Bone Mineral Density Estimation Research Articles

Asynchronous calibration of a CT scanner for bone mineral density estimation: sources of error and correction

Asynchronous calibration of a CT scanner for bone mineral density estimation: sources of error and correction

Knowledge, Attitudes, Practices, and Awareness Levels Among Indian Postmenopausal Women About Osteoporosis and Its Relationship With Sociodemographic Factors: A Cross-Sectional Study From Northern India.

Background Osteoporosis is a silent disease and can be prevented by providing correct and appropriate information to the individuals at risk. Therefore, we aim to find out the levels of knowledge, attitudes, and behaviors of postmenopausal women, the highest-risk group. Methods Between May 2021 and December 2023, a cross-sectional study was done in the Military Hospital in Ambala, India, in 1326 postmenopausal women of age between 45 and 70 years who visited the outpatient department of orthopedics and who previously had a measure of bone mineral density (BMD) or estimation of BMD. All patients participating in the study received a questionnaire that assessed the level of knowledge, attitudes, and behaviors related to osteoporosis. The Osteoporosis Knowledge Assessment Tool (OKAT) was used to assess these parameters. Results The mean age was 60±3.1 years. The mean score for osteoporosis awareness was 6/20 points. A total of 983 (73.13%) had no knowledge about osteoporosis, and 221 (16.66%) had higher knowledge. Knowledge about osteoporosis was low with a mean knowledge score of 7.44±3.16 and a median of 7.2.It was found that those who graduated had some knowledge regarding osteoporosis with the help of either a hospital staff or a family member who had a history of osteoporosis. Conclusions Even among postmenopausal women who know they are at risk and should have BMD, knowledge, attitudes, and behaviors about osteoporosis were found to be quite low. In addition, education and mass communications are needed to increase awareness among women of this age about improving bone health.

SharePro: an accurate and efficient genetic colocalization method accounting for multiple causal signals.

Colocalization analysis is commonly used to assess whether two or more traits share the same genetic signals identified in genome-wide association studies (GWAS), and is important for prioritizing targets for functional follow-up of GWAS results. Existing colocalization methods can have suboptimal performance when there are multiple causal variants in one genomic locus. We propose SharePro to extend the COLOC framework for colocalization analysis. SharePro integrates linkage disequilibrium (LD) modeling and colocalization assessment by grouping correlated variants into effect groups. With an efficient variational inference algorithm, posterior colocalization probabilities can be accurately estimated. In simulation studies, SharePro demonstrated increased power with a well-controlled false positive rate at a low computational cost. Compared to existing methods, SharePro provided stronger and more consistent colocalization evidence for known lipid-lowering drug target proteins and their corresponding lipid traits. Through an additional challenging case of the colocalization analysis of the circulating abundance of R-spondin 3 GWAS and estimated bone mineral density GWAS, we demonstrated the utility of SharePro in identifying biologically plausible colocalized signals. SharePro for colocalization analysis is written in Python and openly available at https://github.com/zhwm/SharePro_coloc.

Comparison of Singh’s index in view of osteoporosis in patient with in tertrochanteric fracture and intracapsular fracture

Background: Osteoporosis is a progressive, systemic, skeletal disease with low bone mass. Diagnosing osteoporosis in practice is a major challenge, where resources are limited and costly. Measurement of osteoporosis through Singh’s index in proximal femur fracture patients is consistent with Bone Mineral Density estimation like DEXA scan. Singh’s index is a reliable, reproducible and easily available investigation for osteoporosis. The aim of this study is to evaluate the Singh’s index of the patients with inter-trochanteric and intra-capsular fracture. Methods: A retrospective observational study of 20 IT and IC fracture each. Singh’s index evaluated from the X-rays at time of fracture presentation. Other required information collected at presentation. Results: Out of 40 Patients, 6 had Singh's Index Grade 1 (15%), 11 had Grade 2 (27.5%), 10 had Grade 3 (25%), 7 had Grade 4 (17.5%), 6 had Grade 5 (15%), 0 Patients had Singh’s index Grade 6. There was no noticeable significant variation in relation of gender with the type of fracture. Patients with higher age tend to have a lower grade of Singh’s index. Conclusions: Singh’s Index indeed represents bone quality and a fall in the grades predisposes to fractures. Inter trochanteric fractures are common in the older age group with poor Singh’s index (<3) compared to the relatively younger age group with Singh’s index around 3. Gender, exercise, history of hypertension and diabetes, sunlight exposure, etc. has no significant impact on Singh's Index. Age is deciding factor for Singh’s Index.

Systemic Inflammatory Regulators Associated with Osteoporosis: A Bidirectional Mendelian Randomization Study.

To elucidate the precise upstream and downstream regulatory mechanisms of inflammatory factors in osteoporosis (OP) progression and to establish a causal relationship between inflammatory factors and OP. We conducted bidirectional Mendelian randomization (MR) analyses using data for 41 cytokines obtained from three independent cohorts comprising 8293 Finnish individuals. Estimated bone mineral density (eBMD) data were derived from 426,824 UK Biobank White British individuals (55% female) and fracture data from 416,795 UK Biobank participants of European ancestry. The inverse variance-weighted method was the primary MR analysis approach. We employed other methods as complementary approaches for mutual corroboration. To test for pleiotropy and heterogeneity, we used the MR-Egger regression, MR-pleiotropy residual sum and outlier global test, and the Cochrane Q test. Macrophage inflammatory protein (MIP)-1α and interleukin (IL)-12p70 expression associated negatively and causally with eBMD (β = -0.017 [MIP-1α], β = -0.011 [IL-12p70]). Conversely, tumor necrosis factor-related apoptosis-inducing ligand was associated with a decreased risk of fractures (Odds Ratio: 0.980). Additionally, OP influenced the expression of multiple inflammatory factors, including growth-regulated oncogene-α, interferon-gamma, IL-6, beta nerve growth factor, and IL-2. Finally, we discovered complex bidirectional causal relationships between IL-8, IL-10, and OP. Specific inflammatory factors may contribute to OP development or may be causally affected by OP. We identified a bidirectional causal relationship between certain inflammatory factors and OP. These findings provide new perspectives for early prediction and targeted treatment of OP. Larger cohort studies are necessary in the future to further validate these findings.

Associations of residential greenness with bone mineral density and osteoporosis: the modifying effect of genetic susceptibility

ObjectivesTo investigate the associations of residential greenness with bone mineral density and incident osteoporosis, and further evaluate the potential modifying effect of genetic susceptibility.MethodsWe used the Normalised Difference Vegetation Index...

Bone mineral density estimation from a plain X-ray image by learning decomposition into projections of bone-segmented computed tomography.

Osteoporosis is a prevalent bone disease that causes fractures in fragile bones, leading to a decline in daily living activities. Dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) are highly accurate for diagnosing osteoporosis; however, these modalities require special equipment and scan protocols. To frequently monitor bone health, low-cost, low-dose, and ubiquitously available diagnostic methods are highly anticipated. In this study, we aim to perform bone mineral density (BMD) estimation from a plain X-ray image for opportunistic screening, which is potentially useful for early diagnosis. Existing methods have used multi-stage approaches consisting of extraction of the region of interest and simple regression to estimate BMD, which require a large amount of training data. Therefore, we propose an efficient method that learns decomposition into projections of bone-segmented QCT for BMD estimation under limited datasets. The proposed method achieved high accuracy in BMD estimation, where Pearson correlation coefficients of 0.880 and 0.920 were observed for DXA-measured BMD and QCT-measured BMD estimation tasks, respectively, and the root mean square of the coefficient of variation values were 3.27 to 3.79% for four measurements with different poses. Furthermore, we conducted extensive validation experiments, including multi-pose, uncalibrated-CT, and compression experiments toward actual application in routine clinical practice.

Causal influence of muscle weakness on cardiometabolic diseases and osteoporosis

The causal roles of muscle weakness in cardiometabolic diseases and osteoporosis remain elusive. This two-sample Mendelian randomization (MR) study aims to explore the causal roles of muscle weakness in the risk of cardiometabolic diseases and osteoporosis. 15 single nucleotide polymorphisms (SNPs, P < 5 × 10−8) associated with muscle weakness were used as instrumental variables. Genetic predisposition to muscle weakness led to increased risk of coronary artery disease (inverse variance weighted [IVW] analysis, beta-estimate: 0.095, 95% confidence interval [CI]: 0.023 to 0.166, standard error [SE]:0.036, P-value = 0.009) and reduced risk of heart failure (weight median analysis, beta-estimate: − 0.137, 95% CI − 0.264 to − 0.009, SE:0.065, P-value = 0.036). In addition, muscle weakness may reduce the estimated bone mineral density (eBMD, weight median analysis, beta-estimate: − 0.059, 95% CI − 0.110 to − 0.008, SE:0.026, P-value = 0.023). We found no MR associations between muscle weakness and atrial fibrillation, type 2 diabetes or fracture. This study provides robust evidence that muscle weakness is causally associated with the incidence of coronary artery disease and heart failure, which may provide new insight to prevent and treat these two cardiometabolic diseases.

Bone Mineral Density Derived from Cardiac CT Scans: Using Contrast Enhanced Scans for Opportunistic Screening

Purpose: Osteoporosis is under-diagnosed and often co-exists with other diseases. Very low bone mineral density (BMD) indicates risk of osteoporosis and opportunistic screening for low BMD in CT-scans has been suggested. In a non-contrast enhanced thoracic CT scan, the scan-field-of-view includes vertebrae enabling BMD estimation. However, many CT scans are obtained by administration of contrast material. If the impact of contrast enhancement on BMD measurements could be quantified, considerably more patients are eligible for screening. Methods: This study investigated the impact of intravenous contrast on thoracic BMD measurements in cardiac CT scans pre- and post-contrast, including different contrast trigger levels of 130 and 180 Hounsfield units (HU). BMD was measured using quantitative CT with asynchronous calibration. Results: In 195 participants undergoing cardiac CT (mean age 57±9 years, 37 % females) contrast increased mean thoracic BMD from 116±33 mg/cm3 (non-enhanced CT) to 130±38 mg/cm3 (contrast-enhanced CT) (p<0.001). Using clinical cut-off values for very low (<80 mg/cm3) and low BMD (<120 mg/cm3) showed that 24 % (47/195 participants) were misclassified when BMD was measured on contrast-enhanced CT-scans. Of the misclassified patients, 6 % (12/195 participants) were categorized as having low BMD despite having very low BMD on the non-enhanced images. Contrast-CT using a higher contrast trigger level showed a significant increase in BMD compared to the lower trigger level (119±32 vs. 135±40 mg/cm3, p<0.01). Conclusion: For patients undergoing cardiac CT, using contrast-enhanced images to assess BMD entails substantial overestimation. Contrast protocol trigger levels also affect BMD measurements. Adjusting for these factors is needed before contrast-enhanced images can be used clinically. Mini abstract: Osteoporosis is under-diagnosed. Contrast-enhanced CT made to examine other diseases might be utilized simultaneously for bone mineral density (BMD) screening. These scans, however, likely entails overestimation of BMD due to the effect of contrast. Adjusting for this effect is needed before contrast-enhanced images can be implemented clinically for BMD screening.

Genetic Correlation, Shared Loci, and Causal Association Between Sex Hormone-Binding Globulin and Bone Mineral Density: Insights From a Large-Scale Genomewide Cross-Trait Analysis.

Although the impact of sex hormones on bone metabolism is well-documented, effect of their primary modulator, sex hormone-binding globulin (SHBG), remains inconclusive. This study aims to elucidate the genetic overlap between SHBG and heel estimated bone mineral density (eBMD), a widely-accepted tool for osteoporosis management and fracture risk assessment. Using summary statistics from large-scale genomewide association studies conducted for SHBG (N = 370,125), SHBG adjusted for body mass index (SHBGa, N = 368,929), and eBMD (N = 426,824), a comprehensive genomewide cross-trait approach was performed to quantify global and local genetic correlations, identify pleiotropic loci, and infer causal associations. A significant overall inverse genetic correlation was found for SHBG and eBMD (rg = -0.11, p = 3.34 × 10-10 ), which was further supported by the significant local genetic correlations observed in 11 genomic regions. Cross-trait meta-analysis revealed 219 shared loci, of which seven were novel. Notably, four novel loci (rs6542680, rs8178616, rs147110934, and rs815625) were further demonstrated to colocalize. Mendelian randomization identified a robust causal effect of SHBG on eBMD (beta = -0.22, p = 3.04 × 10-13 ), with comparable effect sizes observed in both men (beta = -0.16, p = 1.99 × 10-6 ) and women (beta = -0.19, p = 2.73 × 10-9 ). Replacing SHBG with SHBGa, the observed genetic correlations, pleiotropic loci and causal associations did not change substantially. Our work reveals a shared genetic basis between SHBG and eBMD, substantiated by multiple pleiotropic loci and a robust causal relationship. Although SHBG has been implicated in preventing and screening aging-related diseases, our findings support its etiological role in osteoporosis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The rate of disuse osteopenia in admitted, non-weight-bearing patients.

Disuse osteopenia is a well-recognized consequence of prolonged physical inactivity, but its rate after orthopaedic injuries necessitating non-weight-bearing is not well studied. The purpose of this study was to estimate the rate of disuse osteopenia at the lumbar spine and proximal femur in patients with lower extremity trauma admitted to the hospital. We performed a retrospective chart review of patients with lower extremity trauma with a period of strict non-weight-bearing between completion of two computed tomography (CT) scans. The radiodensity of the proximal femur or lumbar vertebrae was measured from the earliest and latest available CT scans within the non-weight-bearing timeframe. The change in estimated bone mineral density (eBMD) was calculated as a proxy for disuse osteopenia. A total of 189,111 patients were screened, with 17 patients in the proximal femur group and 15 patients in the lumbar spine group meeting inclusion and exclusion criteria. The average rate of change in eBMD of the proximal femur was a decrease of 7.54 HU/day, 95% confidence interval(CI) [3.65, 11.43]. The average rate of change in eBMD of the lumbar spine was an increase of 1.45 HU/day, 95% CI [-3.15, 6.06]. In admitted, non-weight-bearing orthopaedic trauma patients, our novel study suggests that the proximal femur experiences disuse osteopenia during periods of non-weight-bearing, although this finding was not observed at the lumbar spine. The clinical significance of this data underscores the important consideration of disuse osteopenia by all physicians when caring for patients that may require non-weight-bearing restrictions.

Spina bifida and cardiorespiratory profile: the impact of leisure sport activities on physical fitness.

The aim of the present study is to evaluate a population of young patients affected by Spina Bifida (SB) to describe their cardiorespiratory function and bone mineral density profile, analyzing any differences between people performing and those who do not perform sports activity. The study also aimed to rule out possible congenital heart disease associated with spina bifida, considering the common origin of certain cardiac structures with those found to be altered in SB patients. Thirty-four young patients, aged between 12 and 22years, diagnosed with spinal dysraphism (SD), have been clinically described and, in order to evaluate their physical fitness, functional capacity and bone mass, almost all of them underwent a complete cardiorespiratory assessment, including electrocardiogram (ECG), echocardiogram, Cardiopulmonary Exercise Test (CPET), body composition analysis using bioimpedance analysis (BIA) and Dual Energy X-ray Absorptiometry (DEXA), as well as the estimation of bone mineral density (BMD) with Computerized Bone Mineralometry (CBM). Collected data demonstrated that only 35% of the subjects practiced physical activity during the week. BMI and percentage FM values were pathological in at least 50% of the population. On cardiological investigations (ECG and echocardiogram), no significant alterations were found. In all patients who performed CPET (79.4%), pathological values of the main functional capacity parameters were revealed, especially peak oxygen consumption (VO2 peak), even when corrected for BCM or FFM estimated at BIA and DEXA, respectively. In the CBM analysis, out of 27 patients in whom the femoral T-score was evaluated, a condition of osteopenia was revealed in 40.7% of the patients (11/27) and osteoporosis in 18.5% (5/27); out of 27 patients in whom the lumbar T-score was evaluated, 37% of the patients showed osteopenia (10/27) and 29.6% osteoporosis (8/27). When the comparison between exercising and non-exercising patients was performed, the only statistically significant difference that emerged was the median lumbar T-score value, which appeared lower in the group not performing physical activity (p = 0,009). The extensive cardiorespiratory evaluation, including CPET, of our cohort of spina bifida patients showed altered values of the main parameters related to cardiorespiratory fitness and is the only study in the literature that analysed bone mineralization values in physically active and sedentary spina bifida patients and demonstrated a statistically significant difference. Furthermore, it is the only study to date that investigated the possible association of congenital heart diseases with SD, without demonstrating the existence of pathological conditions.

Opportunistic CT-Based Hounsfield Units Strongly Correlate with Biomechanical CT Measurements in the Thoracolumbar Spine.

Retrospective cohort study. Hounsfield units (HUs) are known to correlate with clinical outcomes, but no study has evaluated how they correlate with biomechanical computed tomography (BCT) and dual-energy x-ray absorptiometry (DXA) measurements. Low bone mineral density (BMD) represents a major risk factor for fracture and poor outcomes following spine surgery. DXA can provide regional BMD measurements but has limitations. Opportunistic HUs provide targeted BMD estimates; however, they are not formally accepted for diagnosing osteoporosis in current guidelines. More recently, BCT analysis has emerged as a new modality endorsed by the International Society for Clinical Densitometry for assessing bone strength. Consecutive cases from 2017 to 2022 at a single institution were reviewed for patients who underwent BCT in the thoracolumbar spine. BCT-measured vertebral strength, trabecular BMD, and the corresponding American College of Radiology Classification were recorded. DXA studies within three months of the BCT were reviewed. Pearson Correlation Coefficients were calculated, and receiver-operating characteristic curves were constructed to assess the predictive capacity of HUs. Threshold analysis was performed to identify optimal HU values for identifying osteoporosis and low BMD. Correlation analysis of 114 cases revealed a strong relationship between HUs and BCT vertebral strength ( r =0.69; P <0.0001; R2 =0.47) and trabecular BMD ( r =0.76; P <0.0001; R2 =0.58). However, DXA poorly correlated with opportunistic HUs and BCT measurements. HUs accurately predicted osteoporosis and low BMD (Osteoporosis: C =0.95, 95% CI 0.89-1.00; Low BMD: C =0.87, 95% CI 0.79-0.96). Threshold analysis revealed that 106 and 122 HUs represent optimal thresholds for detecting osteoporosis and low BMD. Opportunistic HUs strongly correlated with BCT-based measures, while neither correlated strongly with DXA-based BMD measures in the thoracolumbar spine. HUs are easy to perform at no additional cost and provide accurate BMD estimates at noninstrumented vertebral levels across all American College of Radiology-designated BMD categories.

Estimation of Bone Mineral Density in the Femoral Neck and Lumbar Spine using Texture Analysis of Chest and Pelvis Computed Tomography Hounsfield Unit.

This study aimed to establish an academic basis for using a computed tomography (CT) model for predicting osteoporosis in the clinical setting by illustrating the effectiveness of morphometric texture analysis. We introduce texture analysis and quantitative approaches using CT Hounsfield units (HU) to screen osteoporosis. From March 6th, 2013, to August 11th, 2020, a total of 4,333 cases (1,766 patients) were included in the study. After applying exclusion criteria concerning the patient status and scan interval between CT and DXA, we selected only 1,647 samples (736 patients) and analyzed both their CT and DXA bone mineral density (BMD) results. BMD was measured in the femoral neck and L1 spine body. A region of interest (ROI) was extracted from each patient's CT as the maximum trabecular area of the L1 spine body and femoral neck. A total of 45 texture features were extracted from every ROI using gray-level co-occurrence matrices. Machine-learning techniques, including linear regression (LR) and artificial neural network (ANN), were applied to predict BMD. We assigned samples to (1) Set 1 (857 lumbar spine samples in chest model, L1 spine DXA BMD), (2) Set 2 (392 lumbar spine samples in lumbar spine CT model, L1 spine DXA BMD), (3) Set 3 (1,249 lumbar spine samples in both chest and lumbar spine CT model, L1 spine DXA BMD), (4) Set 4 (398 femoral neck samples in hip and pelvis CT model, femoral neck DXA BMD), and (5) Set 5 (a total of 1,647 samples). When we applied LR, the correlation coefficients between estimated and reference values for Sets 1, 2, 3, and 4 were 0.783, 0.784, 0.757, and 0.652, respectively. For total samples (Set 5), LR and ANN provided correlation coefficients of 0.707 and 0.782, respectively. The modality using morphometric texture analysis with CT HU can be an additional diagnostic tool for osteoporosis and an alternative for DXA.

MRI-based vertebral bone quality score: relationship with age and reproducibility.

The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3months. This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.

Exploring the Paradox of Bone Mineral Density in Type 2 Diabetes: A Comparative Study Using Opportunistic Chest CT Texture Analysis and DXA.

This study aimed to validate the application of CT texture analysis in estimating Bone Mineral Density (BMD) in patients with Type 2 Diabetes (T2D) and comparing it with the results of dual-energy X-ray absorptiometry (DXA) in a normative cohort. We analyzed a total of 510 cases (145 T2D patients and 365 normal patients) from a single institution. DXA-derived BMD and CT texture analysis-estimated BMD were compared for each participant. Additionally, we investigated the correlation among 45 different texture features within each group. The correlation between CT texture analysis-estimated BMD and DXA-derived BMD in T2D patients was consistently high (0.94 or above), whether measured at L1 BMD, L1 BMC, total hip BMD, or total hip BMC. In contrast, the normative cohort showed a modest correlation, ranging from 0.66 to 0.75. Among the 45 texture features, significant differences were found in the Contrast V 64 and Contrast V 128 features in the normal group. In essence, our study emphasizes that the clinical assessment of bone health, particularly in T2D patients, should not merely rely on traditional measures, such as DXA BMD. Rather, it may be beneficial to incorporate other diagnostic tools, such as CT texture analysis, to better comprehend the complex interplay between various factors impacting bone health.

Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization.

In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors. We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis-SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03-1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01-1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (β=0.24 [95% CI 0.02-0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04-1.15]), but otherwise had attenuated effects. This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors.

Converging evidence from exome sequencing and common variants implicates target genes for osteoporosis.

In this study, we leveraged the combined evidence of rare coding variants and common alleles to identify therapeutic targets for osteoporosis. We undertook a large-scale multiancestry exome-wide association study for estimated bone mineral density, which showed that the burden of rare coding alleles in 19 genes was associated with estimated bone mineral density (P < 3.6 × 10-7). These genes were highly enriched for a set of known causal genes for osteoporosis (65-fold; P = 2.5 × 10-5). Exome-wide significant genes had 96-fold increased odds of being the top ranked effector gene at a given GWAS locus (P = 1.8 × 10-10). By integrating proteomics Mendelian randomization evidence, we prioritized CD109 (cluster of differentiation 109) as a gene for which heterozygous loss of function is associated with higher bone density. CRISPR-Cas9 editing of CD109 in SaOS-2 osteoblast-like cell lines showed that partial CD109 knockdown led to increased mineralization. This study demonstrates that the convergence of common and rare variants, proteomics and CRISPR can highlight new bone biology to guide therapeutic development.

Assessment of osteoporosis in patients with type 2 diabetes mellitus: A study from the central region of Saudi Arabia.

To understand the impact of diabetes on bone mineral density and whether it increases the likelihood of osteoporosis. This study was performed on 327 Saudis (aged >40 years) who were screened for osteoporosis and diabetes mellitus (DM). The levels of osteoporosis were determined by an estimation of Bone mineral density (BMD) using a DEXA scan examination. The data on BMD from diabetic subjects were compared with healthy nondiabetic controls. Out of 327 enrolled subjects, 38 (11.6%) were found to be osteoporotic, whereas 138 (42.2%) had DM. The data showed that the number of patients with osteoporosis in the DM group was 14 (36.8%), significantly lower than in nondiabetic patients, 21 (55.2%) (p=0.0015). Notably, the data showed no significant difference in the mean BMD of the femur in patients with DM (0.926 g/cm2) and non-diabetes (0.936 g/cm2) (p=0.280; T-score p=0.4746). The mean BMD levels in the spine of the DM study group (1.049 g/cm2) were significantly higher when compared with nondiabetic healthy controls (0.990 g/cm2) (p=0.0031). Patients with diabetes had higher lumbar BMD than nondiabetics, although femoral BMD was similar. Patients with diabetes have a lower osteoporosis risk than nondiabetics.

Comparative analysis of bone outcomes between quantitative ultrasound and dual-energy x-ray absorptiometry from the UK Biobank cohort

SummaryThis large cohort study investigated reliability and validity of heel ultrasound to estimate bone mineral density in adults. Reliability calculated between left and right heels was relatively poor and so was criterion validity assessed relative to dual-energy X-ray absorptiometry. Heel ultrasound should be used cautiously when estimating bone mineral density.IntroductionCalcaneal quantitative ultrasound (QUS) may be used as a safe, low cost, and portable means to estimate bone mineral density (BMD) in large cohorts. The purpose of this study was to quantify the reliability and validity of QUS in comparison to dual-energy X-ray absorptiometry (DXA), which is the reference method for BMD measurement and diagnoses of osteopenia and osteoporosis.MethodsBone outcomes measured on the large UK Biobank cohort were used. The reliability of QUS estimated BMD was quantified by comparing values obtained from the left and right heel measured in the same session. Criterion validity was assessed through agreement between QUS and DXA, quantifying correlations, and sensitivity and specificity of osteopenia and osteoporosis diagnoses.ResultsReliability calculations were made using data from over 216,000 participants demonstrating similar QUS BMD values between left and right heels in the absolute scale (Sd of difference for men: 0.12 and 0.07 g·cm−2). However, when expressed in relative scales, including concordance of quartiles, reliability was poor. Agreement between QUS and DXA was quantified using data from 5042 participants. Low to modest correlations (r = 0.29 to 0.44) were obtained between multiple QUS variables and DXA BMD, with sensitivity identified as very poor (0.05 to 0.23) for osteoporosis, and poor (0.37 to 0.62) for osteopenia diagnoses.ConclusionsThe findings of this large comparative analysis identify that whilst calcaneal QUS has the potential to produce reliable absolute BMD measurements and demonstrate modest associations with DXA BMD measures, use of that information to make relative statements about participants in the context of the larger population or to appropriately diagnose osteopenia or osteoporosis may be severely limited.