Appendicular muscle mass is most commonly assessed using dual X-ray absorptiometry (DXA) and bioimpedance analysis (BIA). However, the cutoff reference values for appendicular muscle mass are different between research groups. The AWGS divides appendicular muscle mass by height squared (DXA, 7.0 kg/m² for men and 5.4 kg/m² for women; BIA, 7.0 kg/m² for men and 5.7 kg/m² for women) [14], whereas the IWGS cutoff reference values are 7.23 kg/m² for men and 5.67 kg/m² for women [3]. In contrast, the FNIH sarcopenia project uses appendicular lean mass adjusted for BMI for cutoff values (<0.789 for men and <0.512 for women) [15], and the EWGSOP does not specify cutoff values.

Abdominal computed tomography (CT) is an accurate, practical approach to quantifying whole-body and regional skeletal muscle mass [16]. Cross-sectional imaging using CT is the preferred method for analyzing muscle mass in cancer patients, because CT is performed clinically for staging and diagnostic purposes [17, 18]. Core muscle size, measured as the total psoas cross-sectional area (TPA) at the third or fourth lumbar vertebra, is a precise indicator of total skeletal muscle mass [19]. The skeletal muscle index is calculated as the TPA divided by height squared and is associated with the severity of dysphagia in cancer patients [18]. Preoperative psoas muscle mass on the contralateral side is associated with postoperative gait speed following total hip arthroplasty for osteoarthritis [20]. The cutoff value when assessing the risk for the development of liver failure in Japanese cancer patients was defined as <5.67 cm²/m² in males and <3.95 cm²/m² in females [21].

Muscle strength is mainly assessed by grip strength; it is the default evaluation given the low cost, availability, and ease of use of this equipment during evaluations. The cutoff values for grip strength are as follows: EWGSOP, <30 kg for men and <20 kg for women [1]; AWGS, <26 kg for men and <18 kg for women [14]; and FNIH sarcopenia project, <26 kg for men and <16 kg for women [15]. The IWGS diagnostic criteria for sarcopenia do not include muscle strength assessment [3].

Knee extension is another method used to assess muscle strength; assessed in relation to body weight, it correlates with physical function [22]. A threshold ratio of knee extension strength/body weight between 2.78 kPa/kg and 2.86 kPa/kg is considered a potential cutoff value by which to identify women presenting with greater functional impairments [22]. Knee extension strength was determined to be a better predictor of functional performance than was handgrip strength, but only among residents in assisted living facilities [23].

Physical performance is primarily assessed by usual gait speed. The EWGSOP and the AWGS cutoff values for usual gait speed are <0.8 m/s [1, 14], whereas the IWGS cutoff value is <1 m/s [3]. In the FNIH sarcopenia project, physical performance assessment is not included in the diagnostic criteria for sarcopenia [15]. The Short Physical Performance Battery that includes gait speed, ability and time to rise from a chair five times, static balance tests, the timed up and go test that measures the time to rise from a chair and walk a short distance, and the 6-min walk test is another method to assess physical performance [24].

The etiology of age-related sarcopenia can be multifactorial in that it can include decreased activity (bed rest), low protein intake, chronic inflammation, increased oxidative stress, lipotoxicity, reduced neuronal stimulation, hormonal changes, increased myostatin concentrations, and/or decreased blood capillary flow [25]. The ubiquitin-proteasome system (atrogin-1 and MuRF-1), which is important in protein degradation in acute muscle atrophy, seems not to be implicated in age-related sarcopenia [26]. In contrast, the dysfunction of autophagy-dependent signaling seems to be profoundly involved in age-related sarcopenia [27]. Sarcopenic conditions appear to be characterized by a marked defect of autophagy signaling, because p62/SQSTM1, but not LC3, accumulates in the sarcopenic muscle of mice [28]. It remains to be elucidated whether the myostatin-Smad pathway is fundamental to the development of sarcopenia [27].

Activity-related sarcopenia can result from prolonged bed rest, a sedentary lifestyle, and/or deconditioning or zero-gravity conditions [1]. For this type of sarcopenia, the loss of skeletal muscle mass and strength occurs at an approximate rate of 0.5% (range, 0.3–4.2%) total muscle mass per day [29]. Prolonged disuse (>10 days) can result in a decline in basal and postprandial rates of muscle protein synthesis, without an apparent change in muscle protein breakdown [29].

Hospital-associated deconditioning is characterized by a functional decline that occurs during acute hospitalization due to illness or injury and is unrelated to a specific neurological or orthopedic insult [6]. Hospital-associated deconditioning includes activity-related sarcopenia. In our previous cohort study [30, 31], 88–91% of patients with hospital-associated deconditioning were malnourished, and the decline in nutritional status resulted in a decline in the rehabilitation outcome.

Nutrition-related sarcopenia results from inadequate dietary intake of energy and/or protein and can be associated with either malabsorption or gastrointestinal disorders [1]. Adult malnutrition is classified as malnutrition in the context of acute illness or injury or invasion, chronic illness or cachexia, and/or social or environmental circumstances that can lead to starvation [32]. Nutrition-related sarcopenia includes starvation, and disease-related sarcopenia includes invasive injury and cachexia.

Older patients with hospital-associated deconditioning can be at risk for an inadequate energy intake that does not meet their basal energy expenditure. A total of 75 (44%) out of 169 patients fell into this category based on one report [31]. The energy intake of older patients with hospital-associated deconditioning seems to often be suboptimal, resulting in nutrition-related sarcopenia. Nutrition-related sarcopenia causes hepatic glycogen depletion. Glycogen is stored only in the liver and muscles in humans. Muscle glycogen is stored as a readily available fuel source for muscle tissue; it is not released into the blood as a source of glucose following glycogenolysis. Therefore, glucose is synthesized from glycogenic amino acids derived via skeletal muscle catabolism in nutrition-related sarcopenia. A chronic negative energy and/or a protein imbalance result in nutrition-related sarcopenia.

Disease-related sarcopenia is usually associated with advanced organ failure (heart, lung, liver, kidney, and brain), inflammatory disease, malignancy, and/or endocrine disease [1]. It is characterized by invasion, cachexia, and neuromuscular disorders. An intensive care unit-acquired weakness [33] can be classified as disease-related sarcopenia. Acute inflammatory crises triggered by events such as sepsis, pulmonary decompensation, emergency surgery, and/or trauma can result in profound muscle wasting via mechanisms of action that may include tumor necrosis factor-α-mediated catabolism, mitochondrial dysfunction, and/or a reduction of muscle protein synthesis [34].

Phases of acute inflammation or invasion can be classified as catabolic and anabolic. In a catabolic phase, both muscle and adipose tissue are degraded by proinflammatory cytokines. In an anabolic phase, both muscle and adipose tissue can be synthesized and increased by an appropriate nutritional management and exercise. Clinically, a catabolic phase features a muscle that is more degraded than adipose tissue. In patients with a critical illness, the loss of muscle mass can reach 1 kg/day due to conditions causing severe inflammatory responses [35]. Disease-related sarcopenia can be further complicated by the other causes of secondary sarcopenia outlined previously that can compound the sarcopenic effect in the face of hospital-associated deconditioning.

Older patients with a hip fracture and hospital-associated deconditioning can complicate all causes of sarcopenia [6, 36]. Activities of daily living are independent in frail older people with only age-related sarcopenia. However, the functional reserve in frail individuals is considered limited. For example, if they develop a hip fracture, their skeletal muscle mass can rapidly deteriorate as the other secondary causes of sarcopenia come into play.

Most patients with a hip fracture undergo surgery, and during the perioperative period, they tend to be prescribed bed rest and fasting. In acute hip fracture inpatients, the total 24-h energy and protein intakes before a multidisciplinary nutritional care intervention were 707 kcal and 33.8 g, respectively [37]. Collectively, extended bed rest, poor nutritional support, and the invasive nature of a surgery with its inflammatory sequelae can contribute to the type of skeletal muscle catabolism indicative of secondary sarcopenia (Fig. 7.2).

Resistance training has been shown to be the most effective intervention when striving to combat age-related sarcopenia, because it induces skeletal muscle hypertrophy which can enhance muscle strength [4], even in older people over 75 years [38]. In the Cochrane Database of Systematic Reviews, progressive resistance strength training was also reported as an effective intervention for improving physical functioning in older people by increasing muscle strength and gait speed[39].

Protein and amino acid supplementation can contribute to counteracting sarcopenia, because low protein intake is known to be associated with declining muscle mass in older adults [40]. In a systematic review, nutritional supplementation was reported to improve both muscle mass and muscle strength in older people with sarcopenia [41]. A meta-analysis showed that protein supplementation can also increase muscle mass and strength gains during prolonged resistance-type exercise training in sarcopenia [42]. However, another meta-analysis reported that amino acid/protein supplements did not increase lean body mass and muscle strength significantly in older people [43]. Furthermore, in a recent meta-analysis, combining protein supplementation with resistance training did not seem to increase muscle mass or strength [44]. Considering these results, whole-protein supplementation failed to show a consistent effect on muscle mass, strength, or function [45].

Increasing physical activity and avoiding prolonged and unnecessary bed rest or a sedentary lifestyle are good general strategies for mitigating activity-related sarcopenia, and if needed, rehabilitation may be advised. Early rehabilitation may be safe and feasible for critically ill patients in the intensive care unit when medically prescribed [46, 47]. Therapies to combat the loss of muscle mass have focused largely on strategies using resistance exercises and/or nutrition, but with mixed success [48]. Iatrogenic sarcopenia due to unnecessary fasting and bed rest in hospitalized older people should be avoided.

In a recent randomized controlled trial, an early nutritional intervention using nutritional supplements (600 kcal, 20 g/d protein added to a standard diet) together with early rehabilitation preserved the muscle mass and independence of ill, older patients hospitalized for acute diseases [49]. A combination of early rehabilitation and nutritional intervention seemed to be a highly effective method to treat and ameliorate activity-related sarcopenia, because many patients with hospital-associated deconditioning can be malnourished [30, 31].

Recommendations for the treatment of nutrition-related sarcopenia focus on the maintenance of a positive energy and protein balance. Daily energy requirements in cases of nutrition-related sarcopenia can be calculated as daily energy expenditure plus daily energy accumulation (200–750 kcal/day). The excess energy required to gain 1 kg of body weight was between 8856 and 22,620 kcal/kg in malnourished nursing home patients [50]. Gaining weight is more difficult in older compared with younger people. Therefore, aggressive nutrition care management is often necessary to improve nutritional status.

Prevention of nutrition-related sarcopenia is important, especially in some older inpatients with hospital-associated deconditioning who are prescribed peripheral parenteral nutrition that furnishes less than 300 kcal/day in the absence of an oral caloric intake and enteral nutrition [51]. Identification of iatrogenic sarcopenia in older hospitalized patients due to nutritional management issues should be addressed as soon as possible to determine if additional nutritional support can be provided.

Resistance training to improve muscle mass should be avoided if energy and protein balance is negative, because this type of exercise, as well as endurance training, exacerbates the negative energy balance and can worsen nutrition-related sarcopenia. Resistance training to improve muscle mass should be performed only if energy and protein are balanced or positive. However, prolonged bed rest should be avoided if energy and protein balance is negative, because inactivity enhances catabolic responses to calorie restriction [52]. Light activity and exercise should be performed to prevent activity-related sarcopenia.

The most important factor in disease-related sarcopenia is treatment of the disease. Appropriate treatment of disease-related sarcopenia is different in the catabolic phase compared to the anabolic phase. In a catabolic state, muscle degradation and endogenous energy production are usually increased, and disease-related sarcopenia can develop rapidly. Nutrition care management under these circumstances should be modest (15–30 kcal/kg/day), and daily energy expenditure beyond energy intake should be curtailed because of increasing endogenous energy production. Light load activity and exercise should be performed to prevent activity-related sarcopenia. Anabolic phase is the state during which muscle mass and adipose tissue can be gained as a result of physical exercise and activity and appropriate nutrition care management. Nutrition care management in the anabolic phase should be tailored to the patient’s daily energy expenditure plus daily energy accumulation (200–750 kcal/day) to improve muscle mass and strength. Resistance training to improve muscle mass is encouraged in anabolic phase.

In critically ill patients, neuromuscular electrical stimulation added to standard treatment has been proved to be more effective than the standard treatment alone in the prevention of skeletal muscle weakness [53]. In the Cochrane Database of Systematic Reviews, it has been shown that no harm has been associated with the following related to muscle disease: moderate-intensity strength training in myotonic dystrophy and facioscapulohumeral muscular dystrophy and aerobic exercise training in dermatomyositis, polymyositis, and myotonic dystrophy type I [54]. However, there is insufficient evidence to conclude that they offer any benefit. In mitochondrial myopathy, aerobic exercise combined with strength training appeared to be safe and may be effective at increasing submaximal endurance capacity [54].

Smoking cessation can be recommended for the prevention and treatment of sarcopenia. Cigarette smoking may contribute to the development of sarcopenia according to a meta-analysis [55].