0.007) and total hip ?aBMD (p-trend = 0.017) in minimally adjusted models but not after multivariate (MV) adjustment. Alpha statistic was significantly associated with femoral neck aBMD (p-trend = 0.029) and femoral neck ?aBMD (p-trend = 0.019) in minimally adjusted models; significance was retained in the femoral neck ?aBMD model (p-trend = 0.034) after MV adjustment. There were no consistent, significant associations between the other RAR variables and aBMD or ?aBMD. Conclusions:The data demonstrate modest associations between overall circadian rhythmicity of rest and activity (measured by pseudo F-statistic), as well as daytime to nighttime activity ratio (measured by alpha statistic), aBMD and ?aBMD, but adjustment for covariates related to lifestyle, BMI and comorbidities attenuated most of these associations. These results suggest that RAR patterns are not independently associated with aBMD or four-year ?aBMD at the total hip or femoral neck in older men, but additional research is needed.
| S-EPMC5695538 | biostudies-literature
Project description:Background and objectivesExperimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old.MethodsIn N = 1365 Hortega Study participants >20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure.ResultsThe median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 μg/g creatinine, and 84.9 μg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < -1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 μg/L, which became increasingly positive above ~105 μg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of Se with the incidence of osteoporosis-related bone fractures, the positive association above ~105 μg/L was markedly stronger, compared to the cross-sectional analysis.ConclusionsOur results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.
| S-EPMC9019194 | biostudies-literature
Project description:BackgroundOsteoporosis, characterized by reduced bone mineral density (BMD) increases the risk of all-cause mortality. Assessments of whether dietary selenium intake is related to bone health are scarce, with few relevant studies limited by a small sample size. The aim of the present study was to investigate the association between dietary selenium intake and BMD levels in the National Health and Nutrition Examination Survey (NHANES) database.MethodsWe extracted and aggregated data from 4 cycles of the NHANES [2005-2010, 2013-2014]. Dietary selenium intake was obtained from 24-hour dietary recall interviews. BMD measurement, including the femur, femur neck, trochanter and intertrochanter of the femur, and lumbar spine, was performed using dual-energy X-ray absorptiometry. The multivariable linear regression model for the association between dietary selenium intake and BMD and the generalized additive model (GAM) for the dose-response relationship were used.ResultsA total of 21,939 participants were included. The mean age was 40.68±22.42 years, and 51.28% were male. In the multivariable adjustment model, participants with the highest quintiles of dietary selenium intake (Q5) were associated with increased BMD levels in the total femur (β=0.014, 95% CI: 0.008-0.020, P<0.001), femur neck (β=0.010, 95% CI: 0.004-0.016, P=0.001), trochanter (β=0.011, 95% CI: 0.005-0.017, P<0.001), intertrochanter (β=0.017, 95% CI: 0.010-0.025, P<0.001), and lumbar spine (β=0.013, 95% CI: 0.005-0.020, P<0.001) compared with those in quintile 1 (Q1). The dose-response relationship showed an inverted U-shape relationship between dietary selenium intake and BMD levels (P for nonlinearity <0.05). Participants tended to have increased levels of BMD as the dietary selenium intake increased when dietary selenium was below the turning point, and then a negative relationship was observed when dietary intake was higher than the turning point.ConclusionsOur study indicated that dietary selenium intake exhibited an inverted U-shape trend in relation to BMD levels, which demonstrates the need for selenium status in the body to be considered when discussing the role of dietary selenium intake in BMD. Future studies are needed to confirm these findings and explore the underlying biological mechanism.
| S-EPMC9469114 | biostudies-literature
Project description:IntroductionLow levels of sex hormones are common in patients with chronic kidney disease (CKD) and may be a contributing factor to bone fragility. We investigated associations between levels of sex hormones and bone mineral density (BMD) in adult kidney transplantation candidates.MethodsVolumetric BMD of spine and hip were measured by computed tomography. Parathyroid hormone (PTH), testosterone (T), estradiol (E), and sex hormone-binding globulin were measured from fasting morning blood samples. Bioavailable (Bio) T and E were calculated based on constants for protein binding.ResultsA total of 146 patients (102 men and 44 women) were included in the analyses. The median age was 54 years (range, 32-72 years); 32% were diabetic; and 36% received maintenance dialysis therapy. In men, Bio T was positively associated with BMD at the lumbar spine (β = 5.02, P = 0.002), total hip (β = 6.35, P = 0.001), and femoral neck (β = 13.9, P = 0.002), independently of age, body mass index, dialysis, diabetes type 1 and 2, parathyroid hormone, and steroid exposure. Bio E was positively associated with BMD at the lumbar spine (β = 0.23, P = 0.03) and femoral neck (β = 0.61, P = 0.04) using the same fully adjusted model. In postmenopausal women, Bio T was positively correlated with lumbar spine BMD (r = 0.46, P = 0.02).ConclusionHigh endogenous levels of sex hormones are associated with greater BMD in male kidney transplantation candidates. Disturbances in the gonadal axis may contribute to skeletal fragility in men with late-stage CKD.
| S-EPMC5976823 | biostudies-literature
Project description:BackgroundPuberty is a developmental stage of increased insulin resistance that also is a critical period for bone mass accrual. Historically, African Americans (AA) have lesser risk for osteoporotic fractures compared to European Americans (EA). AA also have higher incidence of insulin resistance. The possibility that bone health and insulin secretion or concentrations are linked has not been investigated.AimsWe aimed to examine the associations of bone mineral density (BMD) and bone mineral apparent density (BMAD) with insulin sensitivity and secretion in healthy adolescent girls and healthy female adults and to evaluate ethnic differences in these associations.Study designObservational cohort design.Place and duration of the studyUniversity of Alabama at Birmingham, between January 2010 and September 2011.MethodologyHealthy, female, non-smoking adolescents and young adults (14-55 years) were enrolled in this observational cohort study.ResultsAdolescents had significantly higher fasting insulin (P=0.0002), insulin area under the curve [AUC] (P= 0.0004) and lower insulin sensitivity (P=0.0005) compared to adults. Among adolescents, AA race was significantly associated with BMD (β=0.086, P=0.01) and BMAD (β=0.0075, P=0.002); however, adjusting for insulin AUC explained this difference. Insulin AUC (β=0.0006, P=0.029) and fasting insulin (β=0.0005, P=0.01) were positively associated with BMAD only in AA adolescents. Insulin AUC and fasting insulin were not significant predictors of BMD for adults.ConclusionThe higher insulin concentration among AA adolescents is associated with increased BMD and higher BMAD.
| S-EPMC4172283 | biostudies-literature