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Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid–base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems. [ABSTRACT FROM AUTHOR]

Background: SELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.5-year natural history follow-up showed that 90% of the patients had low bone quality, respiratory impairments were found in all SELENON-RM and most of the LAMA2-MD patients, and many had cardiac risk factors. However, further extensive knowledge on long-term natural history data, and clinical and functional outcome measures is needed to reach trial readiness. Therefore, we extended the natural history study with 3- and 5-year follow-up visits (Extended LAST STRONG). Methods: The Extended LAST STRONG is a long-term natural history study in Dutch-speaking patients of all ages diagnosed with genetically confirmed SELENON-RM or LAMA2-MD, starting in September 2023. Patients visit our hospital twice over a period of 2 years to complete a 5-year follow up from the initial LAST-STRONG study. At both visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, muscle ultrasound, respiratory assessments (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), Dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years), X-ray of the left hand (age ≤ 17 years), lower extremity MRI (age ≥ 10 years), accelerometry for 8 days (age ≥ 2 years), and questionnaires (patient report and/or parent proxy; age ≥ 2 years). All examinations are adapted to the patient's age and functional abilities. Disease progression between all subsequent visits and relationships between outcome measures will be assessed. Discussion: This study will provide valuable insights into the 5-year natural history of patients with SELENON-RM and LAMA2-MD and contribute to further selecting relevant and sensitive to change clinical and functional outcome measures. Furthermore, this data will help optimize natural history data collection in clinical care and help develop clinical care guidelines. Trial registration: This study protocol including the patient information and consent forms has been approved by medical ethical reviewing committee ('METC Oost-Nederland'; https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland, file number: 2023–16401). It is registered at ClinicalTrials.gov (NCT06132750; study registration date: 2023-10-05; study first passed date: 2023-11-15). [ABSTRACT FROM AUTHOR]

Sarcopenia is a prevalent condition with significant clinical implications, and it is expected to escalate globally, demanding for effective diagnostic strategies, possibly at an early stage of the disease. Imaging techniques play a pivotal role in comprehensively evaluating sarcopenia, offering insights into both muscle quantity and quality. Among all the imaging techniques currently used for the diagnosis and follow up of sarcopenia, it is possible to distinguish two classes: Rx based techniques, using ionizing radiations, and non-invasive techniques, which are based on the use of safe and low risk diagnostic procedures. Dual-energy x-ray Absorptiometry and Computed Tomography, while widely utilized, entail radiation exposure concerns. Ultrasound imaging offers portability, real-time imaging, and absence of ionizing radiation, making it a promising tool Magnetic Resonance Imaging, particularly T1-weighted and Dixon sequences, provides cross-sectional and high-resolution images and fat-water separation capabilities, facilitating precise sarcopenia quantification. Bioelectrical Impedance Analysis (BIA), a non-invasive technique, estimates body composition, including muscle mass, albeit influenced by hydration status. Standardized protocols, such as those proposed by the Sarcopenia through Ultrasound (SARCUS) Working Group, are imperative for ensuring consistency across assessments. Future research should focus on refining these techniques and harnessing the potential of radiomics and artificial intelligence to enhance diagnostic accuracy and prognostic capabilities in sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Individuals with class II/III obesity have a high percentage of body fat. Assessing body composition in cases of severe obesity can be difficult and controversial both in clinical practice and scientific research. Thus, it is essential to explore the different aspects of evaluating body composition and to discuss the available methods to assess it in this population. Aims: To summarise and discuss the methods used to measure body composition in adults with class II/III obesity and their potential in clinical practice and scientific research. Methods: This is a narrative review using data from PubMed, Scielo, and Lilacs databases. Original articles on body composition analysis in adults with class II/III obesity i.e., a BMI ≥ 35 kg/m2 were eligible. Body composition assessment methods were analysed and described. Results: Some imaging methods produced significantly accurate results. Dual-energy X-ray absorptiometry (DXA) significantly produces accurate results and has been used in clinical studies. However, due to its high cost, it is not applicable in clinical practice. Multifrequency bioelectrical impedance analysis (BIA) has good accuracy and is more appropriate for clinical practice than other methods. We have highlighted several aspects of the importance and applicability of performing body composition analysis in individuals with class II/III obesity. Conclusion: DXA has been considered the most adequate method for clinical research. Multifrequency BIA may be a viable alternative to DXA for use in clinical practice. Assessing body composition and its components is important for people with class II/III obesity. It can help improve the effectiveness of interventions and clinical treatments, especially in reducing the risk of losing muscle mass. Muscle loss can cause sarcopenic obesity and other clinical complications, so understanding body composition is crucial. Assessing body composition can also help understand the impact of interventions on bones and avoid clinical complications. [ABSTRACT FROM AUTHOR]

Background: Maternal preconception overweight status has been reported to be associated with an increased risk of overweight offspring. However, there are no published population-based studies on the association between maternal preconception weight and offspring body fat measured by dual-energy X-ray absorptiometry (DXA). The present population-based retrospective cohort study aimed to examine the association between maternal weight at conception and offspring body fat measured by DXA. Methods: The source population consisted of 5th-grade students (1244 students aged 11 years) registered at 8 municipal elementary schools in Kitakata, Fukuroi, Hamamatsu, and Himeji in Japan. The present analyses included 964 participants who provided complete information. Maternal body mass index (BMI) at conception was calculated using records in the Mother and Child Health Handbook (MCHH). Offspring body fat at age 11 years was measured with the same QDR-4500A DXA instrument in a mobile test room that was brought to each school. With regard to the prediction of excess fat in offspring, the area under the curve (AUC) calculated with receiver operating characteristic curve analysis was used to quantify the diagnostic accuracy of maternal BMI at conception. Results: Adjusted odds ratios for excess body fat in offspring of the overweight mother group (odds ratios, 4.93 to 15.32) were significantly higher than those in the non-overweight mother group. For the prediction of excess offspring fat, AUCs and 95% confidence intervals for maternal BMI at conception were greater than 0.5. Conclusion: Maternal overweight status at conception might be a risk factor for excess body fat in offspring. Maternal BMI values calculated using MCHH data have the potential to distinguish between the presence and absence of excess fat in the next generation. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionAlthough fragility hip fractures (HF) in the South African (SA) population are among the lowest worldwide, the incidence of HF is expected to more than double over the next few decades. Little is known about the contributors to increased hip fracture risk, including low bone mineral density (BMD), in our unique population. In addition, the ability of the recently calibrated SA Fracture Risk Assessment Tool (FRAX) to identify high fracture risk in the SA population accurately has not been validated.A retrospective, descriptive, cohort study of SA postmenopausal women and men ≥ 50 years who presented with fragility HFs was conducted. The ability of clinical risk factors (CRFs) and BMD measured by dual-energy X-ray absorptiometry (DXA), as well as calculated FRAX probability scores, to identify the known high fracture risk in SA patients were evaluated. The SA FRAX tool was used, and a high fracture risk defined if the United States (US) fixed thresholds for major osteoporotic (MOF) and/or HF risk were exceeded (≥ 20% and ≥ 3% over 10 years respectively).A total of 163 patients were included. The most useful predictive CRFs were age and gender, recreational toxins in men, and a history of falls. Most were females (71%), who were older than males. DXA-BMD and FRAX-HF calculations best identified the known high fracture risk in the study cohort. FRAX-MOF calculations performed poorly.Fracture risk assessment tools did not identify the known high fracture risk in all of the elderly study cohort with HF. Clinicians must continue to appreciate the important role of a good clinical assessment to ensure optimal fracture risk prediction. [ABSTRACT FROM AUTHOR]

Introduction: Gender-affirming hormone therapy (GAHT) and gender-affirming surgery (GAS) may be desired by transgender and gender-diverse (TGD) individuals who want to affirm their gender identity. Testosterone is the basis of GAHT for transgender individuals assigned female at birth (AFAB), whereas GAS can involve hysterectomy, bilateral salpingectomy, bilateral oophorectomy (BO), thorax masculinization, and phalloplasty. Our study aimed to evaluate the effects of GAHT on the bone health of TGD AFAB individuals who have undergone or not undergone BO. Methods: This was a single-center, longitudinal study with retrospectively collected data. TGD AFAB GAHT-naïve individuals were enrolled and underwent dual-energy X-ray absorptiometry scans and laboratory tests (hormonal and bone metabolism parameters) at baseline and after 5 and 10 years of GAHT. Results: Two hundred and forty-three TGD AFAB people were included in this study. Seventy-five subjects had completed data for 5 years and 19 subjects for 10 years of GAHT. At baseline, low bone density (Z-score < -2.0) was found in 2.5% (6/243) of subjects for lumbar spine (LS), whereas total hip (TH) and femoral neck (FN) Z-scores and laboratory tests were within the normal female range. After stratifying by physical activity, the physically active group showed significantly higher LS BMD and Z-scores (p = 0.05). Five years after the start of GAHT, a significant reduction in LS (p = 0.05), TH (p = 0.001), and FN (p = 0.01) Zscores was detected. A significant reduction in the Z-scores of all three bone sites was observed only in the subgroup that had undergone BO. After 5 years of GAHT, estradiol levels were significantly decreased compared to those in baseline (p = 0.001). Significantly higher estradiol levels were detected in the 5-year no-BO subgroup compared to those in the 5-year BO subgroup (p = 0.001). A significant reduction in LS and TH Z-scores were observed after 10 years of GAHT. At this time, estradiol levels were significantly decreased compared to those in baseline (p = 0.01). Conclusion: Bone density in TGD AFAB individuals is comparable to that in their peers prior to GAHT and BO, but those subjects who underwent BO had a reduced Z-score at LS, FN, and TH after 5 years and at LS after 10 years of GAHT. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a major chronic disease worldwide and its risk factors have long been investigating in epidemiological studies. Our study aims to develop a body composition-based risk score and integrate it into the Framingham Risk Score (FRS) to improve CVD prediction among well-functioning older adults. We included 1882 older adults from the Health, Aging and Body Composition (Health ABC) study to screen body composition variables obtained from the Dual-energy X-ray absorptiometry (DXA). Three models were developed and compared: the 4-DXA model, the refit FRS, and the refit FRS plus 4-DXA model. C-statistics were 0.62 (95% CI: 0.59, 0.65) for the refit FRS, 0.58 (95% CI: 0.55, 0.61) for the 4-DXA model, and 0.63 (95% CI: 0.60, 0.66) for the refit FRS plus 4-DXA model. Compared to the refit FRS, the refit FRS plus 4-DXA model slightly improved CVD outcome prediction as the discrimination slope, net reclassification index, and the integrated discrimination index were 0.053 (95% CI: 0.041, 0.066), 0.098 (95% CI = – 0.0033, 0.20) and 0.013 (95% CI: 0.0069–0.019). This study provides a model for more accurate risk stratification and draws more attention on DXA-based indices in the clinical setting. It also encourages further research in validating the developed risk score in more diverse population and in investigating a broader range of CVD risk factors. [ABSTRACT FROM AUTHOR]

Epidemiological studies frequently use indices of adiposity related to mortality. However, no studies have validated prediction equations for body composition in adult cancer survivors. We aimed to develop and cross-validate prediction equations for body fat mass (BFM), lean body mass (LBM), trunk fat mass (TFM), and appendicular lean mass (ALM) in adult cancer survivors using sociodemographic, anthropometric, and laboratory test data. This study included adult cancer survivors from the Korean National Health and Nutrition Examination Survey 2008–2011 with complete data on Dual-energy X-ray absorptiometry (DXA) measurements. A total of 310 participants were randomly divided into development and cross-validation groups (5:5 ratio). Age, height, weight, waist circumference, serum creatinine levels, and lifestyle factors were included as independent variables The predictive equations were developed using a multiple linear regression and their predictive performances were primarily evaluated with R2 and Concordance Correlation Coefficient (CCC). The initial equations, which included age, height, weight, and waist circumference, showed different predictive abilities based on sex for BFM (total: R2 = 0.810, standard error of estimate [SEE] = 3.072 kg, CCC = 0.897; men: R2 = 0.848, SEE = 2.217 kg CCC = 0.855; women: R2 = 0.791, SEE = 2.194 kg, CCC = 0.840), LBM (total: R2 = 0.736, SEE = 3.321 kg, CCC = 0.838; men: R2 = 0.703, SEE = 2.450 kg, CCC = 0.774; women: R2 = 0.854, SEE = 2.234 kg, CCC = 0.902), TFM (total: R2 = 0.758, SEE = 1.932 kg, CCC = 0.844; men: R2 = 0.650, SEE = 1.745 kg, CCC = 0.794; women: R2 = 0.852, SEE = 1.504 kg, CCC = 0.890), and ALM (total: R2 = 0.775, SEE = 1.726 kg, CCC = 0.876; men: R2 = 0.805, SEE = 1.320 kg, CCC = 0.817; women: R2 = 0.726, SEE = 1.198 kg, CCC = 0.802). When additional factors, such as creatinine, smoking, alcohol consumption, and physically inactive were included in the initial equations the predictive performance of the equations were generally improved. The prediction equations for body composition derived from this study suggest a potential application in epidemiological investigations on adult cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Obesity, and in particular abdominal obesity, is associated with an increased risk of developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. Obesity causes chronic low-grade inflammation due to increased lipopolysaccharide (LPS) levels which is termed "metabolic endotoxemia." We examined the association of visceral adiposity tissue (VAT) area, circulating endotoxemia markers, and the gut bacterial microbiome in a cohort of aged postmenopausal women. Methods: Fifty postmenopausal women (mean age 78.8 ± 5.3 years) who had existing adipose measurements via dual x-ray absorptiometry (DXA) were selected from the extremes of VAT: n = 25 with low VAT area (45.6 ± 12.5 cm2) and n = 25 with high VAT area (177.5 ± 31.3 cm2). Dietary intake used to estimate the Healthy Eating Index (HEI) score was assessed with a food frequency questionnaire. Plasma LPS, LPS-binding protein (LBP), anti-LPS antibodies, anti-flagellin antibodies, and anti-lipoteichoic acid (LTA) antibodies were measured by ELISA. Metagenomic sequencing was performed on fecal DNA. Female C57BL/6 mice consuming a high-fat or low-fat diet were treated with 0.4 mg/kg diet-derived fecal isolated LPS modeling metabolic endotoxemia, and metabolic outcomes were measured after 6 weeks. Results: Women in the high VAT group showed increased Proteobacteria abundance and a lower Firmicutes/Bacteroidetes ratio. Plasma LBP concentration was positively associated with VAT area. Plasma anti-LPS, anti-LTA, and anti-flagellin IgA antibodies were significantly correlated with adiposity measurements. Women with high VAT showed significantly elevated LPS-expressing bacteria compared to low VAT women. Gut bacterial species that showed significant associations with both adiposity and inflammation (anti-LPS IgA and LBP) were Proteobacteria (Escherichia coli, Shigella spp., and Klebsiella spp.) and Veillonella atypica. Healthy eating index (HEI) scores negatively correlated with % body fat and anti-LPS IgA antibodies levels. Preclinical murine model showed that high-fat diet-fed mice administered a low-fat diet fecal-derived LPS displayed reduced body weight, decreased % body fat, and improved glucose tolerance test parameters when compared with saline-injected or high-fat diet fecal-derived LPS-treated groups consuming a high-fat diet. Conclusions: Increased VAT in postmenopausal women is associated with elevated gut Proteobacteria abundance and immunogenic metabolic endotoxemia markers. Low-fat diet-derived fecal-isolated LPS improved metabolic parameters in high-fat diet-fed mice giving mechanistic insights into potential pro-health signaling mediated by under-acylated LPS isoforms. 7yVbQmTTfsF9b4Af3tznWN Video Abstract [ABSTRACT FROM AUTHOR]

GPR10 and neuropeptide FF receptor 2 (NPFFR2) play important role in the regulation of food intake and energy homeostasis. Understanding the interaction between these receptors and their specific ligands, such as prolactin-releasing peptide, is essential for developing stable peptide analogs with potential for treating obesity. By breeding and characterizing double knockout (dKO) mice fed standard or high-fat diet (HFD), we provide insights into the metabolic regulation associated with the GPR10 and NPFFR2 deficiency. Both WT and dKO mice were subjected to behavioral tests and an oral glucose tolerance test. Moreover, dual-energy X-ray absorptiometry (DEXA) followed by indirect calorimetry were performed to characterize dKO mice. dKO mice of both sexes, when exposed to an HFD, showed reduced glucose tolerance, hyperinsulinemia, and insulin resistance compared with controls. Moreover, they displayed increased liver weight with worsened hepatic steatosis. Mice displayed significantly increased body weight, which was more pronounced in dKO males and caused by higher caloric intake on a standard diet, while dKO females displayed obesity characterized by increased white adipose tissue and enhanced hepatic lipid accumulation on an HFD. Moreover, dKO females exhibited anxiety-like behavior in the open field test. dKO mice on a standard diet had a lower respiratory quotient, with no significant changes in energy expenditure. These results provide insights into alterations associated with disrupted GPR10 and NPFFR2 signaling, contributing to the development of potential anti-obesity treatment. Both authors contributed equally to this work. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndrome 1 (APS1) is an autosomal recessive disorder due to biallelic pathogenic variants in the autoimmune regulator (AIRE) gene that manifests with chronic mucocutaneous candidiasis, primary hypoparathyroidism, and adrenal insufficiency. We report a 39-year-old woman with APS1 who developed partial lipodystrophy during adulthood. She presented with diaper rashes, oral thrush, and tetany during infancy due to candidiasis and hypoparathyroidism. During childhood, she developed hypothyroidism, primary adrenal insufficiency, and ovarian insufficiency. At age 14, she received a sibling-matched allogenic bone marrow transplant due to multiple antibiotic-refractory fungal infections. At age 35, her serum triglycerides were 914 mg/dL (10.32 mmol/L) and she had loss of subcutaneous fat from the upper and lower extremities and hips. A whole-body dual-energy x-ray absorptiometry revealed lower-extremity fat at less than the first percentile. Whole-exome sequencing on DNA extracted from saliva revealed pathogenic variants, p.Leu28Pro and p.Arg257* in AIRE but none in the known lipodystrophy genes. Phage-immunoprecipitation-sequencing revealed the presence of autoantibodies to MAGEB1, MAGEB4, and RFX6, which have been previously reported in APS1. Our case suggests that patients with APS1 may develop partial lipodystrophy due to autoantibodies against novel adipocyte-expressed proteins. A causal relationship of high levels of autoantibodies in our patient to adipose tissue–expressed ODC1, NUCKS1, or FNBP1L and lipodystrophy remains uncertain. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is an osteometabolic disorder characterized by a lesser bone mineral density (BMD) and the disruption of bone tissue micro—architecture, resulting in a greater bone fragility and higher likelihoods of fractures. OP emerges once the bone mass declines faster than the body's capacity to replenish it, leading to a significant reduction in the strength of bone. OP impacts each and every bone throughout the body and provides no clinical signs until a fracture happens. Aging leads to the reduction in BMD, and the rate of percentage of fractures rises over time, usually causing mortality and morbidity. Numerous BMD evaluation methods are available, and they are used in a variety of settings by considering the location of the fracture. Dual-energy x-ray absorptiometry (DEXA/DXA) is recognized as the gold standard for predicting the fracture, since it is the most advanced, technologically affirmed, and also has excellent performance. According to the findings, most researchers do not endeavour the identification and the segmentation of low bone masses from DEXA images. Medical image segmentation supports in analyzing and visualizing the bone's low bone mass. The envisaged hybrid approach, that integrates GLCM for feature extraction and AlexNet for a low bone mass variation classification, provides segmented images that assist in categorizing bone health as normal, osteopenia, or osteoporosis. The developed algorithm's performance metrics, including Dice Co-efficient, Sensitivity, and Specificity, were 92.35, 90.26, and 92.42%, respectively. The Orthopedicians ascertained the efficacy of the outcomes rendered by the proposed algorithm. [ABSTRACT FROM AUTHOR]

Background: Previous studies have primarily focused on the links between fine particulate matter (PM2.5) and bone health among the general population instead of PM2.5 components and the specific population. We aimed to investigate the associations between PM2.5 components and bone health among middle-aged and elderly women. Methods: A total of 748 middle-aged and elderly women were randomly sampled from 32 streets/villages in Hubei Province. The concentrations of ambient PM2.5 and its components were extracted across various residential areas from the Tracking Air Pollution in China (TAP) dataset. Bone mineral density measurements were obtained from dual-energy X-ray absorptiometry scans of study participants. Multivariable logistic and linear models were employed to assess the relationship between PM2.5 and its components and bone loss. Results: Per interquartile range (IQR) increase in nitrate (NO3−) and ammonium (NH4+) concentrations were associated with 1.65 [95% confidence intervals (CI): 1.13, 2.30] and 1.77 (95% CI: 1.26, 2.49) times higher odds of osteoporosis, respectively. Long-term exposure to sulfate (SO42−), NO3−, and NH4+ was negatively associated with T-scores and bone mineral density in L1-L4 lumbar vertebrae. In addition, the elderly, women who have experienced menarche after the age of 14, and postmenopausal women were more susceptible to the water-soluble inorganic salts of PM2.5. Conclusion: The study emphasizes the need for comprehensive policies addressing air quality, with a specific focus on vulnerable populations such as middle-aged and elderly women. Public health interventions aimed at reducing ambient PM2.5 concentrations and minimizing exposure to its harmful components are crucial in mitigating the adverse impact on skeletal health and improving the overall well-being of communities. [ABSTRACT FROM AUTHOR]

The Trabecular Bone Score (TBS), a gray-level textural assessment derived from dual-energy X-ray absorptiometry images, serves as a validated index of trabecular bone microarchitecture. Over the past decade, significant evidence has highlighted the usefulness of TBS in primary and secondary osteoporosis, leading to its integration with the Fracture Risk Assessment Tool (FRAX) and bone mineral density (BMD) T-score adjustments. This review explores the role of TBS in fracture prediction, treatment initiation, and monitoring. Studies confirm that TBS enhances fracture risk prediction in both primary and secondary osteoporosis when combined with BMD and clinical risk factors. Evidence also suggests that including TBS alongside BMD and FRAX offers significant potential for treatment stratification, considering the overall skeletal profile, such as bone mass, bone quality, and clinical risk factors. Consequently, TBS has become a standard part of clinical care worldwide. Future enhancements hope to adjust for soft tissue thickness, broadening the applicability of TBS across diverse body types and pediatric populations. [ABSTRACT FROM AUTHOR]

Opportunistic screening uses existing imaging studies for additional diagnostic insights without imposing further burden on patients. We explore the potential of opportunistic computed tomography (CT) screening for osteoporosis, a condition affecting 500 million people globally and leading to significant health care costs and fragility fractures. Although dual-energy X-ray absorptiometry (DXA) remains the gold standard for diagnosing osteoporosis, > 50% of fractures occur in individuals not screened previously with DXA. With recent advancements in technology, CT has emerged as the most promising tool for opportunistic screening due to its wide use and the ability to provide quantitative measurements of bone attenuation, a surrogate of bone mineral density. This article discusses the technical considerations, calibration methods, and potential benefits of CT for osteoporosis screening. It also explores the role of automation, supervised and unsupervised, in streamlining the diagnostic process, improving accuracy, and potentially developing new biomarkers of bone health. The potential addition of radiomics and genomics is also highlighted, showcasing the synergy between genetic and imaging data for a more comprehensive understanding of osteoporosis pathophysiology and with it possible novel osteoporosis therapies. The future of opportunistic CT screening holds significant promise, with automation and advanced image processing ultimately enhancing patient care, reducing rates of osteoporotic fractures, and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Body composition is now recognized to have a major impact on health and disease. Imaging enables its analysis in an objective and quantitative way through diverse techniques such as dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging, and ultrasonography. This review article first surveys the methodological aspects underpinning the use of these modalities to assess body composition, highlighting their strengths and limitations as well as the set of parameters that they measure and their clinical relevance. It then provides an update on the main applications of body composition imaging in current practice, with a focus on sarcopenia, obesity, lipodystrophies, cancer, and critical care. We conclude by considering the emerging role of artificial intelligence in the analysis of body composition, enabling the extraction of numerous metrics with the potential to refine prognostication and management across a number of pathologies, paving the way toward personalized medicine. [ABSTRACT FROM AUTHOR]

Dual-energy X-ray absorptiometry (DXA) and bone mineral density (BMD) pose several limitations in some patient categories, such as pregnant women and young people. This review article explores whether the innovative radiofrequency echographic multi-spectrometry (REMS) technology is beneficial for assessing the bone condition of various patient groups. Common consequences in patients with acromegalia, prostate cancer undergoing hormone therapy, osteogenesis imperfecta, anorexia nervosa, and in a peritoneal dialysis setting include decreased BMD and an increased risk of fragility fracture. DXA is currently regarded as the gold standard for BMD assessment. However, using the DXA technique has several drawbacks in a young patient who requires repeated BMD tests because it uses ionizing radiation. Because of its precision and consistency, the REMS technique may be a valuable tool to assess changes in bone condition in patients of all ages, particularly in female patients who are fertile or who are pregnant or nursing. [ABSTRACT FROM AUTHOR]

Metabolic bone diseases (MBDs), including osteoporosis, osteomalacia, and Paget's disease, represent a significant challenge in medical imaging and intervention. Interventional radiologists play a pivotal role in managing these conditions, due to the crucial role of detailed and precise imaging in diagnosing and treating MBDs. This article offers comprehensive recommendations aimed at optimizing interventional radiologic practices for patients with MBDs, highlighting the importance of using advanced imaging modalities, including dual-energy X-ray absorptiometry and magnetic resonance imaging, essential for accurate assessment of bone mineral density and architecture, guiding effective intervention strategies. We also discuss the use of minimally invasive procedures like vertebroplasty and biopsy, vital for both diagnostic and therapeutic purposes, to enhance diagnostic accuracy and therapeutic outcomes, ensuring high-quality patient management in the context of MBDs. [ABSTRACT FROM AUTHOR]

Since its introduction in 1987, dual-energy X-ray absorptiometry (DXA) has revolutionized bone assessment, becoming the gold standard for measuring bone mineral density (BMD). Its low radiation exposure and high accuracy have made it indispensable in diagnosing osteoporosis, aligning with World Health Organization criteria. However, DXA evolution extends beyond BMD measurement, with emerging tools like the Trabecular Bone Score (TBS) and the DXA-based Bone Strain Index (BSI). TBS provides insights into trabecular bone architecture, enhancing the prediction of fracture risk. Despite limitations like body mass index correlation, TBS aids in evaluating patients with conditions such as diabetes and glucocorticoid exposure. BSI, introduced in 2019, evaluates bone strength using finite element analysis, complementing BMD and TBS by assessing bone fatigue. Advancements in DXA-based tools extend to Hip Structural Analysis and three-dimensional DXA software, offering valuable insights into hip fracture risk. Moreover, DXA serves beyond bone assessment, aiding in abdominal aortic calcification assessment, enhancing cardiovascular risk stratification. In summary, the expanding capabilities of DXA promise comprehensive skeletal and cardiovascular health evaluation, contributing significantly to clinical management and prevention strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Changes in muscle mass and bone density are common in multiple myeloma (MM) patients. Dual-energy X-ray absorptiometry (DXA) offers precise, non-invasive insights into a patient's physical condition before autologous stem cell transplantation (autoHSCT). This study examines how pre-transplant body composition impacts treatment outcomes and early complications in MM patients undergoing autoHSCT. Methods: This study is a single-center, retrospective analysis of patients with MM who were treated with first or second autoHSCT and underwent DXA pre-transplant between 11 August 2019 and 12 June 2024. Results: We conducted a study of pre-transplant body composition in 127 patients with MM. Among them, 108 (85%) qualified for first autoHSCT, while 19 (15%) qualified for a second. The median age of the patients was 64 years (range 50–73). In the Cox proportional hazards regression conducted in the group of women, Total Body %Fat was a statistically significant predictor for progression-free survival (PFS) (HR = 0.07, 95% CI = 0.01,0.6, p = 0.0157). In the Mann–Whitney U test conducted on males, Lean Mass/Height2 and Appen. Lean Height2 were statistically significant predictors of early infections after autoHSCT (Z = 1.98, p = 0.0473 and Z = 2.32, p = 0.0204, respectively). In males, Fat Mass/Height2 was a significant predictor of non-infectious toxicity related to treatment (Z = −1.98, p = 0.0476). Conclusions: In women, higher levels of adipose tissue initially appear to exert a protective effect; however, this benefit diminishes over time, with greater fat mass eventually correlating with an increased risk of disease progression. In men, muscle mass has been identified as a significant predictor of early infection risk post-autoHSCT. Furthermore, our findings indicate that an increased amount of adipose tissue in men is statistically associated with a higher risk of non-infectious treatment-related toxicity. These conclusions highlight the critical need for further investigation into the role of body composition. [ABSTRACT FROM AUTHOR]

Objectives: modulation of gut microbiota by probiotics has been proposed as a target for intervention to reduce bone mineral density (BMD) loss in the postmenopausal period. This study aims to evaluate the effect of Lacticaseibacillus (L.) paracasei LPC100 and Lactiplantibacillus (L.) plantarum LP140 on BMD in postmenopausal women in a multicenter, randomized, double-blind, placebo-controlled trial. Methods: the primary outcome was the change in T-score of the lumbar spine measured by dual-energy X-ray absorptiometry assessed after twelve-month probiotic supplementation. Secondary outcomes included changes in serological markers of inflammation and calcium–phosphate metabolism, body mass index, gastrointestinal symptoms, and satisfaction with the intervention. Results: a decrease in T-score indicating the progressive bone demineralization reached a statistically significant difference in the placebo group (from mean values of 0.06 ± 1.04 to −0.28 ± 1.12, p = 0.041) but not in the probiotic group (0.19 ± 0.99 and −0.08 ± 1.05, respectively, p = 0.125) with a p-value = 0.089 between the groups. No significant differences were found in secondary outcomes with the exception of vitamin D concentration and a significant reduction in some gastrointestinal symptoms in the probiotic group. A significant decrease in vitamin D level was observed only in the placebo group (p = 0.014). Probiotics were safe and well tolerated. Conclusions: this study suggests that the oral administration of L. paracasei LPC100 and L. plantarum LP140 may be a viable strategy to prevent BMD loss and vitamin D deficiency in postmenopausal women, but further research is necessary to confirm clinical benefits and to know the mechanism of action [ClinicalTrial.gov NCT06375668]. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis bone disease (CFBD) is a common comorbidity in adult people with cystic fibrosis (pwCF), resulting in an increased risk of bone fractures. This study evaluated the capacity of artificial intelligence (AI)-assisted low-dose chest CT (LDCT) opportunistic screening for detecting low bone mineral density (BMD) in adult pwCF. Methods: In this retrospective single-center study, 65 adult pwCF (mean age 30.1 ± 7.5 years) underwent dual-energy X-ray absorptiometry (DXA) of the lumbar vertebrae L1 to L4 to determine BMD and corresponding z-scores and completed LDCTs of the chest within three months as part of routine clinical care. A fully automated CT-based AI algorithm measured the attenuation values (Hounsfield units [HU]) of the thoracic vertebrae Th9–Th12 and first lumbar vertebra L1. The ability of the algorithm to diagnose CFBD was assessed using receiver operating characteristic (ROC) curves. Results: HU values of Th9 to L1 and DXA-derived BMD and the corresponding z-scores of L1 to L4 showed a strong correlation (all p < 0.05). The area under the curve (AUC) for diagnosing low BMD was highest for L1 (0.796; p = 0.001) and Th11 (0.835; p < 0.001), resulting in a specificity of 84.9% at a sensitivity level of 75%. The HU threshold values for distinguishing normal from low BMD were <197 (L1) and <212 (Th11), respectively. Conclusions: Routine LDCT of the chest with the fully automated AI-guided determination of thoracic and lumbar vertebral attenuation values is a valuable tool for predicting low BMD in adult pwCF, with the best results for Th11 and L1. However, further studies are required to define clear threshold values. [ABSTRACT FROM AUTHOR]

Changes in body composition often accompany the progression of liver disease and seem to be an aggravating pathophysiological factor. Specifically, accelerated loss of skeletal muscle mass, lower muscle quality, and changes in body fat distribution have been shown to be associated with poor clinical outcomes. The aim of the present narrative review was to discuss the current status and relevance of commonly applied, advanced, non-invasive methods to quantify skeletal muscle mass, muscle fat infiltration—i.e., myosteatosis—and fat distribution. This review focuses in particular on Computed Tomography (CT), Dual-energy X-ray Absorptiometry (DXA), Bioelectrical Impedance Analysis (BIA), Magnetic Resonance Imaging (MRI), and Ultrasonography (US). We propose future directions to enhance the diagnostic and prognostic relevance of using these methods for quantitative body composition assessment in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. Results: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function. [ABSTRACT FROM AUTHOR]

Study Design. Retrospective cross-sectional. Objectives. To determine associations between Hounsfield units (HU) within a region of interest on computed tomography (CT) scans and dual energy X-ray absorptiometry (DEXA) measurements in children and adolescents. Summary of Background Data. HU on CT scans as a proxy for bone mineral density (BMD) is widely used in adults. However, the utility of CT as a proxy for BMD have not been evaluated in children and adolescents. Materials and Methods. Patients younger than 18 years with a lumbar spine CT scan and a DEXA within 6 months of each other were identified. A region of interest was used to measure the HU at each lumbar vertebral body on midaxial cuts. Charts were reviewed for demographics, medical comorbidities, and DEXA reports. Correlation coefficients were calculated between the mean DEXA Z-score and the HU value. Patients were also stratified by Z-score (= -1.0, between -1.0 and -2.0, and =-2.0) and matched by age, sex and body mass index (BMI) to a cohort of healthy children and compared. Results. A moderate correlation between mean DEXA Z-score and mean HU on CT was found (r2=0.42, P< 0.001). After matching for age, sex and BMI, 21 patients in each group between the ages of 4 and 17 years were analyzed. The mean HU value of the control group was 231.69. When stratified by Z-score (= -1.0, between -1.0 and -2.0, and =-2.0), the mean HU values were 244.59, 216.50, and 176.54, respectively. Patients with a Z-score of =-2.0 had a significantly lower mean HU than matched controls. Conclusions. HU on lumbar CT in children and adolescents with DEXA Z-scores <-2.0, were lower when compared with healthy matched controls. This study suggests that HU on opportunistic CT scans of the spine may be used as a reasonable proxy for BMD in the pediatric population. [ABSTRACT FROM AUTHOR]

Bone quality in the pedicle region generally determines screw pullout strength, insertion torque, and vertebral body loading characteristics. Dual-energy X-ray absorptiometry (DEXA), as the gold standard for evaluating bone mineral density (BMD), cannot measure the BMD of specific parts, such as pedicle, and DEXA is limited in many ways. Recent studies have shown a correlation between the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score and BMD measured using DEXA or quantitative computed tomography (QCT). However, no studies have been reported on the MRI-based pedicle bone quality (PBQ) score. Moreover, few studies have investigated the relationship between MRI-based PBQ and osteoporosis. To create a new site-specific MRI-based PBQ assessment method and assess its diagnostic capacity in patients with normal BMD and osteopenia/osteoporosis. A retrospective study. A total of 156 patients underwent lumbar fusion surgery for chronic low back pain at our hospital between 2021 and 2022, with lumbar QCT and T1-weighted MRI performed before surgery. Correlation of the PBQ score with QCT BMD, and the association between the PBQ score and presence of osteopenia/osteoporosis. BMD of the lumbar was calculated as the mean BMD of the L1 and L2 vertebral bodies on the basis of asynchronous QCT measurements. The PBQ score, which is the average of the bone quality values of both pedicles on the basis of site-specific T1-weighted sagittal MRI images, was calculated by dividing the median signal intensity of the L1–L4 pedicles by the signal intensity of the cerebrospinal fluid at the L3 level. The interobserver reliability of the PBQ score was assessed using the intraclass correlation coefficient (ICC). A receiver operating characteristic curve was drawn, and the area under the curve (AUC) was calculated to assess the predictive performance of PBQ for osteoporosis. The PBQ score was compared with QCT BMD, as the gold standard, using Pearson correlation analysis. In total, 156 patients participated in this study, including 51 in the Normal BMD group and 105 in the osteopenia/osteoporosis group. The PBQ score in the osteopenia/osteoporosis group was significantly higher than that in the normal BMD group (3.19±0.55 vs 2.84±0.51, p<.001). The VBQ and PBQ scores were calculated by 2 authors and were in good agreement (intraclass correlation coefficient=0.949 and 0.929, respectively). Pearson's test showed a significant negative correlation between PBQ and QCT BMD (r=−0.4887, p<.001). The optimal cutoff PBQ score to differentiate patients with osteopenia/osteoporosis from those with normal BMD was 3.160, with a sensitivity of 66.7%, specificity of 72.5%, and AUC of 0.776. The PBQ score correlated more strongly with QCT BMD (r=−0.4887) than VBQ (r=−0.4078). In this study, we propose a novel, MRI-based pedicle-specific bone quality score. This is the first study to investigate the relationship between the PBQ score and QCT BMD. The PBQ score showed diagnostic utility, differentiating between patients with osteopenia/osteoporosis and those with normal BMD (AUC=0.776), and the PBQ score correlated more strongly with QCT BMD than VBQ. [ABSTRACT FROM AUTHOR]

To tackle the burden of obesity-induced cardiometabolic disease, the scientific community relies on accurate and reproducible adiposity measurements in the clinic. These measurements guide our understanding of underlying biological mechanisms and clinical outcomes of human trials. However, measuring adiposity and adipose tissue distribution in a clinical setting can be challenging, and different measurement methods pose important limitations. BMI is a simple and high-throughput measurement, but it is associated relatively poorly with clinical outcomes when compared with waist-to-hip and sagittal abdominal diameter measurements. Body composition measurements by dual energy X-ray absorptiometry or MRI scans would be ideal due to their high accuracy, but are not high-throughput. Another important consideration is that adiposity measurements vary between men and women, between adults and children, and between people of different ethnic backgrounds. In this Perspective article, we discuss how these critical challenges can affect our interpretation of research data in the field of obesity and the design and implementation of clinical guidelines. Accurate measurement of adiposity and adipose tissue distribution is essential for the treatment of obesity and cardiometabolic disease, but can often prove challenging. This Perspective discusses the advantages and disadvantages of different methods of assessing adiposity in clinical settings. [ABSTRACT FROM AUTHOR]

This study examined the relationship between body composition and on-field, in-game physical performance in female collegiate soccer players. Body composition, including total mass, fat mass, and lean tissue mass for the lower extremities and total body, was measured in 10 starting players using dual energy x-ray absorptiometry (DXA). On-field, in-game physical performance was tracked via a global positioning system (GPS) over 14 regular-season games, measuring total distance and distance covered in six speed zones. Players covered 4544.7 ± 495.2 m in the first half of the game and significantly less distance in the second half (3356.5 ± 1211.7 m, p = 0.004). A repeated measures ANOVA revealed decreased distances in jogging, low-, and moderate-intensity running during the second half compared to the first half of the game (p < 0.001). Lower total-body fat mass, total-body fat percentage, and lower-extremities fat mass were correlated with greater distances at moderate- and high-intensity running during the second half and entire game (r values from −0.644 to −0.745, p < 0.01 to 0.04). These findings suggest that body composition can influence the distance covered at moderate- and high-intensity running speed during competitive games. Training strategies aimed at reducing fat mass and incorporating high-intensity training may benefit female soccer players and enhance team success. [ABSTRACT FROM AUTHOR]

This article provides information on osteoporosis management in primary care. Osteoporosis is a skeletal disease characterized by low bone mass and increased fracture risk. In the UK, approximately 5.2% of the population is affected, with fragility fractures impacting individuals' quality of life and mortality rates. The approach to treatment has shifted towards assessing fracture risk rather than relying solely on bone mineral density readings. The article discusses fracture risk assessment, drug treatments available, and when referral to specialist care may be necessary. It also provides guidance on the duration of treatment and the importance of regular review and monitoring. [Extracted from the article]

Background: The adult human skeleton is composed of cortical and cancellous bone. The proportions of these two types of bone tissue differ in various parts of the skeleton. The aim of this cross-sectional study was to quantify the determinants of bone mineral density (BMD) and bone mineral content in various regions of interest (ROIs) in smokers and never-smokers. Methods: In this study, 4,332 bone scans of three regions of interest (ROIs) were analyzed: the forearm (distal and proximal), femur, and lumbar spine. Body composition and bone parameters were measured using dual-energy X-ray absorptiometry. Smoking was measured using the Global Adult Tobacco Survey questionnaire. Body mass index (BMI) was calculated, and physical activity (PA) was characterized by the metabolic equivalent of task (MET). Results: Among women, the interaction between PA (positive ß coefficient) and smoking (negative ß coefficient) was a significant predictor of BMD in the distal and proximal forearm (adj. R2 = 0.40 and R2 = 0.58; p < 0.001). The interaction of three variables--age, smoking (negative ß), and MET (positive ß)--was significant for total hip BMD (adj. R2 = 0.54; p < 0.001). The interaction between BMI and MET (positive ß) and smoking (negative ß) was significant for BMD in the lumbar spine (adj. R2 = 0.62; p < 0.001). In men, the interaction between MET (positive ß) and smoking (negative ß) was significant for BMD in the forearm and lumbar spine (adj. R2 = 0.44, R2 = 0.46, and R2 = 0.49; p < 0.01). Smoking alone was a significant negative predictor of total hip BMD (adj. R2 = 0.34; p < 0.001). Conclusion: Among both women and men, never-smokers had significantly better bone parameters than smokers. Smoking was a significant negative predictor for BMD in the various ROIs in both women and men. Physical activity was a significant positive predictor of BMD, with a strong association with bone parameters. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is the most common metabolic bone disease that begins with a decrease in bone mass and deterioration in the micro-architecture of the bone tissue, making the bones thinner and susceptible to fragility. A comprehensive estimation of the prevalence of osteoporosis in provinces of Iran seems to be necessary. Methods: This study was a descriptive-analytical study. The study population included 518 people aged 30-65 years including 297 males and 221 females to measure their bone density. The data collection method was through BMD measurement using Dual-Energy X-ray Absorptiometry (DXA) method. All obtained data stored in the SPSS-16 database and statistically analyzed. The data analyzed using analytical, statistical methods. The significance level of the test was considered to be P=0.05. Results: In the present study, according to BMI status, 45.2% of the patients were obese, 38.2% were overweight. Despite the general belief that increasing in weight can be associated with an increase in bone mass, the present research revealed that nearly 35.9% of the research population, suffered obesity and osteoporosis at the same time. Metargression analysis of data from different studies have illustrated that changing in frequency of osteoporosis as an oriented change in prevalence of osteoporosis from west to east and south to north (P=0.05) Conclusion: Iran society is under concern to more osteoporosis in the coming years at young and old ages which doubled with severe decline in growth rate of population from 3.7% to 0.63% in 2022. This can increase older people ratio over 30% in 2050. [ABSTRACT FROM AUTHOR]

Context Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. Objective To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. Design Open-label trial with 2 treatment arms. Setting Pediatric Endocrine Clinic at Stanford. Participants A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. Intervention Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. Main Outcome Measures Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. Results Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P =.043) in linear mixed models. Conclusion Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue. [ABSTRACT FROM AUTHOR]

Background: Osteo-sarcopenia (OS) has become a global public health problem and a frontier research problem, as a combination of sarcopenia (SP) and osteoporosis (OP) diseases. The clinical performances include muscle weakness, systemic bone pain, standing difficulty, even falls and fractures, etc., which seriously affect the patient's life and work. The pathological mechanism of the OS may be the abnormal metabolism which disrupts the equilibrium stability of the musculoskeletal system. Therefore, this study combined vitamin D (Vit. D) and whole-body vibration training (WBVT) to intervene in subjects of OS, aiming to evaluate the effectiveness and safety of the diagnosis and treatment protocol and to explore the efficacy mechanism. Methods: We propose a multicenter, parallel-group clinical trial to evaluate the efficacy and safety of Vit. D combined with WBVT intervention in OS. Subjects who met the inclusion or exclusion criteria and signed the informed consent form would be randomly assigned to the WBVT group, Vit. D group, or WBVT+ Vit. D group. All subjects will be treated for 1 month and followed up after 3 and 6 months. The primary outcomes are lumbar bone mineral density (BMD) and appendicular skeletal muscle mass (ASM) measured by dual-energy X-ray absorptiometry (DXA) and handgrip strength measured by grip strength meter. Secondary outcomes include serum markers of myostatin (MSTN), irisin and bone turnover markers (BTM), SARC-CalF questionnaire, 1-min test question of osteoporosis risk, patient health status (evaluated by the SF-36 health survey), physical performance measurement that includes 5-time chair stand test, 6-m walk, and the short physical performance battery (SPPB). Discussion: If Vit. D combined with WBVT can well relieve OS symptoms without adverse effects, this protocol may be a new treatment strategy for OS. After therapeutic intervention, if the serum marker MSTN/irisin is significant, both have the potential to become sensitive indicators for screening OS effective drugs and treatments, which also indicates that WBVT combined with Vit. D plays a role in improving OS by regulating MSTN/irisin. Trial registration: Chinese Clinical Trial Registry ChiCTR2400082269. Registered on March 26, 2024. [ABSTRACT FROM AUTHOR]

The advent of biobanks with vast quantities of medical imaging and paired genetic measurements creates huge opportunities for a new generation of genotype–phenotype association studies. However, disentangling biological signals from the many sources of bias and artifacts remains difficult. Using diverse medical images and time-series (ie, magnetic resonance imagings [MRIs], electrocardiograms [ECGs], and dual-energy X-ray absorptiometries [DXAs]), we show how registration, both spatial and temporal, guided by domain knowledge or learned de novo, helps uncover biological information. A multimodal autoencoder comparison framework quantifies and characterizes how registration affects the representations that unsupervised and self-supervised encoders learn. In this study we (1) train autoencoders before and after registration with nine diverse types of medical image, (2) demonstrate how neural network-based methods (VoxelMorph, DeepCycle, and DropFuse) can effectively learn registrations allowing for more flexible and efficient processing than is possible with hand-crafted registration techniques, and (3) conduct exhaustive phenotypic screening, comprised of millions of statistical tests, to quantify how registration affects the generalizability of learned representations. Genome- and phenome-wide association studies (GWAS and PheWAS) uncover significantly more associations with registered modality representations than with equivalently trained and sized representations learned from native coordinate spaces. Specifically, registered PheWAS yielded 61 more disease associations for ECGs, 53 more disease associations for cardiac MRIs, and 10 more disease associations for brain MRIs. Registration also yields significant increases in the coefficient of determination when regressing continuous phenotypes (eg, 0.36 ± 0.01 with ECGs and 0.11 ± 0.02 for DXA scans). Our findings reveal the crucial role registration plays in enhancing the characterization of physiological states across a broad range of medical imaging data types. Importantly, this finding extends to more flexible types of registration, such as the cross-modal and the circular mapping methods presented here. [ABSTRACT FROM AUTHOR]

This study aims to (1) compare the kinetics of pulmonary oxygen uptake (VO2p), skeletal muscle deoxygenation ([HHb]), and microvascular O2 delivery (QO2mv) between heart failure (HF) patients with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF), and (2) explore the correlation between body composition, kinetic parameters, and exercise performance. Twenty-one patients (10 HFpEF and 11 HFrEF) underwent cardiopulmonary exercise testing to assess VO2 kinetics, with near-infrared spectroscopy (NIRS) employed to measure [HHb]. Microvascular O2 delivery (QO2mv) was calculated using the Fick principle. Dual-energy X-ray absorptiometry (DEXA) was performed to evaluate body composition. HFrEF patients exhibited significantly slower VO2 kinetics (time constant [t]: 63 ± 10.8 s vs. 45.4 ± 7.9 s; P < 0.05) and quicker [HHb] response (t: 12.4 ± 9.9 s vs. 25 ± 11.6 s; P < 0.05). Microvascular O2 delivery (QO2mv) was higher in HFrEF patients (3.6 ± 1.2 vs. 1.7 ± 0.8; P < 0.05), who also experienced shorter time to exercise intolerance (281.6 ± 84 s vs. 405.3 ± 96 s; P < 0.05). Correlation analyses revealed a significant negative relationship between time to exercise and both QO2mv (ρ= -0.51; P < 0.05) and VO2 kinetics (ρ= -0.63). Body adiposity was negatively correlated with [HHb] amplitude (ρ= -0.78) and peak VO2 (ρ= -0.54), while a positive correlation was observed between lean muscle percentage, [HHb] amplitude, and tau (ρ= 0.74 and 0.57; P < 0.05), respectively. HFrEF patients demonstrate more severely impaired VO2p kinetics, skeletal muscle deoxygenation, and microvascular O2 delivery compared to HFpEF patients, indicating compromised peripheral function. Additionally, increased adiposity and reduced lean mass are linked to decreased oxygen diffusion capacity and impaired oxygen uptake kinetics in HFrEF patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females. Methods: A total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imagingbased MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL. Results: Simple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (b = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (b = -0.200, 95% CI -0.348 to -0.051 for vertebral BMD; b = -0.383, 95% CI -0.589 to -0.177 for total hip BMD; and b =-0.393, 95% CI -0.598 to -0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (b = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above. Conclusions: Vertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females. [ABSTRACT FROM AUTHOR]

Skeletal muscle index measurement via dual-energy X-ray absorptiometry or bioelectrical impedance analysis is used to evaluate muscle mass when diagnosing sarcopenia. However, inherent challenges exist with these methods. We previously focused on muscle mass evaluation in the quadriceps femoris by using computed tomography (CT). In this observational study, we utilized a new ultrasound device with a wide field of view that can obtain CT-like images and investigated its usefulness. Reproducibility was investigated by calculating the intra- and inter-examiner intraclass correlation coefficient (ICC) by using three examiners and performing five measurements in 12 participants. In 123 participants (48 men, 75 women, mean age 78.2 ± 8.1 years), we investigated the correlation between the quadriceps cross-sectional area measured with supine ultrasound and CT images as well as between supine and sitting ultrasound images. Unadjusted, age-adjusted, and age–sex-adjusted correlations were calculated. Reproducibility was excellent (intra-examiner ICC[1,1]: 0.978, 0.987, and 0.994; inter-examiner ICC[2,1]: 0.993). The unadjusted, age-adjusted, and age–sex-adjusted correlations between the quadriceps cross-sectional area measured using supine ultrasound and CT were 0.949, 0.940, and 0.894, respectively. For sitting ultrasound, the corresponding values were 0.958, 0.953, and 0.912, respectively. Correlations between the supine and sitting ultrasound measurements were also good, with corresponding values of 0.952, 0.945, and 0.904, respectively. The tested ultrasound device showed excellent measurement reproducibility and had good correlations with CT images. Further studies with an increased numbers of clinical cases and additional evaluations should allow the device to become a screening tool for diagnosing sarcopenia. [ABSTRACT FROM AUTHOR]

The introduction of dual-energy X-ray absorptiometry (DXA) technology in the 1980s revolutionized the diagnosis, management and monitoring of osteoporosis, providing a clinical tool which is now available worldwide. However, DXA measurements are influenced by many technical factors, including the quality control procedures for the instrument, positioning of the patient, and approach to analysis. Reporting of DXA results may be confounded by factors such as selection of reference ranges for T-scores and Z-scores, as well as inadequate knowledge of current standards for interpretation. These points are addressed at length in many international guidelines but are not always easily assimilated by practising clinicians and technicians. Our aim in this report is to identify key elements pertaining to the use of DXA in clinical practice, considering both technical and clinical aspects. Here, we discuss technical aspects of DXA procedures, approaches to interpretation and integration into clinical practice, and the use of non-bone mineral density measurements, such as a vertebral fracture assessment, in clinical risk assessment. [ABSTRACT FROM AUTHOR]

Background: A significant loss in bone density and strength occurs during the post-renal-transplant period with higher susceptibility to fracture. The study aims to compare the performance of the Radiofrequency Echographic Multi Spectrometry (REMS) in the bone mineral density assessment with the conventional dual-energy X-ray absorptiometry (DXA) in a cohort of kidney transplant recipients (KTR). Methods: A cohort of 40 patients underwent both DXA and REMS examinations on the lumbar spine and/or proximal femur. The paired t-test was used to compare DXA and REMS measurements; the chi-square test was used to compare the prevalence of osteoporosis/osteopenia. The agreement between the two techniques was assessed through Spearman's correlation. Results: As expected, most KTR patients were osteopenic or osteoporotic with both REMS and DXA (86.5% and 81% for the femur; 88% and 65% for the lumbar spine p < 0.05). A modest correlation (r = 0.4, p < 0.01) was observed at the lumbar spine between the T-score measured by REMS and DXA. A strong correlation was defined between REMS and DXA in the femoral region (r = 0.7, p < 0.0001). Conclusions: The study demonstrates the exchangeability of the two techniques on the proximal femur in KTR and a higher diagnostic accuracy of REMS at the spine level than DXA. [ABSTRACT FROM AUTHOR]

Background: In adults with Klinefelter syndrome (KS), impaired bone health with reduced bone mineral density (BMD) has been described even in the presence of testosterone replacement therapy. The aim of the present study was to characterize bone health in young patients with KS. Patients and methods: 20 participants aged 16.10 ± 4.28 years with KS (7 with testosterone replacement therapy) were included in the KliBONE study (DRKS 00024870). Medical history, clinical, radiographic and biochemical parameters of bone health and metabolism were obtained. Radiographic bone health index (BHI) was assessed via automated digital X-ray radiogrammetry of the left hand or via dual energy X-ray absorptiometry (DXA) of the lumbar spine and left femur in participants ≥ 16 years. Peripheral blood mononuclear cells were differentiated into osteoclasts and quantified in 7 participants and 7 healthy controls. Results: Mean BHI SDS was − 1.42 ± 1.22 and mean BMD z-score at the lumbar vertebrae (L1-4) was − 0.92 ± 1.00. 25-OH-vitamin D levels < 20 ng/ml were detected in 8/20. Other parameters of bone metabolism (bone-specific alkaline phosphatase, PTH, ß-crosslaps and osteocalcin) were within age-appropriate reference ranges. Serum leptin SDS was elevated (mean 2.15 ± 1.19). The number of osteoclasts in participants with KS did not differ from that of controls. Conclusion: BHI SDS and BMD z-scores were lower than expected in young individuals with KS despite age-appropriate bone turnover markers and no apparent pathology in osteoclast differentiation. The cause of the early-onset bone phenotype requires further investigation. [ABSTRACT FROM AUTHOR]

Low body mass index is closely related to a high risk of Alzheimer's disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia's association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = − 0.206, p = 0.020) and clinical outcomes (low MMSE, β = − 1.364, p = 0.025; low SVLT, β = − 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications. [ABSTRACT FROM AUTHOR]

This study addresses the pressing need for improved methods to predict lean mass in adults, and in particular lean body mass (LBM), appendicular lean mass (ALM), and appendicular skeletal muscle mass (ASMM) for the early detection and management of sarcopenia, a condition characterized by muscle loss and dysfunction. Sarcopenia presents significant health risks, especially in populations with chronic diseases like cancer and the elderly. Current assessment methods, primarily relying on Dual-energy X-ray absorptiometry (DXA) scans, lack widespread applicability, hindering timely intervention. Leveraging machine learning techniques, this research aimed to develop and validate predictive models using data from the National Health and Nutrition Examination Survey (NHANES) and the Action for Health in Diabetes (Look AHEAD) study. The models were trained on anthropometric data, demographic factors, and DXA-derived metrics to accurately estimate LBM, ALM, and ASMM normalized to weight. Results demonstrated consistent performance across various machine learning algorithms, with LassoNet, a non-linear extension of the popular LASSO method, exhibiting superior predictive accuracy. Notably, the integration of bone mineral density measurements into the models had minimal impact on predictive accuracy, suggesting potential alternatives to DXA scans for lean mass assessment in the general population. Despite the robustness of the models, limitations include the absence of outcome measures and cohorts highly vulnerable to muscle mass loss. Nonetheless, these findings hold promise for revolutionizing lean mass assessment paradigms, offering implications for chronic disease management and personalized health interventions. Future research endeavors should focus on validating these models in diverse populations and addressing clinical complexities to enhance prediction accuracy and clinical utility in managing sarcopenia. [ABSTRACT FROM AUTHOR]

Purpose: To examine the hypothesis that an increase in response of postmenopausal bone to interval walking training (IWT) depends on baseline bone mineral densities (BMDs). Methods: Two hundred and thirty-four postmenopausal women (64±5 (SD) yr) with no medication for osteoporosis performed 5-month IWT, repeating fast and slow walking at ≥70% and ~40% peak aerobic capacity, respectively, for 3 minutes each per set, ≥5 sets/day, ≥4 days/week. They were recruited from those who had performed IWT ≥6 months before participating in the study so that their physical fitness and lifestyle-related disease symptoms had almost reached a steady state at the time of their participation. We measured BMDs for the lumbar spine (LS), bilateral femoral neck (FN), and bilateral total hip (TH) by dual-energy X-ray absorptiometry (DXA) before and after the intervention. We used a multiple regression analysis to identify significant independent factors for increasing BMDs after the intervention as baseline physical characteristics, exercise intensity, and exercise time during IWT were the candidates. For any bone site where the independent factor identified was singular, we analyzed the relationship between the identified factor vs increases in BMD after the intervention (ΔBMD) by the locally weighted scatterplot smoothing (LOWESS) method. Results: Almost all subjects completed the designated protocol with minimal adverse events. We found that significant determinants for increasing BMDs were the baseline BMDs for all bone sites, as well as age and body mass index for TH (all, P<0.02). Furthermore, the LOWESS trendline between ΔBMDs vs the baseline BMDs, divided equally into 10 bins for LS and FN, respectively, showed that ΔBMD responses (Y) were attenuated as the baseline BMDs (X) increased in the lower 4 bins and then showed a flat line (Y = ~0) in the remaining higher 6 bins for LS and FN. When the lower 4 bins and the higher 6 bins of the baseline BMD were pooled, respectively, BMDs significantly increased by 1.8% and 1.0% in the lower groups for LS and FN, respectively (both, P<0.001) while not in the higher groups after the intervention (both, P>0.3). Conclusions: IWT may be of benefit with minimal adverse events to postmenopausal women, although the effects were greater in those with lower baseline BMDs. Trial registration: UMIN000047428. https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000047428#. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP) is a common finding in diabetic patients especially high-risk populations such as postmenopausal women. Sclerostin is a glycoprotein chiefly secreted by mature osteocytes and is considered a main regulator of bone formation. The C1q/TNF-Related Protein 3 (CTRP3) was found to be significantly associated with OP in postmenopausal women. The effect of type 2 diabetes mellitus (T2DM) on sclerostin and CTRP3 levels in postmenopausal women is rarely investigated. The present study aimed to assess the impact of T2DM on sclerostin and CTRP3 levels and their relation to OP in postmenopausal women. Methods: The study included 60 postmenopausal women with T2DM and 60 age-matched postmenopausal non-diabetic women. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA). Serum levels of sclerostin and CTRP3 were assessed using enzyme-linked immunosorbent assay (ELISA) technique. Results: Diabetic group expressed significantly higher serum levels of sclerostin when compared with non-diabetic group (110.0 ± 29.0 versus 51.5 ± 23.2 ng; p < 0.001). Oppositely, CTRP3 were significantly lower in the diabetic group (3.5 ± 3.5 versus 9.9 ± 3.7 ng/ml, p < 0.001). Multivariate logistic regression analysis identified HbA1c levels [OR (95% CI): 0.49 (0.26–0.93), p = 0.028], sclerotin levels [OR (95% CI): 1.06 (1.0-1.012), p = 0.041] and CTRP3 levels [OR (95%) CI: 1.64 (1.0-2.68), p = 0.047] as significant predictors of OP in diabetic patients. Conclusions: Sclerostin and CTRP3 levels are involved in OP in postmenopausal diabetic patients. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis Canada 2023 clinical practice guidelines increase the number of individuals recommended or suggested for anti-osteoporosis pharmacotherapy by refining treatment guidance for those who fell within the 2010 guidelines' moderate-risk category. Purpose: In 2023, Osteoporosis Canada updated its 2010 clinical practice guidelines based upon consideration of fracture history, 10-year major osteoporotic fracture (MOF) risk, and BMD T-score in conjunction with age. The 2023 guidelines eliminated risk categories, including the moderate-risk group that did not provide clear treatment guidance. The current study was performed to appreciate the implications of the shift from 2010 risk categories to 2023 treatment guidance. Methods: The study population consisted of 79,654 individuals age ≥ 50 years undergoing baseline DXA testing from January 1996 to March 2018. Each individual was assigned to mutually exclusive categories based on 2010 and 2023 guideline recommendations. Treatment qualification, 10-year predicted and 10-year observed MOF risk were compared. Results: Treatment reclassification under the 2023 guidelines only affected 33.8% of individuals in the 2010 moderate-risk group, with 13.0% assigned to no treatment, 14.4% to suggest treatment, and 6.4% to recommend treatment. During the mean follow-up of 7.2 years, 6364 (8.0%) individuals experienced one or more incidents of MOF. The observed 10-year cumulative incidence of MOF in the study population was 10.5% versus the predicted 10.7% (observed to predicted mean calibration ratio 0.98, 95% CI 0.96–1.00). Individuals reclassified from 2010 moderate risk to 2023 recommend treatment were at greater MOF risk than those in the 2010 moderate-risk group assigned to 2023 suggest treatment or no treatment, but at lower risk than those in the 2010 high-risk group. Conclusions: Osteoporosis Canada 2023 clinical practice guidelines affect individuals within the 2010 moderate-risk category, increasing the number for whom anti-osteoporosis pharmacotherapy is recommended or suggested. Increased treatment could reduce the population burden of osteoporotic fractures, though moderate-risk individuals now qualifying for treatment have a lower predicted and observed fracture risk than high-risk individuals recommended for treatment under the 2010 guidelines. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence indicates the importance of the interplay between skeletal muscles and lipid metabolism. Remnant cholesterol (remnant-C) is considered one of the principal residual risk factors for cardiovascular disease and metabolic disorders; however, there are limited studies on the impact of remnant-C on sarcopenia. Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 were used in this nationwide population-based study. In total, 17,408 participants were enrolled in this study. The subjects were categorized into four groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry. Results: A total of 1,791 participants (10.3%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.2%; Q2, 8.7%; Q3, 11.5%; Q4, 15.7%). In the full adjusted model, those in the highest remnant-C quartile group showed significantly increased odds ratio (OR) for low muscle mass compared with those in the lowest remnant-C group after adjusting for various confounding factors (OR = 1.33, 95% confidence interval (CI) = 1.06-1.68, P <0.05). A wide range of subgroups and sensitivity analyses showed consistent results, supporting the robustness of our findings. Conclusions: Increased remnant-C value was associated with a high risk of low muscle mass in the Korean population. Remnant-C may be a novel marker for the prediction and management of sarcopenia in aging societies. [ABSTRACT FROM AUTHOR]