Total Body Bone Mineral Density Research Articles

Genetic Prediction of Osteoporosis by Anti-Müllerian Hormone Levels and Reproductive Factors in Women: A Mendelian Randomization Study.

Previous observational studies have suggested that anti-Müllerian hormone (AMH) and reproductive factors are linked to reduced bone mineral density (BMD) and an increased risk of osteoporosis (OP) in women. However, related studies are limited, and these traditional observational studies may be subject to residual confounders and reverse causation, while also lacking a more comprehensive observation of various reproductive factors. Univariate and multivariate two-sample Mendelian randomization analyses were conducted to determine the causal associations of AMH levels and six reproductive factors with BMD and OP, using the random-effects inverse-variance weighted method. Heterogeneity was assessed using Cochran's Q-statistic, and sensitivity analyses were performed to identify causal correlations. Age at menarche (AAM) was negatively associated with total body BMD (TB-BMD) in females aged 45-60 and over 60years, as well as with heel bone mineral density (eBMD). Conversely, age at natural menopause (ANM) was positively associated with TB-BMD in the same age ranges and with eBMD. ANM was only causally associated with self-reported OP and showed no significant correlation with definitively diagnosed OP. Neither AMH level nor other reproductive factors were significantly associated with a genetic predisposition to BMD at any age and OP. Later AAM and earlier ANM are significantly genetically causally associated with decreased BMD but not with OP. AMH levels, length of menstrual cycle, age at first birth, age at last birth, and number of live births, in terms of genetic backgrounds, are not causally related to BMD or OP.

Causal relationship between intervertebral disc degeneration and osteoporosis: a bidirectional two-sample Mendelian randomization study.

The relationship between intervertebral disc degeneration (IVDD) and osteoporosis (OP), diagnosed primarily using bone mineral density (BMD), remains unclear so far. The present study, therefore, aimed to investigate the potential relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses. Specifically, the impact of bone mineral density on the development of intervertebral disc degeneration was evaluated. The genome-wide association studies (GWAS) summary data of OP/BMDs and IVDD were collected from the FinnGen consortium, the GEFOS consortium, and MRC-IEU. The relationship between IVDD and OP was then explored using TSMR. The inverse-variance weighted (IVW) method was adopted as the primary effect estimate, and the reliability and stability of the results were validated using various methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. No significant causal relationship was observed between OP and IVDD (IVW, P > 0.05) or between femoral neck BMD (FA-BMD) and IVDD when OP and FA-BMD were used as exposures. However, increased levels of total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were revealed as significant risk factors for IVDD (TB-BMD: IVW, OR = 1.201, 95% CI: 1.123-1.284, P = 8.72 × 10-8; LS-BMD: IVW, OR = 1.179, 95% CI: 1.083-1.284, P = 1.43 × 10-4). Interestingly, both heel BMD (eBMD) and femur neck BMD (FN-BMD) exhibited potential causal relationships (eBMD: IVW, OR = 1.068, 95% CI: 1.008-1.131, P = 0.0248; FN-BMD, IVW, OR = 1.161, 95% CI: 1.041-1.295, P = 0.0074) with the risk of IVDD. The reverse MR analysis revealed no statistically causal impact of IVDD on OP and the level of BMD (P > 0.05). OP and the level of FA-BMD were revealed to have no causal relationship with IVDD. The increased levels of TB-BMD and LS-BMD could promote the occurrence of IVDD. Both eBMD and FN-BMD have potential causal relationships with the risk of IVDD. No significant relationship exists between IVDD and the risk of OP. Further research is warranted to comprehensively comprehend the molecular mechanisms underlying the impact of OP and BMD on IVDD and vice versa.

Causal association of genetically determined caffeine intake from tea or coffee with bone health: a two-sample Mendelian randomization study.

Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata. Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent. In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006-0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654-0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093-0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45-60years, but we lacked evidence of association in other strata. Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk.

Diabetes and osteoporosis: a two-sample mendelian randomization study

BackgroundThe effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design.MethodsA two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches.ResultsThe IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (β = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (β = 0.033, 95% CI: 0.003, 0.062), heel-BMD (β = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (β = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (β ranged from − 0.012 to 0.075).ConclusionsOur results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Assessment of Relative Energy Deficiency in Sport (REDs) Risk among Adolescent Acrobatic Gymnasts.

Energy imbalance exposes athletes to relative energy deficiency in sports (REDs) syndrome. Data on energy consumption, REDs, and bone mineral density (BMD) in adolescent acrobatic gymnasts, especially in males, are scarce. Our aim was to examine the eating habits, energy balance, body composition, and BMD of these athletes. In this study, 18 healthy adolescents participating in competitive acrobatic gymnastics completed a questionnaire, underwent a dual-energy X-ray absorptiometry scan (DXA), received a food log, and had their activities monitored for 3 days. Eighteen acrobats were enrolled (mean age: 14.3 ± 1.2 years; males: 6/18). The mean total body BMD Z-score was 0.4 ± 1.0. Top-position acrobats (7/18) had significantly lower total body BMD Z-scores than base-positioned acrobats (-0.2 ± 0.3 vs. 0.8 ± 0.3, p = 0.032), though their forearms were not significantly different (0.2 ± 0.5 vs. 0.8 ± 0.7, p = 0.331). No sex differences were found for BMD Z-scores, BMI, or energy availability. The BMD parameters of the acrobats were within the normal range for a healthy pediatric population, although three had low BMDs (<-1 SD) for healthy athletes. Total body and LS BMD Z-scores were significantly lower in top-position athletes compared to base-position athletes. These findings suggest personalized (top vs. base) training programs (high-impact training) that may achieve better health outcomes.

Assessing the interaction effects of mitochondrial DNA polymorphisms and lifestyle on heel bone mineral density.

Bone mineral density (BMD) is a major predictor of osteoporotic fractures, and previous studies have reported the effects of mitochondrial dysfunction and lifestyle on BMD, respectively. However, their interaction effects on BMD are still unclear. Therefore, we aimed to investigate the possible interaction of mitochondrial DNA (mtDNA) and common lifestyles contributing to osteoporosis. Our analysis included 119,120 white participants (Nfemale=65,949 and Nmale=53,171) from the UK Biobank with heel BMD phenotype data. A generalized linear regression model of PLINK was performed to assess the interaction effects of mtDNA and five life environmental factors on heel BMD, including smoking, drinking, physical activity, dietary diversity score, and vitamin D. In addition, we also performed linear regression analysis for total body BMD. Finally, we assessed the potential causal relationships between mtDNA copy number (mtDNA-CN) and life environmental factors using Mendelian randomization (MR) analysis. Our study identified four mtDNA loci showing suggestive evidence of heel BMD, such as m.16356T>C (MT-DLOOP; P =1.50×10-3) in total samples. Multiple candidate mtDNA×lifetsyle interactions were also detected for heel BMD, such as MT-ND2×physical activity (P = 2.88×10-3) in total samples and MT-ND1×smoking (P = 8.54×10-4) in males. Notably, MT-CYB was a common candidate mtDNA loci for heel BMD to interact with five life environmental factors. Multivariable MR analysis indicated a causal effect of physical activity on heel BMD when mtDNA-CN was considered (P =1.13×10-3). Our study suggests the candidate interaction between mitochondria and lifestyles on heel BMD, providing novel clues for exploring the pathogenesis of osteoporosis.

Association of coffee intake with bone mineral density: a Mendelian randomization study.

In observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two. Genetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran's Q test, and Leave-one-out test) were used to test the robustness of the results. After Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent. The results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy.

Causal Relationship of Obstructive Sleep Apnea with Bone Mineral Density and the Role of BMI.

Observational studies have yielded conflicting evidence concerning the relationships between obstructive sleep apnea (OSA) and bone mineral density (BMD). As the exact causal inferences remain inconclusive, we conducted a two-sample Mendelian randomization (MR) to identify the causal associations between OSA and BMD. Single-nucleotide polymorphisms associated with OSA were extracted from the FinnGen study. Summary statistics for 10 BMD measured at different age or skeletal sites were obtained from the publicly availableIEU GWAS database. Inverse-variance weighted (IVW) method was chosen as the primary analysis, combined with several sensitivity analyses to evaluate the robustness of results. The study design included two-sample MR and network MR. Our primary MR analysis revealed that genetically predicted OSA was positively linked to increased forearm BMD (β = 0.24, 95% confidence interval [CI]: 0.06-0.41, p = 0.009) and heel BMD (β=0.10, 95% CI = 0.02-0.18, p = 0.018), while no significant causal relationships were observed between OSA and total body BMD, lumbar spine BMD, or femoral neck BMD (all p > 0.05). Network MR suggests that OSA might act as a mediating factor in the effect of BMI on forearm BMD and heel BMD, with a mediated portion estimated at 73% and 84%, respectively. Our findings provide support for a causal relationship between genetically predicted OSA and increased forearm BMD and heel BMD. Furthermore, our results suggest that OSA may play a role in mediating the influence of BMI on BMD.

Tea intake and total body bone mineral density of all ages: a Mendelian randomization analysis.

There is increasing evidence indicating that tea intake affects bone mineral density levels; however, the causality between tea intake and bone mineral density is inconclusive. This study aimed to assess the causal relationship between tea intake and total body bone mineral density (TB-BMD) through two-sample Mendelian randomization (MR) analysis. We conducted a two-sample MR approach to estimate the potential causal effects of tea intake on TB-BMD at all ages in a European population. The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs), identified from a genome-wide association meta-analysis of tea intake (N = up to 447,485 individuals) and from the GEnetic Factors for OSteoporosis (GEFOS) Consortium's genome-wide association meta-analysis (N = up to 56,284 individuals), with baseline data collected in 2018 and populations derived from the European ancestry. The association between each SNP and TB-BMD was weighted by its association with tea intake, and estimates were combined mainly using an inverse-variance weighted meta-analysis. In addition, we explored the potential causal effects between green tea intake, herbal tea intake, and TB-BMD. The MR analysis revealed that genetically determined tea intake exerts a causal impact on TB-BMD, with an odds ratio (OR) of 1.204 (95% CI: 1.062-1.366, p = 0.004), especially in the age group of 45-60 years (OR = 1.360, 95% CI: 1.088-1.700, p = 0.007). No horizontal pleiotropy and heterogeneity were observed. However, there was no causal effect of tea intake on TB-BMD in the age groups of 0-15, 15-30, 30-45, and over 60 years. In the subgroup analysis, when green tea intake was regarded as the exposure factor, no salient associations were found between green tea consumption and TB-BMD (IVW p = 0.368). Similarly, there was also no causal association between herbal tea intake and TB-BMD (IVW p = 0.264). The findings of this study support the evidence that tea consumption increases bone density and reduces the risk of osteoporosis in the age group of 45-60 years within the European population.

Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort.

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305g/cm2 in femur neck BMD, 0.0075-0.0273g/cm2 in femur troch BMD, 0.0173-0.0345g/cm2 in LS BMD, and 0.0141-0.0339g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65yr.

Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study

BackgroundObservational studies have suggested that type 2 Diabetes Mellitus (DM2) is a potentially modifiable risk factor for lower BMD, but the causal relationship is unclear. This study aimed to examine whether the association of DM2 with lower BMD levels was causal by using Mendelian randomization (MR) analyses.MethodsWe collected genome-wide association study data for DM2 and BMD of total body and different skeletal sites from the IEU database. Subsequently, we performed a two-sample Mendelian randomization analysis using the Two Sample MR package.ResultsWe identified a positive association between DM2 risk (61,714 DM2 cases and 596,424 controls) and total BMD, and other skeletal sites BMD, such as femoral neck BMD, ultra-distal forearm BMD and heel BMD. However, non-significant trends were observed for the effects of DM2 on lumbar-spine BMD.ConclusionIn two-sample MR analyses, there was positive causal relationship between DM2 and BMD in both overall samples. In summary, while observational analyses consistently indicate a strong association between DM2 and low BMD, our MR analysis introduces a nuanced perspective. Contrary to the robust association observed in observational studies, our MR analysis suggests a significant link between DM2 and elevated BMD.

Association Between Vertebral Bone Quality Score and Dual-Energy X-ray Absorptiometry for the Assessment of Bone Mineral Density in Adolescent Patients.

The MRI-based vertebral bone quality (VBQ) score is an assessment tool for bone mineral density (BMD) that has been validated in adults against the clinical standard of dual-energy X-ray absorptiometry (DEXA). However, VBQ has yet to be validated against DEXA for use in adolescents. This study evaluated the associations between adolescent VBQscores, DEXA Z-scores, and BMDvalues. The radiographic records of 63 consecutive patients between the ages of 11 and 21 who underwent MRI of the abdomen and pelvis and DEXA of the spine and hip were retrieved. The collected radiographic data consisted of the MRI-based VBQ score, DEXA Z-score, and BMD values of the femoral neck, L1-4 vertebrae, and total body. The VBQ score was calculated by taking the median signal intensity (MSI) from L1-L4 and the SI of the L3 cerebrospinal fluid (CSF). The VBQ score was derived as the quotient of MSIL1-L4 divided by SICSF. A mean VBQ score of 2.41 ± 0.29 was observed. Strong correlations of -0.749 (p<0.0001) and -0.780 (p<0.0001) were detected between the VBQ score and DEXA femoral neck and spine Z-scores, respectively. Correlations between VBQ score and DEXA femoral neck, spine, and total body BMD scores were -0.559 (p<0.0001), -0.611 (p<0.0001), and -0.516 (p<.0001), respectively. No significant correlations were found between the VBQ score and age, BMI, weight, or height. A mean difference in VBQ score of -0.155 (p=0.035) was observed between sexes. VBQ demonstrated moderate predictive ability for DEXA-derived Z-scores and BMD scores. VBQ scores were strongly correlated with DEXA Z-scores and moderately correlated with BMD values. The VBQ score can also be used by adolescent patients as an accessory tool to assess bone health.

Effect of Personality and Physical Activity on Bone Mineral Density in College Students: A Cross-sectional Survey

To explore the correlation between 5 dimensions of personality, physical activity (PA), and bone mineral density (BMD) among college students. A total of 705 undergraduates (329 males and 376 females) from a sports university were recruited. Based on their sports training experience, the participants were divided into 6 major sports groups, including ball sports, skilled sports, competitive sports, track and field, leisure sports, and no sports. Students with professional sports training (ie, athletes) were categorized into ballgame, skilled, competitive, and track and field groups, while the rest (non-athletes) were placed in leisure and no sports groups. Ten-Item Personality Inventory in China (TIPI-C), or the 5-factor model of personality, was used to measure the 5 personality dimensions of openness, conscientiousness, extraversion, agreeableness, and neuroticism of the participants. Their daily level was measured with GT3X+ triaxial accelerometers over 7 continuous days. Then, parameter thresholds were established and the participants' PA was categorized as light (LPA), moderate (MPA), and vigorous (VPA). The bone mineral density (BMD) of arms, legs, and the total body was measured using dual-energy X-ray absorptiometry. The mediation effect of PA and that of the 5-factor model of personality were tested using PROCESS and Sobel tests. The correlation between the 5 personality dimensions, PA, and BMD was explored, with PA and the 5 personality dimensions as mediator variables. A comparison of PA and BMD was conducted across the 6 major sports groups. The correlation between PA of different intensities and BMD was also analyzed using Spearman's correlation. Although there were 90 potential relationships between PA, the 5 personality dimensions, and BMD, only 3 were significant. When conscientiousness was used as an independent variable and MPA, as a mediating variable, statistically significant differences in PROCESS results were reported (P<0.01), with MPA mediating 17.3% of arm BMD, 19.4% of leg BMD, and 19.1% of total body BMD. Among male students, there was no significant difference in LPA among the 6 groups, but significant differences in MPA and VPA (P<0.05). Among female students, significant differences in LPA, MPA, and VPA were observed in all 6 groups and the differences between MPA and VPA were especially prominent (P<0.05). For both males and females, the differences in arm, leg, and total body BMD across the 6 groups were statistically significant (P<0.05), with these differences being more pronounced in females. There was no correlation between LPA and BMD in either sex. MPA and VPA were positively correlated with BMD, with MPA correlating with arm, leg, and total body BMD (males, Spearman's correlation [rs]: 0.11-0.14, P<0.05; females, rs: 0.20-0.23, P<0.01). VPA correlated with arm, leg, and total body BMD (males, rs: 0.11-0.23, P<0.05; females, rs: 0.26-0.30, P<0.01). MPA is associated with BMD in college students scoring high in the conscientiousness dimension of personality. In addition, there is a weak positive correlation between both MPA and VPA and BMD levels, with these associations being more pronounced in females.

Association between fatty liver index and controlled attenuation parameters as markers of metabolic dysfunction-associated fatty liver disease and bone mineral density: observational and two-sample Mendelian randomization studies.

Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.

Comparison of physiological and behavioral nutrition-related factors in people with and without adolescent idiopathic scoliosis, from cohort data at 8 to 20years.

Nutrition-related variables including lower body mass index (BMI), lower bone mineral density (BMD), altered body composition and hormone levels have been reported in adolescent idiopathic scoliosis (AIS). The aims of this study were to determine if physiological and behavioral nutrition-related factors differ between people with and without AIS, and to quantify their relationship with AIS, in unbiased cohort sample. BMI, presence of an eating disorder, leptin, adiponectin, BMD, vitamin D, lean mass, and fat mass were compared between those with and without AIS at ages 8, 10, 14, 17, and 20years, and multiple logistic regression was performed between these variables and AIS. Lower total body BMD (median, 1.0g/cm2 vs 1.1g/cm2; p = .03) and lean mass (median, 38.8kg vs 46.0kg; p = .04) at age 20years were observed in those with AIS compared to those without scoliosis. At age 20, the odds of AIS were 3.23 times higher for adolescents with an eating disorder compared to those with no eating disorder (95% CI, 1.02-8.63) when adjusted for BMI. Every 1kg/m2 increase in BMI decreased the odds of AIS by 0.88 times (95% CI, 0.76-0.98), after adjusting for eating disorder diagnosis. In conclusion, lower BMI in mid-adolescence and presence of eating disorder outcomes, lower BMD, and lower lean mass in late adolescence were associated with the presence of AIS. Current data do not explain the mechanisms for these associations but suggest that serum leptin, adiponectin, and vitamin D are unlikely to be contributing factors. Conclusive determination of the prevalence of eating disorders in AIS will require further studies with larger sample sizes.

Causal Relationships between Air Pollutant Exposure and Bone Mineral Density and the Risk of Bone Fractures: Evidence from a Two-Stage Mendelian Randomization Analysis.

A number of studies from the literature have suggested that exposure to air pollutants is associated with a declined bone mineral density (BMD), and increased risks of osteoporosis (OP) and bone fractures. This study was performed to systemically assess the genetically causal associations of air pollutants with site-/age-specific BMD and risk of bone fractures with the implementation of two-sample Mendelian randomization (TSMR) and multivariate Mendelian randomization (MVMR). The TSMR analysis was implemented to infer the causal associations between air pollutants and BMD and the risk of bone fractures, additional MVMR analysis was used to further estimate the direct causal effects between air pollutants and BMD, the occurrence of OP, and bone fractures. The results showed that NOx exposure contributed to lower femoral neck BMD (FN-BMD) (β = -0.71, 95%CI: -1.22, -0.20, p = 0.006) and total body BMD (TB-BMD) (β = -0.55, 95%CI: -0.90, -0.21, p = 0.002). Additionally, exposure to PM10 was found to be associated with a decreased TB-BMD (B β = -0.42, 95%CI: -0.66, -0.18, p = 0.001), further age-specific subgroup analysis demonstrated the causal effect of PM10 exposure on the decreased TB-BMD in a subgroup aged 45 to 60 years (β = -0.70, 95%CI: -1.12, -0.29, p = 0.001). Moreover, the findings of the MVMR analysis implied that there was a direct causal effect between PM10 exposure and the decreased TB-BMD (45 < age < 60), after adjusting for PM2.5 and PM2.5 -10 exposure. Our study provides additional evidence to support the causal associations of higher concentrations of air pollutant exposure with decreased BMD, especially in those populations aged between 45 to 60 years, suggesting that early intervention measures and public policy should be considered to improve public health awareness and promote bone health.

Lipid Metabolism, Methylation Aberrant, and Osteoporosis: A Multi-omics Study Based on Mendelian Randomization.

Observational studies have shown a causal association between dyslipidemia and osteoporosis, but the genetic causation and complete mechanism of which are uncertain. The disadvantage of previous observational studies is that they are susceptible to confounding factors and bias, that makes it difficult to infer a causal link between those two diseases. Abnormal epigenetic modifications, represented by DNA methylation, are important causes of many diseases. However, there are no studies showing a bridging role for methylation modifications in blood lipid metabolism and osteoporosis. SNPs for lipid profile (Blood VLDL cholesterol (VLDL-C), blood LDL cholesterol (LDL-C), blood HDL cholesterol (HDL-C), blood triglycerides (TG), diagnosed pure hypercholesterolaemia, blood apolipoprotein B (Apo B), blood apolipoprotein A1(Apo A1)), and bone mineral density (BMD) in different body parts (Heel BMD, lumbar BMD, whole-body BMD, femoral neck BMD) were obtained from large meta-analyses of genome-wide association studies as instrumental variables for two-sample Mendelian randomization. Assessment of the genetic effects of lipid profile-associated methylation sites and bone mineral density was carried out using the summary-data-based Mendelian randomization (SMR) method. Two-sample Mendelian randomization showed that there was a negative causal association between hypercholesterolaemia and heel BMD (p = 0.0103, OR = 0.4590), and total body BMD (p = 0.0002, OR = 0.2826). LDL-C had a negative causal association with heel BMD (p = 8.68E-05, OR = 0.9586). VLDL-C had a negative causal association with heel BMD (p = 0.035, OR = 0.9484), lumbar BMD (p = 0.0316, OR = 0.9356), and total body BMD (p = 0.0035, OR = 0.9484). HDL-C had a negative causal association with heel BMD (p = 1.25E-05, OR = 0.9548), lumbar BMD (p = 0.0129, OR = 0.9358), and total body BMD (p = 0.0399, OR = 0.9644). Apo B had a negative causal association with heel BMD (p = 0.0001, OR = 0.9647). Apo A1 had a negative causal association with heel BMD (p = 0.0132, OR = 0.9746) and lumbar BMD (p = 0.0058, OR = 0.9261). The p-values of all positive results corrected by the FDR method remained significant and sensitivity analysis showed that there was no horizontal pleiotropy in the results despite the heterogeneity in some results. SMR identified 3 methylation sites associated with lipid profiles in the presence of genetic effects on BMD: cg15707428(GREB1), cg16000331(SREBF2), cg14364472(NOTCH1). Our study provides insights into the potential causal links and co-pathogenesis between dyslipidemia and osteoporosis. The genetic effects of dyslipidaemia on osteoporosis may be related to certain aberrant methylation genetic modifications.

The association of bone mineral density and dementia: the Rotterdam Study

AbstractBackgroundLow bone mineral density and dementia commonly co‐occur in the elderly, with bone loss accelerating in dementia patients due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists prior to the onset of dementia. Therefore, we investigated how dementia risk was affected by bone mineral density at various skeletal regions in community‐dwelling older adults.MethodIn a prospective population‐based cohort study, bone mineral density at the femoral neck, lumbar spine, and total body and the trabecular bone score were obtained using dual‐energy X‐ray absorptiometry (DXA) in 3,651 participants free from dementia between 2002‐2005. Persons at risk of dementia were followed up until 1 January 2020. For analyses of the association between bone mineral density at baseline and the risk of incident dementia, we used Cox proportional‐hazards regression analyses, adjusting for age, sex, educational attainment, physical activity, smoking status, body mass index, systolic blood pressure, diastolic blood pressure, cholesterol level, high‐density lipoprotein cholesterol, history of comorbidities (stroke and diabetes mellitus), and APOE genotype.ResultAmong the 3,651 participants (median age 72.3±10.0 years, 57.9% women), 688 (18.8%) developed incident dementia during a median of 11.1 years, of whom 528 (76.7%) developed Alzheimer’s disease. During the whole follow‐up, participants with lower bone mineral density at the femoral neck (per SD decrease) were more likely to develop all‐cause dementia (Hazard ratio [HR] total follow‐up: 1.12, 95% Confidential interval [CI]: 1.02‐1.23) and Alzheimer’s disease (HR total follow‐up: 1.14, 95% CI: 1.02‐1.28). Within the first ten years following baseline, the risk of dementia was greatest for groups with the lowest tertile of bone mineral density (femoral neck bone mineral density, HR0‐10years 2.03; 95% CI, 1.39–2.96; total body bone mineral density, HR0‐10years 1.42; 95% CI, 1.01‐2.02; trabecular bone score, HR0‐10years 1.59; 95% CI, 1.11‐2.28).ConclusionIn conclusion, participants with low femoral neck and total body bone mineral density and low trabecular bone score were more likely to develop dementia. Further studies should focus on the predictive ability of bone mineral density for dementia.

Diet-derived antioxidants and osteoporosis: A Mendelian randomization study.

Antioxidants can prevent osteoporosis, but the association between serum antioxidants and the cause of osteoporosis remains unknown. We aimed to utilize Mendelian randomization (MR) to determine whether genetically predicted serum levels of diet-derived antioxidants can affect the risk of osteoporosis, to determine the effect of dietary supplementation of antioxidants. Genetic variants associated with diet-derived antioxidants were selected from the genome-wide association studies. A total of 12,946 osteoporosis cases and 506,624 healthy controls were obtained from UK Biobank (UKB) and Genetic Factors of Osteoporosis (GEFOS) consortia. We implemented a two-sample MR design and performed several sensitivity analyses to evaluate the causal relationship. In UKB, the genetically predicted higher β-carotene (OR = 0.863, p = 7.37 × 10-6, power = 100%) and γ-tocopherol (OR = 0.701, p = 0.021, power = 5%) had an inverse relationship with osteoporosis. However, only the association of serum β-carotene passed FDR correction. In GEFOS, there were no significant diet-derived antioxidants. The direction of the association of β-carotene with osteoporosis (OR = 0.844, p = 0.106, power = 87%) was consistent with that in the UKB dataset. A fixed-effects meta-analysis confirmed that β-carotene (OR = 0.862, p = 2.21 × 10-6) and γ-tocopherol (OR = 0.701, p = 2.31 × 10-2) could decrease the risk of osteoporosis. To reduce exclusion limit bias, we used total body bone mineral density, lumbar spine bone mineral density and femoral neck bone mineral density as surrogates and found that the genetically elevated circulating β-carotene level could increase total body BMD (beta = 0.043, p-value = 8.26 x 10-5, power = 100%), lumbar spine BMD (beta = 0.226, p-value = 0.001, power = 100%) and femoral neck BMD(beta = 0.118, p-value = 0.016, power = 100%). We observed that genetically predicted serum β-carotene could elevate BMD and prevent osteoporosis.