Forearm Bone Mineral Density Research Articles

Dietary patterns and bone density among school-aged children: a cross-sectional study in China.

Diet is an essential modifiable determinant of bone health, yet the associations between dietary patterns (DPs) and bone mineral density (BMD) in Chinese children remain limited. This study aimed to investigate the relationship between overall diet and low BMD risk among school-aged children in China. A total of 1,099 children aged 9-12 in China were recruited for this cross-sectional study. A semi-quantified food frequency questionnaire (FFQ) was used to assess dietary intake. A priori numerical index, the Chinese Dietary Guidelines Index for Children and Adolescents [CDGI (2021)-C] was utilized to assess dietary quality. Specific DPs were identified by using principal components analysis (PCA). The BMD of the left forearm was assessed using dual-energy X-ray absorptiometry (DXA). Spearman correlation test was conducted to investigate the associations between DPs. Multivariate logistic regression analysis and restricted cubic spline models (RCS) were applied to explore the associations between DPs and BMD. Three distinct DPs were identified: the plant-animal balanced pattern, the grain-tuber-meat pattern, and the bean-dairy pattern. We found a weak but significant positive correlation of the CDGI (2021)-C with the plant-animal balanced pattern (R = 0.318, P < 0.001), and with the bean-dairy pattern (R = 0.266, P < 0.001), respectively. After adjusting for covariates, adherence to the CDGI (2021)-C (Q4 vs. Q1, OR = 0.45, 95% CI: 0.27-0.75), the plant-animal balanced pattern (Q4 vs. Q1, OR = 0.50, 95% CI: 0.31-0.81), and the bean-dairy pattern (Q3 vs. Q1, OR = 0.57, 95% CI: 0.33-0.96) were associated with a lower risk of low BMD. No significant association was observed between the grain-tuber-meat pattern and low BMD (Q4 vs. Q1, OR = 1.09; 95% CI: 0.90-1.31). Adherence to the CDGI (2021)-C and the plant-animal balanced pattern is advantageous for bone health and inversely correlated with the risk of low BMD among school-aged children in China. Additionally, moderate adherence to the bean-dairy pattern may also confer benefits to bone health. A balanced and overall healthy diet should be recommended in our daily life.

Causal effects of Parkinson's disease on the risk of osteoporosis: A two-sample Mendelian randomization study.

Employing a two-sample Mendelian randomization (MR) analysis, we aimed to investigate the potential causal effect of Parkinson disease (PD) on osteoporosis. We conducted an in-depth MR analysis by leveraging extensive genome-wide association study datasets from the International Parkinson Disease Genomics Consortium and the Genetic Factors for Osteoporosis Consortium. We meticulously selected instrumental variables based on strict criteria, including significance thresholds, linkage disequilibrium, and the exclusion of confounding single-nucleotide polymorphisms. Our investigation utilized diverse MR methods, including inverse variance weighted, MR Egger regression, weighted median, and MR-PRESSO, to robustly evaluate the causal relationship. Our comprehensive analysis revealed noteworthy associations between PD and distinct measures of bone mineral density (BMD) (forearm BMD, femoral neck BMD, lumbar spine BMD). Specifically, the inverse variance weighted method underscored potential significant relationships between PD and forearm BMD (P = .037; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00-1.09), femoral neck BMD (P = .034; OR, 1.02; 95% CI, 1.00-1.05), and lumbar spine BMD (P = .043; OR, 1.03; 95% CI, 1.00-1.06). The consistency of results across various methods and sensitivity analyses indicated both robustness and minimal pleiotropy concerns. Through a two-sample MR approach, this study establishes a plausible causal relationship between PD and decreased BMD. The outcomes underscore the urgency of targeted interventions to mitigate bone loss and manage osteoporosis in individuals with PD.

Association between sarcopenia and osteoporosis: the cross-sectional study from NHANES 1999-2020 and a bi-directions Mendelian randomization study.

Osteoporosis (OP) and sarcopenia are prevalent musculoskeletal conditions among the elderly. Nevertheless, the causal relationship between sarcopenia and OP remains a subject of controversy and uncertainty. In this study, we employed cross-sectional analysis and Mendelian randomization (MR) to investigate the intricate relationship between sarcopenia and OP. The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2020, which involved in 116,876 participants. It assessed the correlation between sarcopenia, osteoporosis (OP), and bone mineral density (BMD) using Chi-square tests, T-tests, and a multiple logistic regression model. Additionally, we conducted Mendelian randomization (MR) analysis to investigate the causal effects of sarcopenia-related characteristics (ALM) on OP. We employed IVW, sensitivity analysis, heterogeneity testing, and other methods for MR. The ALM data was sourced from the UK Biobank (n=450,243), while the aggregated data on OP was obtained from GWAS statistics (n=53,236). In this cross-sectional analysis, we observed that in the multivariate logistic regression model, without adjusting for any variables, OP emerged as a risk factor for sarcopenia [OR 95% CI = 1.90 (1.13-3.18), P = 0.02]. Following adjustments for gender, age, BMI, and biochemical variables, OP retained its status as a risk factor for sarcopenia [OR 95% CI = 3.54 (1.91-6.54), P < 0.001]. Moreover, after accounting for all variables, OP emerged as an independent risk factor for sarcopenia [OR 95% CI = 4.57 (1.47-14.22), P = 0.01].In the MR analysis, we uncovered that femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm bone mineral density (FA BMD) exerted a direct causal influence on ALM [FA BMD: OR 95% CI = 1.028 (1.008, 1.049), p = 0.006; FN BMD: OR (95% CI) = 1.131 (1.092, 1.170), p = 3.18E-12; LS BMD: OR (95% CI) = 1.080 (1.062, 1.098), p= 2.86E-19]. Our study has revealed a positive correlation between OP and the prevalence of sarcopenia. It suggests a potentially robust causal relationship between OP and sarcopenia. Notably, OP appears to be associated with a higher likelihood of losing ALM, and a significant loss of ALM may contribute to a decline in LS BMD.

Prediction models incorporating second metacarpal cortical index for osteoporosis in rheumatoid arthritis: Externally validated machine learning models developed using data from the KURAMA cohort.

Osteoporosis and osteopenia are significant concerns in rheumatoid arthritis (RA), predisposing patients to fragility fractures. While dual-energy X-ray absorptiometry (DXA) is the gold standard for bone mineral density (BMD) assessment, simpler screening tools are needed. This study aims to assess the correlation between the second metacarpal cortical index (2MCI) and BMD in RA patients, and to evaluate machine learning (ML) models utilizing 2MCI and clinical parameters for predicting osteoporosis/osteopenia presence and BMD. Data from the KURAMA cohort (n = 302) and an external validation cohort (n = 32) were analyzed. BMD in the hip and forearm was obtained using DXA and 2MCI was calculated from plain hand X-ray. ML models were trained to predict osteoporosis/osteopenia presence and BMD using 2MCI and clinical variables and validated using external cohort. 2MCI correlated significantly with hip and forearm BMD. ML models incorporating 2MCI and other clinical parameters showed good performance in predicting osteoporosis/osteopenia presence and BMD. External validation demonstrated the generalizability of the models. ML models utilizing 2MCI and clinical parameters show promise for osteoporosis screening in RA patients.

Causal relationship between neuroticism and bone mineral density: A univariable and multivariable Mendelian randomization study.

Recent observational studies have indicated that psychiatric disorders were associated with risk of bone mineral density (BMD) reduction. But the causal relationship between neuroticism and BMD remained unclear. By using public genome-wide association study data, a 2-sample bidirectional Mendelian randomization (MR) study was performed to investigate the causal relationship between neuroticism and BMD (heel BMD, forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD). Inverse-variance weighted, weighted median, and MR-Egger were used to assess the causal effects. Multiple sensitivity analyses were conducted to assess the potential bias of the causal estimates. Multivariable MR analysis was used to assess the direct causal effects of neuroticism on BMD with adjustment of common risk factors of BMD reduction. Univariable MR analysis indicated that genetically predicted higher neuroticism was significantly associated with an increased risk of heel BMD reduction (inverse-variance weighted β = -0.039; se = 0.01; P = .0001; Bonferroni-corrected P = .0005) but not with other BMD (forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD) potentially due to limited statistical power. The causal effects remained significant after accounting for the effects of body mass index, smoking, and drinking. Genetic proxy for higher neuroticism was significantly associated with an increased risk of heel BMD reduction. Further studies were warranted to elucidate the underlying biological mechanisms and explore the potential application in disease early screening and management.

Effects of FGF21 overexpression in osteoporosis and bone mineral density: a two-sample, mediating Mendelian analysis.

Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density. We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results. MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively. Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Impact of dairy supplementation on bone acquisition in children's limbs: a 12-month cluster-randomized controlled trial and meta-analysis.

This study evaluated the impact of dairy supplementation on bone acquisition in children's limbs through a cluster-randomized controlled trial and a meta-analysis. The trial involved 315 children (4-6year) from Northwest China, randomized to receive either 390ml of milk daily (n = 215) or 20-30g of bread (n = 100) over 12months. We primarily assessed bone mineral density (BMD) and content (BMC) changes at the limbs, alongside bone-related biomarkers, measured at baseline, the 6th and 12th months. The meta-analysis aggregated BMD or BMC changes in the forearm/legs/calcaneus from published randomized trials involving children aged 3-18years supplemented with dairy foods (vs. control group). Of 278 completed the trial, intention-to-treat analysis revealed significant increases in BMD (4.05% and 7.31%) and BMC (4.69% and 7.34%) in the left forearm at the 6th and 12th months in the milk group compared to controls (P < 0.001). The calcaneus showed notable improvements in BMD (2.01%) and BMC (1.87%) at 6months but not at 12months. Additionally, milk supplementation was associated with beneficial changes in bone resorption markers, parathyroid hormone (- 12.70%), insulin-like growth factor 1 (6.69%), and the calcium-to-phosphorus ratio (2.22%) (all P < 0.05). The meta-analysis, encompassing 894 children, indicated that dairy supplementation significantly increased BMD (SMD, 0.629; 95%CI: 0.275, 0.983) and BMC (SMD, 0.616; 95%CI: 0.380, 0.851) (P < 0.05) in the arms, but not in the legs (P > 0.05). Milk supplementation significantly improves bone health in children's forearms, underscoring its potential as a strategic dietary intervention for bone development. Trial registration NCT05074836.

The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis.

Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished. This study utilized Mendelian Randomization (MR) analysis to explore the causal relationship between BMD and the risk of falling, incorporating linkage disequilibrium score (LDSC) regression for genetic correlation assessment. The primary method was inverse-variance weighted (IVW), supplemented with sensitivity analyses and the causal analysis using summary effect estimates (CAUSE) to address heterogeneity and pleiotropy biases. LDSC analysis indicated significant genetic correlations between BMD at various sites and falling risk (rg range: -0.82 to 0.76, all P < 0.05). IVW analysis, with False Discovery Rate (FDR) correction, showed a protective causal effect of total body BMD (OR = 0.85, 95% CI 0.82-0.88, P = 7.63 × 10-17, PFDR = 1.91 × 10-16), femoral neck BMD (OR = 0.81, 95% CI 0.75-0.88, P = 3.33 × 10-7, PFDR = 5.55 × 10-7), lumbar spine BMD (OR = 0.85, 95% CI 0.79-0.91, P = 9.56 × 10-7, PFDR = 1.20 × 10-6), and heel BMD (OR = 0.82, 95% CI 0.79-0.81, P = 1.69 × 10-39, PFDR = 8.45 × 10-39) on falling risk. No causal relationship was found for forearm BMD (OR = 1.02, 95% CI 0.94-1.11, P = 0.64, PFDR = 0.64). Replication datasets and CAUSE analysis provided causal evidence consistent with the main findings. The study established a causal relationship between BMD at four different sites and the risk of falling, highlighting potential areas for targeted prevention strategies.

Preliminary study of distal forearm bone mineral density in residents of Doi Lo District: Observation and comparison with Mae Chaem, and Omkoi Districts, Chiang Mai Province, Thailand

Background: We previously reported distal forearm bone mineral density (BMD) information for individuals residing in Mae Chaem and Omkoi districts, Chiang Mai Province, Thailand. Objective: This study was aimed to observe distal forearm BMD in residents of Doi Lo District and compare this data with individuals residing in Mae Chaem District and Omkoi District in Chiang Mai Province, Thailand. Materials and methods: Two hundred fifty-one subjects (215 women, 36 men), aged 24 to 69 years, currently reside in Doi Lo District. BMD was measured on the non-dominant distal forearm using peripheral dual-energy X-ray absorptiometry (pDEXA). Subsequently, data from Doi Lo District were compared with data from Mae Chaem District and Omkoi District obtained from earlier studies. Results: Distal forearm BMD decreased, and the prevalence of osteoporosis increased in both females and males across age groups. This trend was consistent with data from Mae Chaem District and Omkoi District. Conclusion: This study demonstrated the prevalence of distal forearm BMD and osteoporosis among females and males in Doi Lo District. The findings from Doi Lo District were consistent with those from Mae Chaem District and Omkoi District in Chiang Mai Province, Thailand. These results provide valuable insights into bone health among residents of Chiang Mai Province, Thailand.

The Impact of Non-alcohol Fatty Liver Disease on Bone Mineral Density is Mediated by Sclerostin by Mendelian Randomization Study.

Non-alcoholic fatty liver disease (NAFLD) has been found to be associated with osteoporosis (OP) in observational studies. However, the precise causal relationship between NAFLD and OP remains unclear. Here, we used Mendelian randomization (MR) to explore the causal relationship. We selected NAFLD-related single-nucleotide polymorphisms from a genome-wide meta-analysis (8434 cases and 434,770 controls) as instrumental variants. We used inverse variance weighted analysis for the primary MR analysis. Furthermore, we used similar methodologies in parallel investigations of other chronic liver diseases (CLDs). We performed sensitivity analyses to ensure the reliability of the results. We observed a causality between NAFLD and forearm bone mineral density (FABMD) (beta-estimate [β]: -0.212; p-value: 0.034). We also found that sclerostin can act as a mediator to influence the NAFLD and FABMD pathways to form a mediated MR network (mediated proportion=8.8%). We also identified indications of causal relationships between other CLDs and OP. However, we were unable to establish any associated mediators. Notably, our analyses did not yield any evidence of pleiotropy. Our findings have implications in the development of preventive and interventional measures aimed at managing low bone mineral density in patients with NAFLD.

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis.

Previous observational studies have observed a correlation between sedentary behavior and osteoporosis. However, conclusions from these studies have been contradictory. To explore the potential causal relationship between sedentary behavior and osteoporosis, we conducted a Mendelian randomization analysis. A two-sample Mendelian randomization was adopted to explore the causal relationship of leisure sedentary behavior with osteoporosis. We employed 5 methods to estimate the causal associations between leisure sedentary behavior and osteoporosis. Univariable Mendelian randomization results provided evidence for the causal relationship of the time spent on computer-use with the bone mineral density estimated by heel quantitative ultrasound (eBMD) (inverse variance weighted [IVW]: β (95% confidence interval [CI]) - 0.150 (-0.270 to -0.031), P = .013; weighted median: β (95%CI) - 0.195 (-0.336 to -0.055), P = .006). Similar associations were observed in the driving forearm bone mineral density (FABMD) (IVW: β (95%CI) - 0.933 (-1.860 to -0.007), P = .048) and driving lumbar spine bone mineral density (IVW: β (95%CI) - 0.649 (-1.175 to -0.124), P = .015). However, we did not find a significant causal relationship between the time spent on watching TV and bone mineral density. Research showed that there was a causal relationship between the time spent on computer use and driving time and eBMD, FABMD, and lumbar spine bone mineral density.

Causal effect of education on bone mineral density: A Mendelian randomization study.

Education level may have some association with the incidence of osteoporosis, but it is elusive if this association is causal. This two-sample Mendelian randomization analysis focused on the causal effect of education level on femoral neck bone mineral density (FN-BMD), forearm BMD, lumbar spine BMD, and heel BMD. Twelve single nucleotide polymorphisms were used as instrumental variables. The results suggested that high education level was associated with improved FN-BMD (beta-estimate: 0.406, 95% confidence interval: 0.061 to 0.751, standard error: 0.176, P-value = .021). There were null association between education and other sites of bone mineral density. Our results found the causal effect of high education level on improved FN-BMD, and improved educational attainment may be beneficial to prevent osteoporosis.

Associations between ultra-distal forearm bone mineral density and incident fracture in women

SummaryBone mineral density measured at the ultra-distal forearm site was associated with any fracture, as well as distal radius fracture in women from a longitudinal cohort study.PurposeFemoral neck (BMDhip) and lumbar spine (BMDspine) bone mineral density (BMD) are routinely used to assess fracture risk. More data are needed to understand how ultra-distal forearm BMD (BMDUDforearm) may assist fracture prediction.MethodsUsing a Lunar DPX-L, Geelong Osteoporosis Study women (n = 1026), aged 40–90 years, had BMD measured. Incident low-trauma fractures were radiologically verified. Using Cox proportional hazard models, hazard ratios (HR) were calculated for BMDUDforearm as a continuous variable (expressed as a one-unit decrease in T-score) and a categorical variable (normal/osteopenia/osteoporosis). Areas under receiver operating characteristics (AUROC) curves were calculated. Analyses were conducted for any fracture and distal radius fractures.ResultsDuring 14,270 person-years of follow-up, there were 318 fractures (85 distal radius). In adjusted models, continuous BMDUDforearm was associated with any (HR 1.26;95%CI 1.15–1.39) and distal radius fractures (HR 1.59;95%CI 1.38–1.83). AUROCs for continuous BMDUDforearm, 33% forearm(BMD33%forearm), BMDhip, BMDspine, and FRAX without BMD were similar for any fracture (p > 0.05). For distal radius fracture, the AUROC for BMDUDforearm was higher than other sites and FRAX (p < 0.05).In adjusted models, those with osteoporosis had a higher likelihood of any fracture (HR 2.12; 95%CI 1.50–2.98). For distal radius fractures, both osteopenia and osteoporosis had a higher risk (HR 4.31; 95%CI 2.59–7.15 and 4.81; 95%CI 2.70–8.58). AUROCs for any fracture were similar for categorical BMD at all sites but lower for FRAX (p < 0.05). For distal radius fractures, the AUROC for BMDUDforearm, was higher than other sites and FRAX (p < 0.05).ConclusionUltra-distal forearm BMD may aid risk assessments for any distal radius fractures.

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.

Cross-Sectional and Longitudinal Associations between Forearm Bone Mineral Density and Anthropometry in Adult Japanese Men and Women.

No consensus exists regarding which anthropometric measurements are related to bone mineral density (BMD), and this relationship may vary according to sex and age. A large Japanese cohort was analyzed to provide an understanding of the relationship between BMD and anthropometry while adjusting for known confounding factors. Our cohort included 10,827 participants who underwent multiple medical checkups including distal forearm BMD scans. Participants were stratified into four groups according to age (≥50 years or <50 years) and sex. The BMD values were adjusted for confounding factors, after which single and partial correlation analyses were performed. The prevalence of osteopenia was plotted for each weight index (weight or body mass index [BMI]) class. Cross-sectional studies revealed that weight was more favorably correlated than BMI in the older group (R=0.278 and 0.212 in men and R=0.304 and 0.220 in women, respectively), whereas weight and BMI were weakly correlated in the younger age groups. The prevalence of osteopenia exhibited a negative linear relationship with weight among older women ≥50 years of age, and an accelerated increase was observed with decreasing weight in older men weighing <50 kg and younger women weighing <60 kg. When weight was replaced with BMI, the prevalence was low in most subgroups classified by weight. Weight, rather than BMI, was the most important indicator of osteopenia but it might not be predictive of future bone loss.

Opportunistic hand radiographs to screen for low forearm bone mineral density: a prospective and retrospective cohort study

BackgroundLow bone mineral density affects 53% of women over age 65 in the US, yet many are unaware and remain untreated. Underdiagnosis of forearm osteoporosis and related fragility fractures represent missed warning signs of more deadly, future fractures. This study aimed to determine if hand radiographs could serve as early, simple screening tools for predicting low forearm bone mineral density (BMD).MethodsWe evaluated posterior-anterior (PA) hand radiographs (x-rays) and Dual-energy X-ray absorptiometry (DXA) scans of 43 participants. The ratio of the intramedullary cavity to total cortical diameter of the second metacarpal (second metacarpal cortical percentage (2MCP)) was used as a potential diagnostic marker. Mixed-effects linear regression was performed to determine correlation of 2MCP with BMD from various anatomic regions. Repeated measures ANOVAs were used to compare BMD across sites. An optimal 2MCP cutoff for predicting forearm osteopenia and osteoporosis was found using Receiver Operating Curves.Results2MCP is directly correlated with BMD in the forearm. The optimal 2MCP of 48.3% had 80% sensitivity for detecting osteoporosis of the 1/3 distal forearm. An 2MCP cutoff of 50.8% had 84% sensitivity to detect osteoporosis of the most distal forearm. Both 2MCP cutoffs were more sensitive at predicting forearm osteoporosis than femoral neck T-scores.ConclusionsThese findings support the expansion of osteoporosis screening to include low-cost hand x-rays, aiming to increase diagnosis and treatment of low forearm BMD and fractures. Proposed next steps include confirming the optimal 2MCP cutoff at scale and integrating automatic 2MCP measurements into PAC systems.

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.

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

BackgroundChronic liver diseases constitute a major global public health burden, posing a substantial threat to patients’ daily lives and even survival due to the potential development of musculoskeletal disorders. Although the relationship between chronic liver diseases and musculoskeletal disorders has received extensive attention, their causal relationship has not been comprehensively and systematically investigated.MethodsThis study aimed to assess the causal relationships between viral hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC), liver cirrhosis, and hepatocellular carcinoma (HCC) with osteoporosis, osteoarthritis, and sarcopenia through bidirectional Mendelian randomization (MR) research. The traits related to osteoporosis and osteoarthritis included both overall and site-specific phenotypes, and the traits linked to sarcopenia involved indicators of muscle mass and function. Random-effect inverse-variance weighted (IVW), weighted median, MR-Egger, and Causal Analysis Using the Summary Effect Estimates were used to evaluate causal effects, with IVW being the main analysis method. To enhance robustness, sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, MR-PRESSO global test, funnel plots, leave-one-out analyses, and latent causal variable model.ResultsThe forward MR analysis indicated that PSC can reduce forearm bone mineral density (beta = − 0.0454, 95% CI − 0.0798 to − 0.0110; P = 0.0098) and increase the risk of overall osteoarthritis (OR = 1.012, 95% CI 1.002–1.022; P = 0.0247), while HCC can decrease grip strength (beta = − 0.0053, 95% CI − 0.008 to − 0.0025; P = 0.0002). The reverse MR analysis did not find significant causal effects of musculoskeletal disorders on chronic liver diseases. Additionally, no heterogeneity or pleiotropy was detected.ConclusionsThese findings corroborate the causal effects of PSC on osteoporosis and osteoarthritis, as well as the causal impact of HCC on sarcopenia. Thus, the implementation of comprehensive preventive measures is imperative for PSC and HCC patients to mitigate the risk of musculoskeletal disorders, ultimately improving their quality of life.

Exploring causality between bone mineral density and frailty: A bidirectional Mendelian randomization study.

The bidirectional correlation between low bone mineral density (BMD) and frailty, despite its extensive documentation, still lacks a conclusive understanding. The objective of this Mendelian randomization (MR) study is to investigate the bidirectional causal relationship between BMD and frailty. We utilized summary statistics data for BMD at different skeletal sites-including heel BMD (e-BMD, N = 40,613), forearm BMD (FA-BMD, N = 8,143), femoral neck BMD (FN-BMD, N = 32,735), and lumbar spine BMD (LS-BMD, N = 28,489), alongside frailty index (FI, N = 175,226) data in participants of European ancestry. MR analysis in our study was conducted using well-established analytical methods, including inverse variance weighted (IVW), weighted median (WM), and MR-Egger approaches. We observed negative causal estimates between genetically predicted e-BMD (IVW β = - 0.020, 95% confidence interval (CI) = - 0.038, - 0.002, P = 0.029) and FA-BMD (IVW β = -0.035, 95% CI = -0.066, -0.004, P = 0.028) with FI. However, the results did not reach statistical significance after applying the Bonferroni correction, with a significance threshold set at P < 0.0125 (0.05/4). There was no causal effect of FN-BMD (IVW β = - 0.024, 95% CI = -0.052, 0.004, P = 0.088) and LS-BMD (IVW β = - 0.005, 95% CI = -0.034, 0.024, P = 0.749) on FI. In the reverse Mendelian randomization (MR) analysis, we observed no causal effect of FI on BMD at various skeletal sites. Our study provides support for the hypothesis that low BMD may be a potential causal risk factor for frailty, but further research is needed to confirm this relationship. However, our findings did not confirm reverse causality.

Impact of Adding Distal Forearm Bone Mineral Density Measurement to Axial Bone Mineral Density Measurement for the Diagnosis of Osteoporosis: Prevalence and Risk Factors for Diagnostic Discordance

Background: Studies have demonstrated the superiority of distal forearm bone mineral density (BMD) measurement over axial BMD measurement for prediction of osteoporotic fractures of distal radius. However, distal forearm BMD measurement is not routinely performed at most centers. Objective: To demonstrate the prevalence of discordance in diagnosis of osteoporosis using axial and distal forearm BMD measurement, and to assess whether age and other potential risk factors can predict major discordance. Materials and Methods: Postmenopausal women aged 45 years or older and men aged 50 years or older who underwent lumbar spine, hip, and distal forearm BMD measurement at Prompt Health Center, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand, between January 2021 and December 2021 were recruited. The T-scores of axial site and distal forearm were categorized based on World Health Organization classification to determine the prevalence of diagnostic discordance. Major discordance was defined as having one osteoporotic and one normal T-score. Factors potentially associated with major discordance were explored using univariate and multivariate logistic regression models. Results: Eight hundred eighty-one participants including 621 women and 260 men with a mean age of 59.2±6.7 years were analyzed. There were 13.2% participants diagnosed with osteoporosis of the axial site, and 16.0% of the one-third (1/3) radius. The rates of major discordance, minor discordance, and concordance between axial and 1/3 radius T-scores were 3.2%, 40.5%, and 56.3%, respectively. Age of 65 years or older was significantly associated with major axial and 1/3 radius T-score discordance, with an adjusted odds ratio of 2.7 and 95% confidence interval 1.24 to 5.87 (p=0.012). Conclusion: Diagnostic discordance is observed for at least one-third of the participants using axial and distal forearm BMD measurement. The age of 65 years or older is a risk factor for major discordance. Keywords: Bone mineral density; Osteoporosis; Spine; Hip; Distal forearm; Discordance