Continuing Education Activity

Sarcopenia is a musculoskeletal disease in which muscle mass, strength, and performance are significantly compromised with age. Sarcopenia most commonly affects elderly and sedentary populations and patients who have comorbidities that affect the musculoskeletal system or impair physical activity. This activity reviews the evaluation and treatment of sarcopenia and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Summarize the etiology of sarcopenia.
• Describe the pathophysiology of sarcopenia.
• Outline the screening indications for sarcopenia.
• Explain the importance of collaboration and communication amongst the interprofessional team to improve outcomes for patients affected by sarcopenia.

Introduction

Sarcopenia is a musculoskeletal disease generally defined by the progressive loss of muscle mass and strength, particularly in elderly populations.[1] The diagnosis of sarcopenia encompasses decreased levels of the following 3 traits: muscle strength, muscle quantity or quality, and physical performance.[1] Such musculoskeletal degeneration may impede daily activities and demonstrates predictive value regarding unfavorable postoperative outcomes, and increased complication rates, mortality, and morbidity in major surgical procedures.[2][3][4][5][6][7] 

Additionally, sarcopenia is strongly associated with a greater incidence of falls and increased fracture risk.[8] Furthermore, decreased muscle mass or muscle function, both criteria for sarcopenia, are risk factors for loss of independence in patients over the age of 90 years old.[9] Sarcopenia has become an increasingly studied condition and recently received a specific International Classification of Disease (ICD) 10 code to better distinguish it from similar or co-existing diseases that manifest with muscular wasting.

Etiology

Causes of sarcopenia are generally attributable to the natural processes of aging, which are not entirely understood and are multifaceted.[10] Factors contributing to its development include decreased type II muscle fiber size and number, inactivity, obesity, insulin resistance, reduced androgen and growth factor serum concentrations, inadequate protein intake, and a blunted muscle protein synthesis (MPS) response to protein meals or resistance exercise.[11][12][13][14][15][16][17]

Additionally, sarcopenia is associated with and may, in part, be caused by several chronic diseases that negatively affect the musculoskeletal system and physical activity.[10] These include chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus (DM), human immunodeficiency virus (HIV), and cancer.[18][19][20][21][22][23] 

Theoretically, the role of these disease processes on sarcopenia may exert themselves primarily through direct effects on muscle function, or secondarily through retardation of physical activity or caloric restriction.[24] It should be noted that in the context of cancer, cachexia is more commonly assessed as an indicator of tissue loss than is sarcopenia, though the clinical presentations of both diseases demonstrate significant overlap.[25]

Epidemiology

The prevalence of sarcopenia is estimated within the ranges of 5 – 13% and 11 – 50% in patients aged 60 and above, and 80 and above, respectively.[26] The worldwide prevalence of sarcopenia in patients over the age of 60 is estimated to be 10%.[27] Variations observed among studies are likely due to inconsistent diagnostic criteria, and heterogeneous populations studied. Sarcopenia almost exclusively affects elderly populations and affects both sexes equally.[27] Data regarding sarcopenia and ethnicity is inconsistent among studies. Furthermore, the prevalence of sarcopenia is greater in patients with chronic diseases such as COPD, CHF, CKD, DM, HIV, and cancer.[18][19][20][21][22][23]

Pathophysiology

Generally, a significant decline of type II, but not type I muscle fibers are observed in sarcopenic patients.[28] Several mechanisms of the underlying pathophysiology of sarcopenia have been described:

• Age-related declines in anabolic hormone serum concentrations: Normal physiological serum levels of anabolic hormones such as testosterone, human growth hormone (HGH), and insulin-like growth factor-1 (IGF-1) have been demonstrated to function in the development, maintenance, or rejuvenation of muscle tissue.[29][30][31][32] Age-related declines of such hormones are observed in patients with sarcopenia and thus, support this underlying pathophysiology of the disease.[33]
• Insulin resistance with “sarcopenic obesity”: Aging patients often experience changes in body composition represented by increased adipose tissue alongside decreased muscle mass, coined as “sarcopenic obesity.”[34] These changes are associated with metabolic dysfunction, including insulin resistance (IR), leading to the accumulation of visceral fat mass.[35] Additionally, IR is inversely associated with skeletal muscle mass.[36] Such pathophysiology is likely mediated via dysfunction of insulin’s exerted effects on skeletal muscle – insulin resistance impairs the anti-proteolytic and MPS enhancing properties of the hormone on skeletal muscle tissue.[37] Similarly, diminished lean body mass reduces uptake of glucose into skeletal muscle, further propagating IR.[38][39]
• Age-related neurodegeneration: Progressive neurodegeneration is a commonly observed phenomenon in aging populations.[40] Aging is accompanied by a decline of alpha motor neurons in the spinal cord, loss of peripheral nerve fibers, and reduced number of neuromuscular junctions.[33][41] Considering the role of the neurological system in muscle fiber recruitment, current evidence supports neurodegeneration as underlying pathophysiology for reduced muscle strength and size in sarcopenia.[41]
• Age-related increase in inflammatory markers: Elevated levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF), interleukin (IL)-6, and IL-1 are observed in elderly populations.[42] The catabolic effects that may be exerted by these cytokines on skeletal muscle are well documented and may present a mechanism in which sarcopenia develops with age.[43][44][45]

History and Physical

Sarcopenia is characterized by decreased muscle strength, quantity, and physical performance. Patients with sarcopenia are often elderly, sedentary, and may present with various comorbidities or disabilities, with a subsequent decrease in function and quality of life. A patient history consistent with sarcopenia includes progressive loss of muscle mass, strength, and function to the extent that daily activities become increasingly difficult to accomplish.

Evaluation

Patient evaluation for sarcopenia includes several modalities and screening tools, some of which are more readily available and practical than others. Evaluation ranges from screening questionnaires to radiographic imaging to the assessment of muscle mass cross-sectional area (CSA).[1][26] Additionally, the European working group on sarcopenia in older people 2 (EWGSOP2) describes an algorithm that presents as follows: "find-assess-confirm-severity" or F-A-C-S.[1] 

Screening Tools to Identify Probable Sarcopenia

• Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire: The SARC-F questionnaire is a screening tool that can be rapidly implemented by clinicians to identify probable sarcopenic patients. The questionnaire screens patients for self-reported signs suggestive of sarcopenia, which include deficiencies in strength, walking, rising from a chair, climbing stairs, and experiencing falls.[46] Each of the self-reported parameters receives a minimum and maximum score of 0 and 2, respectively, with the greatest maximum SARC-F score being 10.[47] Data suggests that a SARC-F score of ≥4 best predicts the need for further, more comprehensive evaluation.[1][46]

Assessing sarcopenia: muscle strength

• Handgrip test: Generally, handgrip strength is one of the two methods utilized to quantify muscle strength in patients with suspected sarcopenia. Handgrip strength correlates with strength in other muscles and is therefore used as a surrogate to detect deficits in overall strength.[48] Additionally, decreased handgrip strength predicts poor patient outcomes, including increased lengths of stay (LOS), functional deficits, and death.[48][49] Accurate grip strength measurement and interpretation of results rely on a calibrated dynamometer and relevant reference populations.[50] The Jamar dynamometer is a validated tool in measuring grip strength and may be used for this assessment.[51] The suggested cutoff point for handgrip is <27 kg and <16 kg, for males and females, respectively.[52]
• Chair stand test: The chair stand test may be used as a proxy to gauge lower extremity strength, particularly the quadriceps muscles. The chair stand test measures the number of times a patient can stand and sit from a chair, without the use of their arms, over 30 seconds.[53] This test has been established as a valid indicator of lower extremity strength in community-dwelling populations.[54] The suggested cutoff point for the chair stand test is >15 seconds for five rises.[53] 

Confirming sarcopenia: Muscle quantity or quality

To date, there is no consensus on the most effective modality for confirming sarcopenia. Each comes with their strengths and weaknesses, and often, greater accuracy presents with the cost of inconvenience. Ultimately the goal of these modalities is to determine whether patients meet the requirement of sarcopenia through quantifying total body skeletal muscle mass (SMM), appendicular skeletal muscle mass (ASM), or the cross-sectional area of a specific muscle. Because overall body mass is correlated with SMM, SMM, or ASM, it may be adjusted for height or BMI, yielding ratios in the format of (ASM/height^2), (ASM/weight), or (ASM/BMI). The recommended cutoff for ASM is <20 kg and <15 kg, for males and females, respectively.[55] Similarly, the recommended cutoff for ASM/height^2 is <7.0 kg/m^2 and <5.5 kg/m^2 for males and females, respectively.[56]

• Magnetic resonance imaging (MRI): Considered a "gold standard" modality for confirming sarcopenia, MRI can provide highly accurate measurements of total body muscle mass.[57][58][59] However, this modality requires highly trained providers, lacks portability, presents little cost-effectiveness, and is therefore rarely used in the primary care setting.[60][58]
• Computed tomography (CT): Also considered a "gold standard" for accurate lean muscle mass measurement, CT is rarely used in the primary care setting for similar reasons than MRI.[58] However, settings in which CT is routinely performed, such as trauma or surgery, this modality presents greater value and practicability, as demonstrated in previous literature.[61] More specifically, CT measured psoas cross-sectional area (PCSA) at the level of the 3rd lumbar vertebrae has consistently predicted outcomes among patient populations in the contexts of gastrointestinal cancer, heart valve surgery, orthopedic trauma, thoracolumbar surgery[62][63][64][65]
• Dual-energy X-ray absorptiometry (DEXA): While not as accurate as either CT or MRI, DEXA presents with greater convenience, and is, therefore, a more widely available and practical modality for confirmation of sarcopenia.[1][66]
• Bioelectrical impedance analysis (BIA): Perhaps the most widely available and portable modality of muscle mass quantification, BIA may also be used to confirm sarcopenia.[1]  

Measuring physical performance to identify sarcopenia severity:

Once sarcopenia is confirmed through body composition assessment, the severity of the condition is determined by measuring physical performance. Suggested tests and their respective cutoff points for sarcopenia severity as recommended by the EWGSOP2 are listed below. 

• Gait speed test: Gait speed tests are simple to use in practice and predict adverse effects associated with sarcopenia.[67] The "4-meter usual walking speed test" is practical and can be used to assess sarcopenia severity.[68][69] The test measures time taken for a patient to travel 4 meters at their usual walking pace. A speed of ≤0.8 m/s may be indicative of severe sarcopenia.[70]
• Short physical performance battery (SPPB): The SPPB test is composed of 3 timed tasks: chair stand tests, standing balance, and walking speed. The minimal and maximal achievable scores are 0 (low performance) and 12 (high performance), respectively. A score of ≤8 is an indicator of poor physical performance and may be indicative of greater sarcopenia severity.[1][71]
• Timed-up and go test (TUG): The TUG test observes the time taken for a patient to rise from a chair, walk 3 meters away from, and 3 meters back to the chair, terminating the test in a sitting position. Time ≥20 seconds is indicative of physical deficits, though the study used to support this recommendation failed to assess male populations and therefore, may only apply to elderly female populations.[72]
• The 400-meter walk test: In the 400-meter walk test, a patient attempts to walk in a series of 20, 20-meter laps as quickly as possible, with a maximum of 2 minutes rest between each lap. The inability to complete or requiring ≥6 min to complete the entire 400-meters is concerning and may suggest greater sarcopenia severity.[1][73]

Treatment / Management

Physical activity, particularly resistance training, effectively attenuates muscle loss and improves strength in sarcopenia, providing a means of both preventing and managing the condition.[74][75] Additionally, increasing total protein intake through supplementation or food sources can help prevent and manage sarcopenia. Specifically, consuming 20-35 grams of protein per meal is advised, as such amounts provide sufficient amino acid content to maximize MPS, thus minimizing age-related muscle loss.[76] Additionally, patients with sarcopenia are recommended to consume 1.0 - 1.2 g/kg (body weight)/day.[77] Furthermore, the greatest effects are observed when resistance training and high protein diets are combined and appear to act synergistically.[78]

Differential Diagnosis

Considering the high probability that sarcopenia may co-exist with the below conditions and considering the overlap between conditions, an accurate differential diagnosis may be difficult. 

• Frailty: While sarcopenia and frailty present with significant overlap of symptoms, they remain distinguishable. Frailty is defined as multi-system impairment and encompasses a broader range of dysfunction than sarcopenia, whereas sarcopenia mainly includes the musculoskeletal system. One condition may contribute directly to the other, as they often co-exist in elderly patients.[79][80]
• Malnutrition: Both malnutrition and sarcopenia present with low muscle mass, though sarcopenia more often presents with the additional loss of function. Additionally, as a function of caloric restriction, reduced fat mass is observed in patients with malnutrition – this is often not the case with sarcopenia. Functional tests for strength and performance may be administered to rule out malnutrition.[1]
• Cachexia: Cachexia is thought to have a more complex etiology than sarcopenia. Cachexia is described as severe weight loss and muscle-wasting associated with conditions such as HIV, cancer, and end-stage organ failure. While cachexia and sarcopenia may co-exist, a patient with severe muscle wasting diseases such as HIV or cancer is more likely to have cachexia. [81] Additionally, the Glasgow prognostic score can be utilized to distinguish the two conditions.[82]
• Osteoarthritis of the hand: Patients with osteoarthritis of the hand may elicit a false positive test when performing the handgrip strength test. In cases where severe osteoarthritis is suspected, patients may perform methods to measure isometric torque of the lower limb to more accurately assess or rule out sarcopenia.[1][83]

Prognosis

The prognosis of sarcopenia largely depends on age, comorbidities, falls, and fractures. Additionally, patients who have sarcopenia undergoing surgical procedures have less favorable outcomes than those without sarcopenia. These include an increased risk of postoperative complications, falls, LOS, fractures, and greater morbidity and mortality. Ultimately, the prognosis of sarcopenia alone is uncertain and not well studied, though consistent evidence demonstrates sarcopenia as an indicator of poor prognosis in several medical conditions and surgical procedures.[84]

Complications

Fall, fracture, and nosocomial infection risk in the elderly: In a meta-analysis of 33 studies encompassing 45,926 patients, Yeung et al. found that sarcopenia significantly increases both fall and fracture risk in the elderly.[8] Additionally, sarcopenia increases the risk of nosocomial infection in elderly populations.[85]

Sarcopenia complications in medicine: Sarcopenia is associated with increased mortality in patients with end-stage renal disease, pancreatic cancer, and chronic heart failure.[86][87] Additionally, sarcopenia is associated with increased dose-limiting toxicities (DLT) in patients undergoing chemotherapy for renal cell carcinoma, hepatocellular carcinoma, and breast cancer.[88][89][90]

Sarcopenia complications in surgery: Sarcopenia is associated with increased postoperative complication risk in patients undergoing general surgical procedures and liver transplant surgery.[91][92] Additionally, sarcopenia is associated with greater mortality in patients undergoing general surgical procedures and colorectal surgery.[91][93]

Deterrence and Patient Education

Patients should maintain proper health etiquette and receive routine physicals, making clinicians aware of any perceived changes in health, weight, body composition, or function. Additionally, patients should be made aware of the potential dangers of sarcopenia and how it may affect them and their loved ones, especially in those with multiple comorbidities.

Prevention appears to be the most effective way to deal with the potential issues that sarcopenia presents in the elderly. Nonetheless, prevention, management, and treatment of sarcopenia are most effectively achieved by maintaining physical activity and increased protein intake. Specifically, patients should be educated on the daily and per meal basis protein recommendations. Furthermore, patients should be educated on the benefits of resistance training, in combination with the aforementioned recommendations, to avoid developing or treat or manage sarcopenia.

Enhancing Healthcare Team Outcomes

Sarcopenia presents a great financial burden on the field of healthcare, as well as decreased quality of life in those who suffer from it. Clinicians who care for elderly patients must detect and treat sarcopenia early to reduce these burdens and improve the outcomes of the condition.[1] [Level 4]

To achieve optimal outcomes in clinical practice, advancing interprofessional communication, pharmacological research, patient education, and patient adherence to recommendations is imperative. Currently, the most effective modalities available to fight sarcopenia are physical activity and nutrition optimization. To make the greatest use of this knowledge, clinicians, nutritionists, and physical therapists alike must work together as a team to improve outcomes. Additionally, further research is warranted to investigate pharmacological approaches to treat sarcopenia, as they are currently unavailable.[94] [Level 4]

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Disclosure: Andrew Ardeljan declares no relevant financial relationships with ineligible companies.

Disclosure: Razvan Hurezeanu declares no relevant financial relationships with ineligible companies.