system disorders, dementia, or cachexia. This group left the question open of whether sarcopenia as a term should be limited to use in older persons or used as a general term for adults of any age.
International Working Group on Sarcopenia (IWGS)
A group of American and European geriatricians and scientists from academia and industry, some of them involved in other definitions, met in Italy at the end of 2009, to arrive at a consensus definition of sarcopenia. Sarcopenia was defined as the age‐associated loss of skeletal muscle mass and function [14]. It should be considered in all older patients who present with observed declines in physical function, strength, or overall health, and especially in those who are bedridden, cannot independently rise from a chair, or who have a slow gait speed. A reduced muscle mass would confirm sarcopenia in this clinical setting.
Foundation for the National Institutes of Health
A few years later, an American initiative led by the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium used a different approach, mostly based on the pooled analysis of epidemiological studies, to define sarcopenia [16]. This initiative compiled data from nine studies in community‐dwelling older persons, with a pooled sample of 26 625 participants, to identify sex‐specific cut‐off points for low muscle mass (estimated by the appendicular lean mass adjusted for body mass index) and low muscle strength (measured as grip strength). These cut‐off points were shown to be associated with functional limitations (including slow gait speed, used as a component of other definitions).
Both the AWGS and the FNIH tried to overcome a major limitation of the EWGSOP definition – it did not recommend explicit cut‐off points for the parameters included in the definition – by proposing precise references to define normality for each variable. However, all definitions at this time agreed on the overall concept of sarcopenia as a compound of low muscle mass and reduced muscle function, defined by muscle strength, reduced physical performance, or both. The role of muscle quality, although mentioned in some initiatives, was still quite unclear.
Some important milestones derived from these definitions have been, among others, the recognition of sarcopenia as an independent condition with an ICD‐10‐CM code in 2016 [17], the development of the first clinical guideline for the condition [18], and the involvement of the European Medicines Agency in initiatives to develop a framework for drug development [19].
MATURITY OF SARCOPENIA: RECENT DEFINITIONS
A decade later, the EWGSOP met again, with a wider academic support (adding the endorsement of International Osteoporosis Foundation [IOF] and European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases [ESCEO] to ESPEN and EuGMS) to review and update the 2010 definition and reflect the advances in scientific, epidemiological, and clinical knowledge, and to facilitate the implementation of sarcopenia in mainstream clinical practice [20]. The updated consensus definition, named EWGSOP2, states that a person with low muscle strength and low muscle mass or quality will be diagnosed with sarcopenia. When sarcopenia impairs physical performance measures, it will be staged as severe sarcopenia. Sarcopenia is now understood as an organ (skeletal muscle) failure or insufficiency [21] that may appear acutely (in the setting of an acute disease or sudden immobility) or have a more chronic course. It aligns with the new function‐centered model proposed by the World Health Organization that focuses on intrinsic capacity (defined as a composite of all physical and mental capacities of an individual) [22].
The three main advances of the EWGSOP2 definition result from new insights: (i) sarcopenia is no longer considered primarily as a geriatric syndrome but as a muscle condition with an ICD‐CM diagnosis code (ICD‐10‐CM M62.84); (ii) loss of muscle quality is introduced as a new diagnostic criterion; and (iii) muscle strength is recognized as the best predictor of health outcomes. This definition intends to introduce sarcopenia in wide‐stream clinical practice as well, by offering a simple diagnostic algorithm. The AWGS has also published and updated definition [23]. Australia and New Zealand have opted to endorse the EWGSOP definitions [24]. Similar definitions focusing on the loss of strength or function in combination with a loss of lean mass have been published by the Society of Sarcopenia, Cachexia and Muscle wasting [25] and by the International Conference of Frailty and Sarcopenia Research [18]. Both also strongly recommended resistance exercise and the major treatment modality.
On the American side, the Sarcopenia Definition and Outcomes Consortium (SDOC) was funded by the National Institute on Aging (NIA) in 2015 with additional support of the FNIH. The SDOC aim is to develop evidence‐based diagnostic cut‐off points for lean mass and/or muscle strength that enable identification of people at risk or mobility disability as a target population of potential function‐promoting therapies [26]. As in the FNIH initiative, the SDOC is again using an epidemiological approach using several cohorts, mostly in the United States but also in Europe, in order to accumulate data from a large number of subjects and be able to calculate an algorithm predictive of sarcopenia outcomes. The project was completed in August 2019, and the final document with recommendations published in 2020 [27].
Sarcopenia is now extending well beyond older age, with recent initiatives trying to define sarcopenia within organ diseases [28] and even in pediatrics [29].
A global (European, Asian, American, and Australia/New Zealand) initiative is now in process to try to come to a consensus on an operational definition of sarcopenia that would finish this long trip.
NEW PLAYERS: BONE, FAT, AND MUSCLE
There are specific aspects not contemplated in current definitions of sarcopenia, as the role of fat, bone, or both which are still far to be settled [30]. They are discussed in detail in other chapters of this book. However, it seems pertinent to mention some aspects that are related to general definitions here.
Osteoporosis is a skeletal condition closely linked to sarcopenia, a condition that has been named osteosarcopenia. The coexistence of both conditions seems to increase the risk of falls and other outcomes associated with each condition alone [31]. There is still some discussion if osteosarcopenia should be defined by body composition (i.e. low muscle mass and low skeletal mass) or if muscle function should be part of the definition [32, 33].
Sarcopenia and obesity also coexist frequently in the so‐called sarcopenic obesity [34–37]. Increases in muscle fat and body weight have a strong influence in the accuracy and adjustment of most methods that estimate skeletal muscle mass. As in osteosarcopenia, a body composition approach (i.e. low muscle mass plus obesity defined as increased fat or by anthropometry) has coexisted in research with an approach that defines sarcopenia using functional measures, and efforts to refine the definition are under way.
THE FRONTIERS: FRAILTY, CACHEXIA, MALNUTRITION
Frailty, cachexia, and malnutrition are conditions that share some elements with sarcopenia: they are frequent in old age, predict adverse outcomes, and include in some way low muscle mass within their definitions, which may lead clinicians into problems when trying to sort out which condition predominates in a given patient [38, 39].
The Global Leadership Initiative on Malnutrition (GLIM) has proposed a definition of malnutrition that includes reduced muscle mass as one of the three phenotypic diagnostic criteria [40]. Thus, the finding of a low muscle mass with normal muscle function may suggest that malnutrition is present, although this may well be the start toward a malnutrition‐related sarcopenia.
Low muscle mass is also included in the most widely used definitions of cachexia, which also consider the role of low muscle strength [12, 41]. The border between disease‐related sarcopenia and cachexia (a time‐honored term used to describe severe weight loss and muscle wasting associated with severe inflammatory conditions) is quite blurred, usually depending on the degree of inflammation, the underlying pathophysiology, the triggering condition, and even