Sarcopenia

Anne Tournadre, Gaëlle Vial, Frédéric Capel, Martin Soubrier, Yves Boirie

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Anne Tournadre, Gaëlle Vial, Frédéric Capel, Martin Soubrier, Yves Boirie. Sarcopenia. Joint Bone
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Accepted Manuscript

Title: Sarcopenia

Authors: Anne Tournadre, Gaelle Vial, Frédéric Capel, Martin

Soubrier, Yves Boirie

PII: S1297-319X(18)30189-1
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Please cite this article as: Tournadre A, Vial G, Capel F, Soubrier M, Boirie Y,
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Sarcopenia

Anne Tournadre 1,3, Gaelle Vial1,3, Frédéric Capel3, Martin Soubrier1,3, Yves Boirie2,3

1
Service de rhumatologie, CHU Clermont-Ferrand, Hôpital G Montpied, 63003 Clermont-Ferrand,

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France
2
Service de nutrition clinique, CHU Clermont-Ferrand, Hôpital G Montpied, 63003 Clermont-

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Ferrand, France

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3
Unité de Nutrition Humaine, UMR1019 INRA/Université Clermont Auvergne, 63000 Clermont-

Ferrand, France

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Corresponding author
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Anne Tournadre, Service de Rhumatologie, Hôpital G Monpied, CHU, 58, rue Montalembert,
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63000 Clermont-Ferrand, France

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Tel. : +33 473 751 488

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E-mail: [email protected]
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Highlights
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 Sarcopenia is defined as loss of muscle mass combined with loss of muscle function and

alterations in muscle quality.

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 Age, mobility restrictions, muscular anabolic resistance and lipotoxicity, and inflammation

are the main mechanisms underlying sarcopenia.

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 Sarcopenia is associated with increased morbidity and mortality rates, notably in patients who

also have a high fat mass (sarcopenic obesity).

 The management of sarcopenia include a nutritional strategy targeting the quality of proteins

and fatty acids, physical exercise, and antiinflammatory medications; stimulants of muscle

anabolism are under evaluation.

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ABSTRACT

Sarcopenia is defined as a combination of low muscle mass with low muscle function. The term

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was first used to designate the loss of muscle mass and performance associated with aging. Now,

recognized causes of sarcopenia also include chronic disease, a physically inactive lifestyle, loss

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of mobility, and malnutrition. Sarcopenia should be differentiated from cachexia, which is
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characterized not only by low muscle mass but also by weight loss and anorexia. Sarcopenia results
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from complex and interdependent pathophysiological mechanisms that include aging, physical
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inactivity, neuromuscular compromise, resistance to postprandial anabolism, insulin resistance,

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lipotoxicity, endocrine factors, oxidative stress, mitochondrial dysfunction, and inflammation. The
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prevalence of sarcopenia ranges from 3% to 24% depending on the diagnostic criteria used and

increases with age. Among patients with rheumatoid arthritis 20% to 30% have sarcopenia, which
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correlates with disease severity. Sarcopenia exacts a heavy toll of functional impairment, metabolic
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disorders, morbidity, mortality, and healthcare costs. Thus, the consequences of sarcopenia include

disability, quality-of-life impairments, falls, osteoporosis, dyslipidemia, an increased

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cardiovascular risk, metabolic syndrome, and immunosuppression. The adverse effects of

sarcopenia are particularly great in patients with a high fat mass, a condition known as sarcopenic

obesity. The diagnosis of sarcopenia rests on muscle mass measurements and on functional tests

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that evaluate either muscle strength or physical performance (walking, balance). No specific

biomarkers have been identified to date. The management of sarcopenia requires a multimodal

approach combining a sufficient intake of high-quality protein and fatty acids, physical exercise,

and antiinflammatory medications. Selective androgen receptor modulators and anti-myostatin

antibodies are being evaluated as potential stimulators of muscle anabolism.

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Keywords: Sarcopenia. Muscle. Fat mass.

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Definition

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The term sarcopenia was initially used to designate age-related loss of muscle. However,
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the definition of sarcopenia now encompasses muscle loss related to chronic disease, physical
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inactivity or impaired mobility, and malnutrition. Although it has been suggested that age-related

primary sarcopenia could be differentiated from secondary sarcopenia due to a chronic disease or
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loss of mobility (1), this distinction is difficult to make in everyday practice, as older patients often
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have multiple comorbidities. Sarcopenia is defined as loss of muscle mass combined with
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alterations in physical function and muscle quality. These last two characteristics are strongly

associated with morbidity and mortality (2,3). Sarcopenia has been recognized as a disease by the
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World Health Organization and included in the International Classification of Diseases (ICD code

M62.8) (4).
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Cachexia is a complex multifactorial condition characterized by increased catabolic activity

during a severe chronic disease associated with high-grade inflammation. The manifestations of

cachexia include weight loss with loss of muscle mass and, often, of fat mass; metabolic disorders;

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and anorexia (5). This definition of cachexia, in which weight loss is the main criterion, is not met

in several chronic diseases such as rheumatoid arthritis (RA), during which the fat mass remains

unchanged or increases, thus potentially explaining the absence of weight loss despite the loss of

muscle mass (6). This clinical phenotype known as sarcopenic obesity implies a tight connection

between muscle and fat tissue. Sarcopenic obesity plays a central role in muscle function and

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quality impairments and in the development of cardiometabolic and bone disorders.

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Mechanisms

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The muscle is a biomechanical contractile organ that applies forces to bone, thereby allowing

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movement. In addition to this role in motricity, however, muscle is essential to metabolic
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homeostasis. Thus, muscle is a key player in glucose uptake, glycogen storage, lipid oxidation,
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amino acid release, and energy production. Furthermore, muscle is indirectly involved in the

immune response, as it serves as a reservoir of amino acids that are rapidly available to
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immunocompetent cells. The mechanisms responsible for sarcopenia are complex and
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interdependent (Figure 1).

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Age, physical inactivity, neuromuscular impairments

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Muscle mass declines with increasing age, chiefly at the expense of fast twitch type II fibers.

The median annual decrease in muscle mass over the lifespan is 0.37% in females and 0.45% in
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males. Data on the age at which the decline begins are conflicting. However, after 70 years of age

the annual decrease is 0.70% in females and 0.90% in males (7). The age-related loss of muscle

mass is due to a gradual decline in the synthesis of muscle proteins, including those present in the

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contractile apparatus and mitochondria, combined with impaired proteolysis control. The loss of

strength (dynapenia) occurs at a 2- to 5-fold faster rate compared to the loss of muscle mass (7).

This finding suggests that the ability of muscle to generate force (muscle quality) may undergo

early alterations due to changes in body composition and increases in fat mass (3).

Physical inactivity accelerates the loss of muscle mass and strength. During bed rest, 1 kg of

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muscle mass is lost after 10 days (8) and 9% of quadriceps strength after only 5 days, even in young

individuals (9). Neurological impairments that contribute to the loss of muscle include motor cortex

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atrophy, alterations in neurotransmitters, loss of fast twitch fibers leading to a predominance of

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slow twitch fibers, and loss of motor neurons responsible for motor unit loss and reorganization.

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Postprandial resistance to anabolism
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The decrease in the mass of muscle protein is the net result of an imbalance between protein
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synthesis (anabolism) and proteolysis (catabolism). Protein synthesis requires an adequate supply
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of amino acids from the diet or from proteolytic processes. Anabolism is triggered chiefly by the
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intracellular insulin signaling pathway and insulin-like growth factor-1 (IGF-1) receptor pathway
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(IGF-1/AKT/mTOR), which also inhibit proteolysis. Catabolism involves many specific

proteolytic pathways, including the ATP-dependent ubiquitin-proteasome complex, which is

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influenced by multiple factors (inadequate nutrient intake, physical inactivity, hormone

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deficiencies, and proinflammatory cytokines). The main finding from studies on this topic is that

aging is related, not to a basal disorder in protein renewal, but to a blunting of the anabolic response
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to food intake known as postprandial anabolic resistance (Figure 2). In the fasting state, the protein

balance is negative, since protein synthesis falls below protein catabolism. In contrast, after a meal

the protein balance normally becomes positive, as protein synthesis increases and proteolysis

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diminishes, particularly if the meal is high in protein. Aging is associated with impairments in the

ability to synthesize protein in response to various nutritional factors (dietary protein, amino acids,

insulin) (10). In vitro, stimulation of rat muscle protein synthesis to a predefined level requires

twice as much leucine in aged animals than in young animals (11). The result is a negative protein

balance with a steady decline in protein stores day after day.

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Insulin resistance and lipotoxicity, endocrine factors

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Insulin plays a major role in protein metabolism by stimulating amino acid transport within

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tissues, enhancing protein synthesis, and inhibiting proteolysis. However, the effects of insulin on

muscle seem diminished during aging and in obese patients with insulin resistance (12,13).

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Interestingly, muscle protein renewal correlates negatively with fat mass (13), suggesting an
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adverse effect of fat mass on muscle protein synthesis. The ectopic accumulation of toxic lipids
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(ceramides and diglycerides) within skeletal muscle promotes insulin resistance and muscle
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resistance to anabolism, a phenomenon known as muscle lipotoxicity (14). In aged animals, adipose
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tissue expansion and, therefore, fatty acid uptake by adipose tissue are decreased, resulting in
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ectopic accumulation of toxic lipids within the muscle (myosteatosis) (14).

In addition to insulin, other hormones are involved in muscle mass loss, notably sex
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hormones (testosterone, dehydroepiandrosterone), cortisol, vitamin D, growth hormone (GH),

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IGF-1, and myostatin. These hormones act on the activation and proliferation of muscle satellite

cells, adipogenesis, and proteolysis. However, the available data are fragmentary and difficult to
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reconcile given the wide variety of models and targets used in published studies.

Oxidative stress and mitochondrial dysfunction

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 Sarcopenia is associated with loss of muscle mitochondria and mitochondrial enzymes,

mitochondrial DNA mutations and, eventually, alterations in fatty acid beta-oxidation and in the

function of the mitochondrial respiratory chain that produces energy in the form of ATP. Together

with impairments in cellular antioxidant properties, this age-related mitochondrial dysfunction

contributes to the accumulation of reactive oxygen species (ROS), which alter the function of

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myofibrils, motor neurons, and the sarcoplasmic reticulum and impair muscle regeneration (7).

Increased ROS levels indicating exacerbated oxidative stress correlate with loss of handgrip

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strength in older women (7). The decline in mitochondrial oxidative capacity can also promote

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lipid accumulation within skeletal muscle even when the dietary fat intake remains unchanged.

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Inflammation
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Elevated levels of C-reactive protein, IL-6, and TNFα may promote muscle loss and are
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associated in older individuals with declines in muscle mass and muscle strength (15). IL-6
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overexpression in transgenic mice induces muscle wasting, which can be reversed by administering
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an IL-6 receptor antagonist (16). TNFα injection in mice activates the proteolytic pathways, notably
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those involving the proteasome, and impairs muscle function (17). In patients with RA, IL-6

inhibition by tocilizumab is associated with lean mass gains, whereas fat mass does not increase
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(18). The data on TNFα antagonists are less consistent (18).

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A single study assessed the anabolic muscle response after meals and after exercise (19). The

patients had RA without sarcopenia. No differences were found with matched controls (19). Insulin
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resistance is also associated with RA. Both proinflammatory cytokines (IL-6, TNFα) and

glucocorticoids promote insulin resistance in RA (20). Oxidative stress contributes to skeletal

muscle dysfunction in animal models of collagen-induced arthritis (21). Rats with collagen-induced

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arthritis exhibit protein metabolism alterations, fatty acid accumulation, and mitochondrial

dysfunction, as well as muscle wasting, supporting the hypothesis that joint inflammation is

associated with muscle lipotoxicity (22). Among hormonal factors, myostatin is regulated during

chronic inflammation and may therefore be involved in inflammatory sarcopenia via its catabolic

effects (23).

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Epidemiology and impact of sarcopenia on health

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The prevalence of sarcopenia varies across populations and according to the definitions and

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cutoffs used. Prevalences of 3% to 24% have thus been reported in individuals older than 65 years

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(24) (Table 1). Using the criteria and cutoffs defined by the European Working Group on
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Sarcopenia in Older People (EWGSOP) (25), the prevalence is 7.1% when both loss of muscle
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mass and loss of muscle function are required and 11% when only the muscle mass loss criterion

is required (24).
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Sarcopenia has major adverse effects on function, metabolism, morbidity, and mortality.
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Thus, sarcopenia is associated with functional disabilities, quality-of-life impairments, falls,

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osteoporosis, dyslipidemia, an increased cardiovascular risk, metabolic syndrome, and

immunosuppression. Both muscle mass and muscle function (strength, walking speed) are
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independently associated with mortality (2,26,27). Decreases in both muscle mass and muscle

function are associated with a 3.7-fold increase in mortality (26) and a 2-fold increase in the fall
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risk (24), as well as with a greater risk of dependency (28). Sarcopenia is associated with a 50%

increase in the risk of admission, a 20-day increase in hospital stay length, and a 34% to 58%

increase in hospital care costs (29,30).

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 About 20% to 30% of patients with RA have a decrease in muscle mass (18,31). Loss of

muscle mass correlates with disease severity, disease activity, and quality of life (32–34). Although

loss of mobility is usually ascribed to the joint involvement, it explains only 20% of the decrease

in walking speed. Body composition is the other major determinant (35). The alterations in walking

ability, quality of life, and self-sufficiency are even more marked in patients with sarcopenic

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obesity (28,34,35). Changes in the ratio of lean mass over fat mass are probably also involved in

the development of the cardiometabolic comorbidities seen in RA. Thus, a low body mass index

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(BMI) is associated with increases in the risks of cardiovascular disease (36) and metabolic

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syndrome, whereas the opposite is true in the general population (37). That muscle, fat, and bone

tissues are closely linked has been suggested for several years but remains controversial. In a

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prospective 3-year cohort study of 65-year-old retirees in Switzerland, sarcopenia was associated
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with a 2.3-fold increase in the risk of osteoporotic fracture after adjustment on age, gender, and the
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FRAX score (38). Nevertheless, in a cohort of women in the US, bone mineral density (BMD) was
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the main determinant of the fracture risk, which was not increased by the presence of sarcopenia
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(39). Muscle mass loss in patients with RA is associated with a BMD decrease at the hip but not
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with the fracture risk (40).

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Diagnosis
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The EWGSOP diagnostic criteria perform best in predicting the fall risk. Both muscle mass
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and muscle strength or physical performance must be measured (1,24,25) (Box 1).

Muscle mass can be estimated using a simple anthropometric method that consists in

computing the corrected arm muscle area after measuring the triceps skinfold thickness (41).

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Although few studies have assessed the performance and reproducibility of anthropometric

methods, the corrected arm muscle area performed better than BMI in predicting mortality (41).

Bioimpedance analysis (BIA) is an inexpensive alternative to dual-energy X-ray absorptiometry

(DXA) for obtaining an immediate measurement of lean mass but does not directly evaluate the

muscle and bone compartments. BIA values vary with the degree of hydration of the individual,

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have not been validated in patients with chronic diseases, and underestimate lean mass. DXA is

currently the investigation of reference for evaluating total body composition. DXA provides

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measurements of muscle mass, fat mass, and bone mass. DXA results can be used to compute the

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skeletal muscle mass index (SMI) by normalizing the lean mass of the four limbs to either height

(in Europe) (1,25) or BMI (in the US) (42). SMI cutoffs relative to a standard population have been

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determined for sarcopenia. Although DXA is the method of reference for accurately measuring
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body compartments and determining whether fat tissue is located in the subcutaneous or visceral
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compartment, it is a global, projected, two-dimensional technique that does not take into account
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any possible interactions among tissue types. Computed tomography (CT) of the lumbar spine with
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slices at the level of L3 followed by image analysis using dedicated software provides an estimate
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of lumbar skeletal muscle mass (psoas, rectus abdominis, external oblique, and paraspinal

muscles). Peripheral quantitative CT (pQCT) is a more recently developed tool that is used in
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clinical research. With pQCT, three-dimensional transverse slices can be obtained at all four limbs
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and used to assess bone mass, muscle mass, and muscle density in the same volume.

Handgrip strength is used as a measure of muscle strength. Available tools for assessing
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physical performance include walking speed measurement, the step-on-stool test, or the Short

Physical Performance Battery (SPPB) combining a measure of balance, walking speed, and the

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get-up-and-go test (25). A sarcopenia screening questionnaire (SARC-F) can be helpful in patients

older than 65 years (1).

A broad spectrum of phenotypes is associated with sarcopenia, ranging from loss of both

muscle mass and fat mass (cachexia and precachexia) to absence of weight loss or even weight

gain (sarcopenic obesity). Criteria for evaluating the severity of sarcopenia have been developed

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(25). Presarcopenia is characterized by low muscle mass that has no impact on muscle strength or

physical performance. Sarcopenia is defined as low muscle mass combined with loss of muscle

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strength or physical performance. Severe sarcopenia is low muscle mass with both low muscle

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strength and low physical performance. Obesity or sarcopenic obesity can be defined as low muscle

mass as assessed using DXA (SMI) combined with a fat mass greater than 28% in males and 40%

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in females. Sarcopenic obesity precedes and predicts loss of self-sufficiency, whereas neither
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obesity alone nor sarcopenia alone is independently associated with loss of self-sufficiency (28).
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Nevertheless, these methods are neither readily available in everyday practice nor reimbursed by
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the French statutory health system. Furthermore, they do not allow a noninvasive or minimally
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invasive assessment of fatty infiltrates within muscle tissue (1,25). This is regrettable, as muscle
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quality, which results from body composition, muscle function, and muscle fat content is a far

better marker of both loss of mobility and mortality (3). In oncology, muscle quality is recognized
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as a predictor of survival (43).

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The complex and multifactorial pathophysiology of sarcopenia is a major obstacle to

identifying a specific biomarker that would be easily available and would reflect both muscle mass
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and muscle function. The most widely cited markers reflect the level of inflammation and

nutritional status (hemoglobin, albumin, CRP, IL6, TNFα), oxidative stress (protein carbonylation,

oxidized LDL), and hormonal status (testosterone, IGF-1, DHEA, vitamin D). None of these

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markers is specific of sarcopenia. The serum creatinine level reflects the muscle mass in individuals

whose renal function is normal. A low serum creatinine level is associated with an increase in

mortality (44). Serum creatinine could be used in combination with another renal function marker,

cystatin, to define a sarcopenia index (44). Circulating free nucleic acids, procollagens, agrin,

myokines, and proteomic parameters are being evaluated as biomarkers for sarcopenia.

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MANAGEMENT OF SARCOPENIA

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A healthy diet and sufficient physical activity are the main determinants of energy

homeostasis and body composition changes. Inflammation, insulin resistance, and physical

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inactivity promote fat deposition, anabolic resistance, and lipotoxicity within the sarcopenic
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muscle. Sarcopenia therefore requires a multimodal management approach combining a nutritional
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strategy targeting nutrient quality and intake, exercise, and antiinflammatory and anabolic
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medications.
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Nutrition

In patients with age-related sarcopenia who are older than 65 years, the daily recommended
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protein intake is 1 to 1.2 g/kg/day instead of 0.8 g/kg/day (45). Protein supplements, notably
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essential amino acid supplements including leucine may benefit muscle mass and function,

although the benefits are inconsistent (46). The rates of digestion and absorption, the modalities of
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protein intake throughout the day, and the synergistic effects of protein with physical exercise or

other nutrients are key determinants of the effectiveness of the protein intake (47).

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 Vitamin D diminished lipotoxicity and exerted anabolic effects on muscle in animal studies

(48). In males older than 65 years, when used in combination with leucine-enriched whey protein

for 6 weeks, vitamin D supplementation increased both postprandial protein synthesis and muscle

mass (49). Supplemental n-3 polyunsaturated fatty acids (omega-3) or monounsaturated fatty acids

contributed to decrease insulin resistance and lipotoxicity (50); prevented fat mass increases; and

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improved protein anabolism, muscle mass, and muscle function (51).

Appetite stimulants have been tested more specifically in patients with cachexia. Examples

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include megestrol acetate, a progestin medication, which can be given alone or with L-carnitine;

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thalidomide, and ghrelin.

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Physical activity
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Even low-level physical activity induces decreases in the cardiovascular risk, insulin
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resistance, and mortality (52,53). Physical activity diminishes lipotoxicity by increasing
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mitochondrial fatty-acid beta-oxidation by muscle cells and increases the synthesis of muscle
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protein. Exercise benefits muscle strength and physical performance but does not consistently
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increase muscle mass (46). The optimal exercise modalities and the patient subgroups most likely

to benefit remain to be determined. Ideally, a physical training program should combine aerobic
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exercise to improve cardiovascular function and endurance and to decrease fat mass with strength
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exercises to increase muscle mass (54). In RA, physical exercise programs should be individually

tailored to disease stage, disease activity, and general health status. Intensive exercise programs
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designed to increase muscle mass and muscle strength often raise difficulties with implementation

and patient adherence.

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Biotherapies

The metabolic effects of cytokine antagonists, notably on muscle anabolism, remain

controversial and require further study. In several studies, TNFα antagonist or IL-6 antagonist

therapy was associated with weight gain in patients with RA or spondyloarthritis (SpA). Although

body composition changes have been documented in treated patients, few data are available on

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muscle strength and function, changes in energy expenditure and physical activity, and dietary

intakes. The data should therefore be interpreted with caution. Body composition does not seem to

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change in the short term in patients with RA treated with TNFα antagonists, although an increase

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in fat mass has been reported after 2 years of treatment (55–57). IL-6 antagonist therapy may hold

promise for the treatment of cachexia in patients with cancer (58). After 1 year of RA treatment

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with the IL-6 antagonist tocilizumab, patients had gained weight due to an increase in lean mass
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with no increase in fat mass but with a redistribution of adipose tissue toward the subcutaneous
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compartment (18). In patients with SpA, TNFα antagonist therapy may increase the fat mass and
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induce redistribution of adipose tissue toward the visceral compartment (57,59).

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Anabolic medications

Testosterone supplementation seems to have little efficacy in increasing muscle mass and is
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associated with adverse effects including cardiovascular events, prostate cancer, and virilization
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(60). Selective androgen receptor modulators (SARMs) exert anabolic effects on bone and muscle

but not on the other tissues. SARMs improved muscle mass and muscle function in phase II studies
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in older individuals and patients with cancer (61,62). Phase II studies of SARMs are ongoing

(NCT01355484). Estrogens have little effect, notably in women older than 60 years.

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 GH has produced disappointing effects in older patients. GH increases muscle mass but also

induces salt and water retention and fails to improve muscle strength (63). Creatine

supplementation has controversial effects. When combined with physical exercise, creatine

supplementation may improve both muscle mass and muscle strength (64). Myostatin regulates

muscle growth, and myostatin inhibition using a monoclonal antibody may constitute a targeted

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treatment for sarcopenia (65). A single monthly subcutaneous injection of myostatin inhibitor

improved muscle mass and decreased fat mass. Nevertheless, the effects on muscle function were

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discordant, and no improvements occurred in the 6-minute walking test, muscle strength, or the fall

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risk. Additional clinical trials are under way, notably with metformin (NCT02308228) and

angiotensin-converting enzyme inhibitors (ISRCTN90094835) in combination with either physical

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activity or leucine supplementation.
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Conclusion
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The introduction of biotherapies that target the inflammatory processes underlying chronic
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inflammatory joint disease has constituted a therapeutic breakthrough. Nevertheless, both RA and
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SpA remain associated with a decline in physical capabilities and with numerous comorbidities

responsible for both quality-of-life impairments and excess mortality. Body composition changes
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in these diseases, notably sarcopenic obesity, may contribute both to the functional disability and

to the increased risk of comorbidities. Preserving or improving muscle mass and function is
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therefore a key goal to maintain function and improve quality of life in patients with chronic

inflammatory joint disease. Achieving this goal will require investigations into the mechanisms

underlying sarcopenia in patients with inflammatory conditions and reduced mobility. In addition,

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readily available and noninvasive biomarkers are needed to ensure the early identification of

patients at high risk for sarcopenia. Treatment targets will need to be validated. Preventive and

curative strategies combining nutrition optimization, physical activity, and long-term targeted

medications will have to be developed. The recommendations and diagnostic tools discussed in

this article apply to age-related sarcopenia. These data must now be validated in patients with

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chronic inflammatory joint disease in order to establish decision algorithms and clinical practice

guidelines for identifying, preventing, or delaying the onset of sarcopenia.

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Disclosure of interests

None of the authors has any conflicts of interest to declare.

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Box 1

Criteria for the diagnosis of sarcopenia (EWGSOP) (1)

Low muscle mass

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- Anthropometry

Arm muscle area ≤21.4 cm2 in males, ≤21.6 cm2 in females

RI
- Bioimpedance analysis

SC
SMI <8.87 Kg/m2 in males, <6.42 Kg/m2 in females

FFMI ≤17 Kg/m2 in males, ≤15 Kg/m2 in females

U
- Computed tomography at L3
N
Lumbar SMI <55 cm2/m2 in males, <39 cm2/m2 in females
A
- Dual-energy X-ray absorptiometry (DXA)
M

Appendicular SMI <7.26 Kg/m2 in males, < 5.45 Kg/m2 in females

D

Low muscle strength

TE

- Handgrip strength: varies with BMI and gender

Males: BMI≤24, 29 Kg; 24<BMI≤28, 30 Kg; BMI ≥29, 32 Kg

EP

Females: BMI ≤23, 17 Kg; 23<BMI≤26, 17.3 Kg; 26<BMI≤29, 18 Kg; BMI >29, 21 Kg
CC

Low physical performance

- usual gait speed (<0.8 m/s)

A

- timed get-up-and-go test >10 s

- Short Physical Performance Battery (SPPB)

25
* EWGSOP defines sarcopenia as at least one muscle mass criterion plus at least one muscle strength or

physical performance criterion. SMI, skeletal muscle mass index; FFMI, fat-free mass index

PT
RI
SC
U
N
A
M
D
TE
EP
CC
A

26
Figure 1. Mechanisms underlying sarcopenia

PT
RI
SC
U
N
Figure 2. The postprandial anabolic resistance concept: the postprandial anabolic peak pic is
A
blunted in patients with anabolic resistance, resulting in a negative protein balance
M
D
TE
EP
CC
A

27
Table 1. Criteria and cutoffs used to diagnose sarcopenia
Sarcopenia
ESPEN
EWGSOP IWGS with limited FNIH
SIG
mobility
MUSCLE MASS
2 2 2
DXA SMI kg/m SMI kg/m SMI kg/m LMApp kg
≤7.26 (M) LM total Kg ≤7.23 (M) ≤6.81 (M) <19.75 (M)
≤5.54 (F) ≤5.67 (F) ≤5.18 (F) <15.02 (F)

PT
LMApp /BMI
<0.789 (M)
<0.512 (F)

RI
FONCTION MUSCULAIRE
Handgrip Kg BMI <26 kg (M)
<16 kg (F)

SC
kg/BMI
<1 (M)
<0.56 (F)

U
Walking speed < 0.8 m/s < 0.8 m/s < 1 m/s < 1 m/s
6MWT< 400 m
Timed get-up-and- >10 s
go test
N
A
M

EWGSOP: European Working Group on Sarcopenia in Older People (Cruz-Jentoft et al., 2010)

ESPEN SIG: Special Interest Group “cachexia anorexia in chronic wasting diseases” (Muscaritoli et al., 2010)
D

IWGS: International Working Group on Sarcopenia (Fielding et al., 2011)

TE

Sarcopenia with limited mobility: Society for Sarcopenia Cachexia and Wasting Disorders (Morley et al., 2011)

FNIH Sarcopenia project (Studenski et al., 2014)

EP

LM, lean mass; App, appendicular; SMI, skeletal muscle mass index; BMI, body mass index; 6MWT, 6-minute

walking test; M, male; F, female

CC
A

28