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As reference methods are not available for identifying low skeletal muscle mass in clinical practice, the European Group on Sarcopenia in Older People the Asian Working Group for Sarcopenia and the International Consensus for Cancer Cachexia guidelines accept bioelectrical impedance analysis (BIA) as an option for sarcopenia and cachexia assessment. Using different BIA equations, several components that represent ‘muscularity’ can be assessed. Total skeletal muscle mass or appendicular skeletal muscle mass normalized in relation to height (skeletal muscle mass index or appendicular skeletal muscle index, respectively) is the most common term used in the consensus. These terms are similar, but they should not be used as synonymous. Both terms can be used to define sarcopenia, but adequate equations and cut‐off values should be used according to the studied population. However, there is a disagreement between the sarcopenia definition assessed by using BIA from the European Group on Sarcopenia in Older People and Cachexia Consensus, and this can lead to an overestimation of sarcopenia and, consequently, cachexia. An effort should be made to standardize the terminology employed by the Societies to define low muscularity and sarcopenia by using BIA. Future validation studies may show the need for specific cut‐off values for each population using this method.

This paper gives a brief overview of common non-invasive techniques for body composition analysis and a more in-depth review of a body composition assessment method based on fat-referenced quantitative MRI. Earlier published studies of this method are summarized, and a previously unpublished validation study, based on 4753 subjects from the UK Biobank imaging cohort, comparing the quantitative MRI method with dual-energy X-ray absorptiometry (DXA) is presented. For whole-body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and quantitative MRIs show excellent agreement with linear correlation of 0.99 and 0.97, and coefficient of variation (CV) of 4.5 and 4.6 per cent for fat (computed from AT) and LT, respectively, but the agreement was found significantly lower for visceral adipose tissue, with a CV of >20 per cent. The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat, in combination with rapid scanning protocols and efficient image analysis tools, makes quantitative MRI a powerful tool for advanced body composition assessment.

In 2008 the National Center for Health Statistics released a dual energy x-ray absorptiometry (DXA) whole body dataset from the NHANES population-based sample acquired with modern fan beam scanners in 15 counties across the United States from 1999 through 2004. The NHANES dataset was partitioned by gender and ethnicity and DXA whole body measures of %fat, fat mass/height(2), lean mass/height(2), appendicular lean mass/height(2), %fat trunk/%fat legs ratio, trunk/limb fat mass ratio of fat, bone mineral content (BMC) and bone mineral density (BMD) were analyzed to provide reference values for subjects 8 to 85 years old. DXA reference values for adults were normalized to age; reference values for children included total and sub-total whole body results and were normalized to age, height, or lean mass. We developed an obesity classification scheme by using estabbody mass index (BMI) classification thresholds and prevalences in young adults to generate matching classification thresholds for Fat Mass Index (FMI; fat mass/height(2)). These reference values should be helpful in the evaluation of a variety of adult and childhood abnormalities involving fat, lean, and bone, for establishing entry criteria into clinical trials, and for other medical, research, and epidemiological uses.

The first reports of accurate skeletal muscle mass measurement in human subjects appeared at about the same time as introduction of the sarcopenia concept in the late 1980s. Since then these methods, computed tomography and MRI, have been used to gain insights into older (i.e. anthropometry and urinary markers) and more recently developed and refined methods (ultrasound, bioimpedance analysis and dual-energy X-ray absorptiometry) of quantifying regional and total body skeletal muscle mass. The objective of this review is to describe the evolution of these methods and their continued development in the context of sarcopenia evaluation and treatment. Advances in these technologies are described with a focus on additional quantifiable measures that relate to muscle composition and ‘quality’. The integration of these collective evaluations with strength and physical performance indices is highlighted with linkages to evaluation of sarcopenia and the spectrum of related disorders such as sarcopenic obesity, cachexia and frailty. Our findings show that currently available methods and those in development are capable of non-invasively extending measures from solely ‘mass’ to quality evaluations that promise to close the gaps now recognised between skeletal muscle mass and muscle function, morbidity and mortality. As the largest tissue compartment in most adults, skeletal muscle mass and aspects of muscle composition can now be evaluated by a wide array of technologies that provide important new research and clinical opportunities aligned with the growing interest in the spectrum of conditions associated with sarcopenia.

Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases) and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of a universally established SO definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and Methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into stage I in the absence of clinical complications or stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing data sets, to study the predictive value, treatment efficacy and clinical impact of this SO definition.

The term sarcopenia was introduced in 1988. The original definition was a “muscle loss” of the appendicular muscle mass in the older people as measured by dual energy x‐ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC‐F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease‐related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age‐related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age‐related and disease‐related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

In December 2024, the Society on Cachexia and Wasting Disorders (SCWD) hosted a Regulatory and Trial Update Workshop in Washington, D.C., bringing together experts from academia, industry, and the US Food and Drug Administration (FDA). This article summarizes key topics discussed during the meeting, including diagnostic challenges, emerging assessment methods, and trial endpoints. The D3‐creatine dilution technique was highlighted as a promising tool for evaluating muscle mass. Additionally, the workshop addressed variability in computed tomography‐based lumbar skeletal muscle index measurements, emphasizing sources of variation at the instrument, imaging, and reader levels, as well as biological and clinical fluctuations. Discussions also focused on clinical trial endpoints for sarcopenia, particularly validated physical performance measures such as the Short Physical Performance Battery (SPPB), habitual gait speed, stair‐climb tests, and the 6‐min walk test. Furthermore, novel therapeutic approaches were explored, including 20‐hydroxyecdysone, enobosarm, anamorelin, ponsegromab, and nutritional supplementation, alongside broader strategies targeting myostatin‐activin signalling inhibition and Akt pathway activation. During the meeting, it was made clear that from a regulatory treatment development standpoint, clinically meaningful changes in patient‐reported outcomes, physical function and/or morbidity/mortality need to be shown. If the latter is not an efficacy endpoint, safety needs to be documented. Given that the population that may be addressed in aging associated sarcopenia is vast, the safety requirement standards applied for studies may be equivalent to those of studies in type 2 diabetes mellitus. Some argued at the meeting that this would make study programs so large that from an economic standpoint only therapies that significantly impact on morbidity/mortality outcomes have a chance to be considered commercially feasible for development.

Sarcopenia, sarcopenic obesity, frailty, and cachexia have in common skeletal muscle (SM) as a main component of their pathophysiology. The reference method for SM mass measurement is whole-body magnetic resonance imaging (MRI), although dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) serves as an affordable and practical SM surrogate. Empirical equations, developed on relatively small and diverse samples, are now used to predict total body SM from ALM and other covariates; prediction models for extremity SM mass are lacking. The aim of the current study was to develop and validate total body, arm, and leg SM mass prediction equations based on a large sample (N = 475) of adults evaluated with whole-body MRI and DXA for SM and ALM, respectively. Initial models were fit using ordinary least squares stepwise selection procedures; covariates beyond extremity lean mass made only small contributions to the final models that were developed using Deming regression. All three developed final models (total, arm, and leg) had high R 2 s (0.88–0.93; all p < 0.001) and small root-mean square errors (1.74, 0.41, and 0.95 kg) with no bias in the validation sample (N = 95). The new total body SM prediction model (SM = 1.12 × ALM – 0.63) showed good performance, with some bias, against previously reported DXA-ALM prediction models. These new total body and extremity SM prediction models, developed and validated in a large sample, afford an important and practical opportunity to evaluate SM mass in research and clinical settings.

Knowledge of human body composition at the dawn of the twentieth century was based largely on cadaver studies and chemical analyses of isolated organs and tissues. Matters soon changed by the nineteen twenties when the Czech anthropologist Jindřich Matiegka introduced an influential new anthropometric method of fractionating body mass into subcutaneous adipose tissue and other major body components. Today, one century later, investigators can not only quantify every major body component in vivo at the atomic, molecular, cellular, tissue-organ, and whole-body organizational levels, but go far beyond to organ and tissue-specific composition and metabolite estimates. These advances are leading to an improved understanding of adiposity structure-function relations, discovery of new obesity phenotypes, and a mechanistic basis of some weight-related pathophysiological processes and adverse clinical outcomes. What factors over the past one hundred years combined to generate these profound new body composition measurement capabilities in living humans? This perspective tracks the origins of these scientific innovations with the aim of providing insights on current methodology gaps and future research needs.

Computed tomography (CT) is a valuable assessment method for muscle pathologies such as sarcopenia, cachexia, and myosteatosis. However, several key underappreciated scan imaging parameters need consideration for both research and clinical use, specifically CT kilovoltage and the use of contrast material. We conducted a scoping review to assess these effects on CT muscle measures. We reviewed articles from PubMed, Scopus, and Web of Science from 1970 to 2020 on the effect of intravenous contrast material and variation in CT kilovoltage on muscle mass and density. We identified 971 articles on contrast and 277 articles on kilovoltage. The number of articles that met inclusion criteria for contrast and kilovoltage was 11 and 7, respectively. Ten studies evaluated the effect of contrast on muscle density of which nine found that contrast significantly increases CT muscle density (arterial phase 6–23% increase, venous phase 19–57% increase, and delayed phase 23–43% increase). Seven out of 10 studies evaluating the effect of contrast on muscle area found significant increases in area due to contrast (≤2.58%). Six studies evaluating kilovoltage on muscle density found that lower kilovoltage resulted in a higher muscle density (14–40% increase). One study reported a significant decrease in muscle area when reducing kilovoltage (2.9%). The use of contrast and kilovoltage variations can have dramatic effects on skeletal muscle analysis and should be considered and reported in CT muscle analysis research. These significant factors in CT skeletal muscle analysis can alter clinical and research outcomes and are therefore a barrier to clinical application unless better appreciated.