Sex differences in musculoskeletal aging are often attributed to gonadal hormones, but the independent role of sex chromosomes remains unclear. Using the Four Core Genotype mouse model, which dissociates sex chromosomes (XX vs. XY) from gonadal sex (ovaries vs. testes), our goal was to examine sex chromosomes and gonads independent and interactive effects on bone, muscle and organ phenotypes from 8 to 20months of age in XXO, XYO, XXT, and XYT mice. XYO mice showed high mortality (38.7%-survival by 20months) when compared with other genotypes (67-86.7%). Between 8 and 20months, XYO mice showed increases in lean mass and femoral BMD and improved bone structural parameters, yet lower cortical tissue mineral density. XXO mice displayed pronounced late-life gains in body weight, lean and fat mass not observed in other genotypes, although lean mass differed only versus XXT mice at 20months. Total and spine BMD declined in XXO mice, accompanied with lower structural parameters and higher tissue mineral density than XYO mice. XXT mice displayed bone loss at all skeletal sites, whereas XYT mice showed a selective decline in spine BMD. Overall, chromosome sex adversely affected bone and muscle mass in XX versus XY mice, while gonadal sex influenced bone structure and absolute muscle mass, with mice bearing ovaries generally exhibiting lower muscle mass. Organ weight effects were modest and limited to spleen (XYO>XXO/XYT) and brain (XYT>XXT). Collectively, these findings reveal a previously unrecognized, tissue-specific contribution of sex chromosomes to musculoskeletal aging, independent of gonadal sex.

The association between cancer history and long-term body composition based on a 10-year follow-up.

Assessing the accuracy of bioelectrical impedance analysis for fat-free mass estimation in growing pigs using dual-energy X-ray absorptiometry as a reference method.

Mitigating loss of lean muscle in GLP-1 and dual GLP-1/GIP agonists: Pipeline opportunities and limitations.

Growth differentiation factor 15 (GDF15) is a protein that is produced by senescent cells during the aging process. Its level in blood increases with age and is associated with an increased risk of several age-related diseases and mortality. We measured GDF15 level in serum archived 1174 men and women aged between 70 and 79yr in the Health Aging and Body Composition study who had measurements of BMD of the hip, markers of bone turnover (PINP and CTX) and tested for several physical functions (6m gait speed, standing balance and grip strength, BMI, and appendicular lean mass) and falls, and were followed-up for incident fracture. Cox proportional hazard models were used to estimate hip fracture risk by increasing GDF15 quartiles. The mean GDF15 was significantly higher in men than in women (p < .0001) and the level significantly increased with age, slower gait speed, lower standing balance test time, and lower handgrip strength. During 11.5 (SD 4.5)yr of follow-up, 93 (8%) of the participants suffered a hip fracture and the risk was higher among women (p < .015), associated with older age, lower BMI, lower FN and TH BMD, lower appendicular lean mass, and weaker grip strength. In the unadjusted hazard model participants in the highest quartile of GDF15 had a 2-fold increased hip fracture risk (HR 2.12, p < .014) that remained significant after adjustment for age and sex (p < .037). However, the association was no longer statistically significant after adjusting for grip strength (HR 1.8, 95% CI: 0.97-3.34; p < .06). In conclusion, increased GDF15 is a predictor of hip fractures. This relationship might be partially mediated by muscle function and low lean mass but not BMD.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, and excess adiposity is a major contributor to cardiovascular (CV) risk. However, obesity is a heterogeneous condition, and body mass index (BMI) alone fails to capture important differences in fat distribution and lean mass that substantially influence CV outcomes. Growing clinical and epidemiological evidence indicates that body composition, rather than body weight per se, provides a more accurate and biologically meaningful framework for CV risk assessment. This narrative review summarizes clinical evidence linking key components of body composition, including total and regional adiposity, skeletal muscle mass, and ectopic fat depots, to CV risk and prognosis. Central and visceral adiposity are consistently shown to be more strongly associated with cardiometabolic dysfunction, atherosclerosis, and CV events than generalized obesity. In parallel, reduced lean mass and sarcopenia emerge as independent predictors of adverse CV outcomes, particularly in older adults and patients with established CVD. Ectopic fat depots, such as epicardial and hepatic fat, further contribute to CV pathology through local and systemic mechanisms. Collectively, these findings highlight the limitations of BMI-centered approaches and support the integration of body composition measures into CV risk stratification. Emphasizing body recomposition, with reduction of harmful fat depots and preservation of skeletal muscle, may enable more precise, individualized strategies for CV prevention and management.

A lipidomics approach identifies the lipid classes modulated in response to hepatic steatosis in obese fa/fa rats relative to lean Zucker rats.

Sarcopenia and sarcopenic obesity may increase surgical complications and impact recovery and function after total joint arthroplasty (TJA). We assessed the feasibility of identifying these conditions in an orthopedic practice setting using published consensus criteria. Patients in a lower extremity TJA clinic were assessed for sarcopenia and sarcopenic obesity using EWGSOP2 and ESPEN/EASO diagnostic frameworks, respectively. Low strength testing involved maximal handgrip strength (HGS) and number of chair sit-to-stands in 30 seconds (CSTS). Same day dual-energy x-ray absorptiometry (DXA) testing was used to assess for low muscle mass (i.e. appendicular lean soft tissue) in patients with low strength. One hundred-one of a possible 128 patients were assessed in clinic (93% male, mean age 69.6±8.9 years and BMI 31.7±7.9 kg/m2). HGS was completed in 99% of screened patients; only 44.5% completed CSTS due to joint pain and balance limitations. Thirty-nine patients had low strength and were recommended for DXA. In 16 patients who completed DXA, 3 had sarcopenia and 5 had sarcopenic obesity. Screening for sarcopenia and sarcopenic obesity was challenging to complete in all patients during routine clinic flow with dedicated personnel. Despite our pragmatic approach and limited screening completion in all patients, we identified sarcopenic and sarcopenic obesity in 6.25% of patients. This is likely a lower bound for the true prevalence but suggests an opportunity to assess and intervene for these conditions before surgery to improve total joint arthroplasty outcomes.

Agreement and systematic difference between bioelectrical impedance analysis and dual-energy X-ray absorptiometry for appendicular lean mass in 1617 community-dwelling older adults: The Bunkyo Health Study.

Real-world effectiveness of oral semaglutide on body weight, composition, and metabolic parameters in patients with obesity without diabetes.

To evaluate the cost-effectiveness of opportunistic CT for sarcopenia screening compared with standard-of-care clinical screening methods, using a decision-analytic model based on quality-adjusted life years (QALYs) and healthcare costs. We developed a decision-analytic model simulating a hypothetical cohort of 70-year-old male patients at risk for sarcopenia over a 3-year time horizon from a US healthcare system perspective. The model compared two screening strategies: standard-of-care clinical evaluation per EWGSOP2 guidelines (physical exam + DXA evaluation of lean mass) and opportunistic CT as measures of muscle mass and quality. Model inputs-including screening sensitivities/specificities, costs, utility values, and probabilities of cardiovascular complications-were derived from published literature. Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated, and sensitivity analyses were performed to assess the robustness of findings across variable inputs. Opportunistic CT was the favored strategy, with lower costs ($845 vs. $1,295), comparable effectiveness (0.87 QALYs), and higher net monetary benefit ($86,037 vs. $85,588) relative to the standard-of-care strategy. The standard-of-care strategy's ICER was $47.7 million per QALY, exceeding our willingness-to-pay threshold of $100,000. Probabilistic sensitivity analysis across 100,000 simulations demonstrated that opportunistic CT was favored across all tested willingness-to-pay thresholds up to $200,000. Opportunistic CT is a cost-effective strategy for sarcopenia screening, offering similar effectiveness at a lower cost compared to the standard-of-care approach. By leveraging existing imaging studies, opportunistic CT screening has the potential to enhance early detection and decrease the underdiagnosis of sarcopenia while also reducing the burden of additional DXA scans and clinical visits.

Myostatin negatively regulates skeletal muscle size in multiple species, and therefore, myostatin blockade has been therapeutically explored to promote muscle growth in humans, including to counter the muscle loss seen in obese humans using GLP1R agonists. In this study, we present results from a large multi-cohort genetic association analysis, using data from 1.1 million individuals to examine the effects of function-disrupting mutations in the myostatin gene (MSTN) on traits relevant to body composition and cardiometabolic health. Carriers of function-disrupting variants display decreased adiposity, an increase in lean mass, and increased grip strength and creatinine levels. We further characterize the effects of these variants on body composition using whole-body MRI data from UK Biobank, leveraging deep learning models to perform automated image segmentation for 77,572 individuals. Among mutation carriers increased muscle mass is observed across multiple muscle groups, with heterozygote carriers of loss-of-function-like mutations exhibiting increases in excess of 10%. Our findings demonstrate that lifelong reduction in myostatin function enhances muscle size and strength in humans while decreasing body adiposity, providing insights into the potential benefits and safety of long-term therapeutic blockade of myostatin signaling.

This study aimed to investigate the characteristics of body composition, core symptoms, functional impairment, and comorbidities in children with attention-deficit hyperactivity disorder (ADHD) and sarcopenia. A case-control study compared children with ADHD and sarcopenia (n = 85) with matched ADHD-only controls (n = 85). Comprehensive evaluations included body composition analysis and standardized behavioral assessments (SNAP-IV, Vanderbilt, WFIRS). Compared to the control group, the ADHD with sarcopenia group exhibited significantly lower values on total body water, protein, minerals, body fat mass, fat-free mass, bone mineral content, body mass index, fat mass index, and fat-free mass index (False Discovery Rate (FDR) corrected P < 0.05), while exhibiting higher muscle-to-fat ratio. They also demonstrated lower ADHD core symptom severity, decreased comorbidity proportion (including oppositional defiant disorder [ODD]), and impaired family function (FDR corrected P < 0.05). Regression analysis identified hyperactive-impulsive symptom severity (OR 3.97, 95% CI:2.22-7.12) and increased soft lean mass (SLM) (OR 1.13, 95% CI:1.05-1.21) as predictors of comorbid ODD risk. ADHD children with sarcopenia had lower body composition values, milder core symptoms, and fewer comorbidities (including ODD). SLM and hyperactive-impulsive symptoms exhibited positive associations with comorbid ODD risk in children with ADHD. Children with ADHD and sarcopenia show skeletal muscle wasting alongside declines in fat mass, protein content, and bone mineral content compared with the control group (children with ADHD without sarcopenia). The ADHD-sarcopenia group (participants with both ADHD and sarcopenia) had significantly lower ADHD core symptom scores (inattention and hyperactivity-impulsivity) and a reduced comorbidity proportion. Hyperactivity-impulsivity symptoms and soft lean mass increased the risk of comorbid oppositional defiant disorder in children with ADHD.

As neonatal care continues to evolve, there is growing recognition of the need for individualized, functionally targeted nutrition in very preterm infants (VPIs). While human milk remains the gold standard, it frequently fails to meet the metabolic requirements of this high-risk group, requiring the adoption of fortification strategies. In this context, the study by Rasmussen et al., published in Pediatric Research, offers important insights into the metabolic implications of fortifying human milk with bovine colostrum (BC). The observed elevations in plasma concentrations of amino acids such as arginine, glutamine, and tyrosine suggest that BC may serve as a fortifier with potential clinical value. However, the disconnection between enhanced biochemical profiles and clear clinical benefit persists. Nutrient utilization depends not only on intake but also on inflammation, illness, organ immaturity, and individual metabolic variations. Infants' anthropometrics, mainly head circumference and length, remain essential reference values, mirroring brain and lean mass development. A shift toward precision strategies incorporating biomarkers and long-term developmental follow-up is needed. This approach might hopefully be translated into sustained clinical benefit for VPIs. IMPACT: This commentary emphasizes the importance of evaluating neonatal nutrition through both surrogate biomarkers and functional clinical outcomes to better capture physiological relevance. It highlights the limitations of relying exclusively on compositional or biochemical analyses when assessing nutritional adequacy in preterm infants. The article contextualizes the findings of Rasmussen et al. within the metabolic complexity characteristic of preterm physiology. It underscores the role of clinical heterogeneity and variable nutrient utilization in shaping metabolic responses. The commentary advocates for integrated, technology-supported strategies to enable individualized, real-time precision nutrition in neonatal care.

Osteosarcopenia is a major public health concern, but its association with mortality, remains understudied. We aimed to examine the associations between osteoporosis, sarcopenia, and osteosarcopenia with mortality. We used two populations: the Manitoba Bone Mineral Density Database (MBMDD) study (1999-2018) and the National Health and Nutrition Examination Survey (NHANES) study (2001-2019). Individuals aged 50 years or above with complete data on BMD, appendicular lean body mass, demographic characteristics and comorbidity measures. Five definitions for diagnosis of SP were considered: Foundation for the National Institutes of Health (FNIH1, FNIH2); European Working Group on Sarcopenia in Older People (EWGSOP2); Asian Working Group for Sarcopenia (AWGS); International Working Group on Sarcopenia (IWG). Disease was classified as follows: osteoporosis only (individuals with osteoporosis alone), sarcopenia only (individuals with sarcopenia alone), osteosarcopenia (individuals with both osteoporosis and sarcopenia). The main outcome was all-cause mortality. The MBMDD and NHANES included 69,497 (90.8% females) and 8134 (52.1% females), respectively. The average ages were 65.6±9.5 years in the MBMDD cohort and 59.1±8.5 years in the NHANES. Mortality was significantly higher in those with osteoporosis (MBMDD: hazard ratio [HR]: 1.26, 95%confidence interval [CI]: 1.21-1.32; NHANES: HR: 1.31, 95%CI: 1.07-1.60), sarcopenia (EWGSOP2: MBMDD: HR: 1.64, 95%CI: 1.52-1.78; NHANES: HR: 1.45, 95%CI: 1.30-1.62) and osteosarcopenia (EWGSOP2: MBMDD: HR: 2.05, 95%CI: 1.91-2.19; NHANES: HR: 1.91, 95%CI: 1.45-2.52). In summary, osteoporosis, sarcopenia and osteosarcopenia were all significantly associated with increased mortality risk. Osteosarcopenia exhibited a stronger association with mortality than either osteoporosis or sarcopenia alone.

Weight/fat mass gain to support resumption of normal menses can be an important treatment goal for female athletes with amenorrhoea (AMEN) or oligomenorrhoea (OLIGO) related to relative energy deficiency in sport (REDs). However, targets based on body mass index (BMI) or per cent expected body weight (%EBW) may be less applicable in athletes, who typically have greater lean mass compared with the general population. Our aim was to determine if dual-energy X-ray absorptiometry (DXA)-derived %fat Z-score can detect menstrual status in female athletes and if a %fat Z-score cut-off of <-1.0 is a better indicator than standard BMI (in those >20 years) or %EBW (in those ≤20 years) thresholds. 388 female athletes (age 15-30 years, Tier ≥2) with DXA scans were classified as AMEN (n=159), OLIGO (n=84) or naturally menstruating (NM, n=145) using clinical records. We compared %fat Z-score and BMI or %EBW values across menstrual groups and calculated sensitivity and specificity for predicting AMEN and the combined OLIGO and AMEN groups (OLIGO/AMEN) using traditional BMI or %EBW risk cut-offs versus a risk cut-off of <-1.0 for %fat Z-score. %fat Z-score was superior to traditional BMI or %EBW thresholds in discriminating between menstrual status groups. Using a %fat Z-score cut-off <-1.0 improved sensitivity (p<0.0001) for predicting AMEN (68.9%) and OLIGO/AMEN (57.7%) compared with the sensitivity of traditional BMI or %EBW cut-offs for AMEN (29.3%) and OLIGO/AMEN (25.9%). However, %fat Z-score <-1.0 did not improve specificity for predicting AMEN (75.4%) nor OLIGO/AMEN (79.9%) compared with the specificity of traditional BMI or %EBW cut-offs for AMEN (83.9%; p=0.0078) and OLIGO/AMEN (85.2%; p=0.14). When attempting to resume normal menstruation, achieving a %fat Z-score ≥-1.0, rather than using BMI or %EBW targets, may be a better goal for athletes with REDs-related amenorrhoea or oligomenorrhoea.

Ayurveda prioritizes prevention and personalized treatment based on Tridosha composition. Very few studies have adopted the transdiagnostic approach of associating Tridosha with anthropometric and body composition parameters, especially in the Indian population. To map Tridosha with anthropometric somatotypes and body compositions, and develop regression models for predicting Vata, Pitta, and Kapha from physical parameters. This cross-sectional study assessed 57 healthy male Indian university students who underwent anthropometric and body composition assessments including Heath-Carter somatotyping, and Tridosha profiling (using Ayusoft®). Chi-square tests with Cramer's-V statistics evaluated associations between Tridosha, somatotype, and body mass index (BMI) categories. Least absolute shrinkage and selection operator (LASSO) regression models were developed to predict Vata, Pitta, and Kapha from physical parameters. Vata and Kapha showed significant (P < .001) negative and positive correlations, respectively, with weight, BMI, lean body mass, soft lean mass, mean body fat, body fat%, waist and hip circumference, waist-height ratio, endomorph, and mesomorph. Pitta showed a similar trend as Kapha in waist circumference, BMI, waist-height and height-weight ratio, mesomorph, and ectomorph only; however, the correlations were weak (|r| < 0.32). LASSO regression identified that anthropometric and body composition parameters significantly predict Vata (R2 = 0.77, RMSE = 4.92) and Kapha (R2 = 0.60, RMSE = 6.77), while Pitta (R2 = 0.24, RMSE = 6.45) appeared independent of these measurements. This transdiagnostic relationship between Tridosha, body composition, and somatotype maps traditional Ayurvedic knowledge with contemporary science, and has potential implications for integrative healthcare applications. Anthropometry, Ayurveda, Ayusoft, Body Fat, Prakriti, Somatotype.

Obesity is a well-established risk factor for carpal tunnel syndrome (CTS), but body mass index (BMI) does not distinguish adiposity from skeletal muscle mass. The role of sarcopenia in CTS has received little attention. Sarcopenia may increase nerve vulnerability to compression. We examined whether appendicular lean mass index (ALMI) and ALMI-defined sarcopenia are associated with CTS independent of BMI. We retrospectively analyzed 193 consecutive patients aged 50 years or older who underwent carpal tunnel release by a single surgeon at a tertiary center over 4 years. Controls were 5665 age-matched participants from the 2022-2023 Korea National Health and Nutrition Examination Survey. ALMI-defined sarcopenia was compared between groups. Multivariable logistic regression was applied to examine the association between ALMI-defined sarcopenia and CTS, adjusting for BMI. Compared with controls, CTS patients exhibited a higher prevalence of sarcopenia in both men and women (p < 0.05). The association with sarcopenia was significant across most age and sex subgroups, whereas obesity was more evident in younger age groups (50-69 years). In multivariable models, sarcopenia showed a stronger association with CTS (OR 2.41, 95% CI 1.79-3.22) compared with BMI (OR 1.05, 95% CI 1.01-1.10). In this case-control study, both obesity and ALMI-based sarcopenia were associated with CTS, with sarcopenia showing a stronger association. These findings suggest an association between reduced muscle mass and CTS independent of BMI. Muscle mass assessment alongside BMI may help clinicians identify at-risk patients who might otherwise be overlooked by conventional obesity metrics.

Rethinking Muscle Health Assessment in GLP-1-Based Therapies for Obesity: Beyond Lean Mass.

Background Precise assessment of body composition is critical for managing obesity and sarcopenia, both of which are rising health concerns around the globe. While dual-energy X-ray absorptiometry (DXA) remains the gold standard, its high cost and limited accessibility hinder large-scale application. Multi-frequency bioelectrical impedance analysis (MF-BIA) shows promise as an alternative method, but validation in specific populations remains necessary. Objectives This study aimed to validate and evaluate the diagnostic accuracy of the InBody 970S MF-BIA device in estimating body composition parameters against DXA among healthy Malaysian adults. Methods A prospective validation study was conducted among 148 healthy adults aged 20–45 years. Participants underwent standardised assessments using MF-BIA (InBody 970S) and full-body DXA. Linear regression, paired t-tests, Bland–Altman plots, and diagnostic performance indices (sensitivity, specificity, PPV, NPV) were used to evaluate the agreement between methods for fat mass (BFM), lean body mass (LBM), fat-free mass (FFM), percent body fat (PBF), bone mineral content (BMC), and skeletal muscle mass index (SMI). Results MF-BIA showed strong correlations with DXA across all parameters (R 2 = 0.72–0.97). The predictive models for BFM, LBM, and PBF demonstrated high accuracy (e.g., BFM: R 2 = 0.96; LBM: R 2 = 0.96; FFM: R 2 = 0.97). Diagnostic agreement was particularly strong for sarcopenia (sensitivity = 95.1%, NPV = 98.0%) and obesity classification (specificity and PPV = 100%), though obesity sensitivity was lower (75.2%). Bland–Altman analysis confirmed acceptable limits of agreement. Conclusion MF-BIA offers a clinically valid, non-invasive, and accessible method for body composition assessment in Malaysian adults. Its utility in identifying obesity and sarcopenia risk supports its integration into routine clinical practice and public health screening, especially in resource-limited settings. Future work should explore ethnic-specific calibration to enhance its diagnostic precision across diverse populations.