“Sarcopenia Abordaje nutricional y terapia física para el adulto mayor”

Dra. Isabel Barrientos Calvo

Geriatría y Gerontología

Máster en nutrición para la promoción de la salud

Conflictos de interés

ABBOTT•

Guía

Reconocimiento de la sarcopeniaDefinición e Importancia clínicaEpidemiología

Herramientas diagnósticas

Abordaje de sarcopeniaNutricionalTerapia física

Conclusiones

Actualidad en sarcopenia

Evolución en la definición de sarcopenia

1989: IrwinRosenberg

2010: EWGSOP (EUGMS, ESPEN,

IAGG-ER)

2012-2013: SIG y ESPEN

Pérdida progresiva y generalizada de la masa y fuerza muscular esquelética con un riesgo de

discapacidad física, mala calidad de la vida y muerte

Disminución de masa muscular conel envejecimiento

Descenso de masa muscular y su función

debido a la edad, enfermedades crónicas

(incluído el cáncer), ingesta de proteínas y la

inactividad física

Cruz-Jentoft y col, Age and Ageing,2010Coker R y Wolfe R, 2012)

Stenholm y col, 2010Hao, Y.y cols. (2011) Am J Physiol Regul Integr Comp Physiol 301: R701–R715.

Biolo, G. Clinical Nutrition 33 (2014) 737e748

MÚSCULO

HUESO

SARCOPENIAOSTEOSARCOPENIA1

Fragilidad

La fragilidad describe a individuos con mínima resilenciaa la injuria y baja reserva fisiológica

NATURE REVIEWS | CLINICAL ONCOLOGY VOLUME 10 | FEBRUARY 2013 | 93

identity of the inflammation mediators participating in

cancer cachexia is emerging.35,36 In the brain, injection of

IL-1 elicits a rapid induction of muscle catabolism and

atrophy gene expression.36 Inflammation in muscle might

induce expression of molecules involved in leukocyte

trafficking, such as P-selectin glycoprotein ligand 1, as

an early event in the catabolic response.36 Indeed, patients

with cancer who have a single nucleotide polymorphism

associated with a low expression of the gene that codes for

P-selectin glycoprotein ligand 1 (SELPLG) have a reduced

likelihood of developing cancer cachexia than those with

the more-common genotype.37 The physiology of differ-

ent organs and tissues are carefully integrated, and, in

the past year, evidence from a murine knockout model

has suggested that fat–muscle crosstalk might be a criti-

cal regulator in the development of cachexia.38 A goal

of anorexia–cachexia therapy is to interfere with these

responses to inflammation: to restore positive energy

balance and to promote the gain of skeletal muscle mass.

Understanding the specific management of the initiating

inflammatory pathways is crucial to that end.

Catabolism

In patients with cancer, a number of factors increase the

catabolic response, leading to unsustainable levels of fat

and muscle mobilization and levels of muscle depletion

that cause significant morbidity and mortality. These

factors include tumour progression, comorbid condi-

tions, old age, physical deconditioning, nutritional defi-

ciency, drugs and medical interventions.6 Tumours alter

energy regulation by eliciting an excessive inflammatory

response, which will augment both central and peri-

pherally mediated catabolic events.32 There is also direct

macronutrient consumption by the tumour. In late-stage

disease, when the overall tumour mass reaches >0.75 kg,

the energy consumption of the tumour is quanti tatively

important. It has been estimated in metastatic colorectal

cancer that increases in visceral organ mass and tumour

mass represented a cumulative incremental resting

energy expenditure of ~17,700 kcal over a time period of

3 months, and as such might contribute substantially to

cachexia-associated weight loss.19

Owing to their age and overall health status, patients

with cancer are prone to physical deconditioning and to

nutritional deficits.6 Inactivity causes muscle wasting

per se, potentiates catabolic signals and desensitizes

muscle to anabolic signals; for example, 10 days of bed

rest in otherwise healthy adults over 65 years of age

results in a 6% loss of muscle in the lower limb, 30%

reduction in muscle protein synthesis and 16% loss of

isokinetic strength.39 Bed rest also increases the catabolic

response of skeletal muscle to low doses of cortisol by

threefold in humans.40 This finding might be an especi-

ally important problem because the muscle protein cata-

bolic response initiated in the brain by inflammation is

mediated by cortisol.36

The role of malnutrition in promoting and exacer-

bating cancer cachexia is not fully understood. One

theme in the clinical literature is the importance of treat-

able causes of reduced food intake. Some data suggest a

gross deficiency of essential nutrients in patients with

cancer; one good example is a deficiency of long chain

n-3 polyunsaturated fatty acids.41 Specific supplemen-

tation with these fatty acids limited catabolic losses of

skeletal muscle in patients with lung cancer undergoing

chemotherapy.42,43 Further work is required with respect

to other classes of essential nutrients that might be defici-

ent in patients with cancer, including—but not limited

to—vitamin D and choline.44,45

Several drugs used to treat patients with cancer add to

the risk of muscle wasting (Figure 5). The best-known

culprits are high-dose corticosteroids (which induce a

Cushing’s-like muscle wasting and insulin resistance).46

No treatment is generally provided to offset the cata-

bolic effects of corticosteroids, even though agents such

as oxandrolone have demonstrated clinical efficacy in

this regard.47,48 Cancer therapy is increasingly targeted

against molecular pathways that are responsible for

tumour cell proliferation, such as the PI3K, AKT, and

mTOR pathways that are associated with cancer initia-

tion and are also involved in activating muscle protein

anabolism.49–51 It would be reasonable to anticipate that

muscle wasting would be a significant toxicity of drugs

that target these pathways.

Outcomes of cachexia therapyUnfortunately, cachexia is rarely managed actively, in

part owing to a lack of knowledge about clinical nutri-

tion in the oncology field,52 but also because of a lack of

0 25 50 75

Muscularity (rank)

Haz

ard

ratio

for d

eath

100

0

3.5

2.5

1.5

0.5

4.5

Least Most

Threshold for increasedhealth risk

Figure 3 | Threshold definition for sarcopenia: a low level

of muscle, characterized by a statistically significant

increase in health risk. Muscularity (that is, muscle mass

adjusted for stature) has a sex-specific range in any given

population. When studied as a continuous variable, high

muscularity has the lowest risk of death, with progressively

increasing risk of death with decreasing muscularity.

A statistical test for a threshold value (that is, optimal

stratification) can be used to define a cut-off point for the

definition of sarcopenia. Health risks associated with

decreased muscularity include mortality, treatment toxicity,

infection and physical disability.

FOCUS ON PALLIATIVE CARE

© 2013 Macmillan Publishers Limited. All rights reserved

Curr Opin Clin Nutr Metab Care 2017, 20:498–503

PLoS One. 2017 Jan 17;12(1):e0169548

Pérdida funcional•Alto riesgo de discapacidad OR • 3.03 (95% CI 1.80–5.12)

Caídas•Riesgo recurrente de caídas (al menos • 2/a) OR 2.38 (95%CI 1.75–3.23)

Fracturas•Hombres • 3.75 (95% CI 2.64–5.32) Mujeres• 2.8 (95% CI 1.72–4.58)

Hospitalización•HR • 1.57 (95% CI 1.03–2.41)

Estancia • hospitalariaOR • 1.84 (95%CI 1.32–2.58Sarcopénico• 19.5 ± 16.3 días vs no sarcopénico 15.0 ± 9.9 días

Mortalidad: • OR 4.42 (95% CI 3.60–5.42)

Actor Principal en sarcopenia

Función motora

JAMDA 17 (2016) 789e796Nutr Hosp. 2015;32(3):977-985

Nutrients 2018, 10, 391

Función metabólica

Prevalencia

Cooker y Wolf (2012):1,2

• 5-13% entre los 60-70 años

68• % en población institucionalizada.

Por medio de DXA:2,3

13• -24% entre los 65 y 70 años

Mayor• del 50% en personas mayores de 80 años.

1. Coker R. Y Wolfe R. (2012) . Current Opinion Clinical Nutrition and Metabolism Care. 15:7-112. Burgos R. (2006) Endocrinología Nutricional;53(5):335-44

3. Velázquez M y Irigoyen M. (2011). Revista de Ciencias Clínicas Vol. 12, Núm. 1 pp. 22-334. Curr Opin Clin Nutr Metab Care 2017, 20:498–503

Journal of the College of Physicians and Surgeons 2018, Vol. 28 (8): 586-588 Figura tomada de JAMDA 17 (2016) 675e677

En Costa Rica: CRELES• 1

Criterios de EWSOP: •

10,26• % de las personas estudiadas (33.2% entre 70-79 años y un 43,5% en los mayores de 80 años)

• Mujeres (63,4%) y hombres (36,6%)

Barrientos1. -Calvo I y Picado-Ovares E. Datos no publicados.4. Curr Opin Clin Nutr Metab Care 2013, 16:83 – 88

Se estima el número de individuos con sarcopenia 19 740 527 en el 2016 a32 338 990 en 2045 (incremento del 63.8%).

Qué propicia el descenso de masa muscular?

Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 190–201 2. J Nutr Health Aging. 2017;21(4):449-456

DM

Afectan la síntesis, proteólisis, la integridad del músculo2Qué factores pueden tener en común?

Infiltración• intramiocelular de grasa: Mayor pérdida de fuerzamuscular (30%) en extremidades inferiores

1 Calcif Tissue Int. 2015 Oct;97(4):385-90Curr Opin Clin Nutr Metab Care 2013, 16:83 – 88

Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 69–77Imagen tomada de: Am J Physiol Regul Integr Comp Physiol. 2018 Sep 1;315(3):R461-R468

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Joven Adulto mayor

Incremento en la expresión de miostatina.• 1

Miembro de la • superfamilia TGF-b

Impacto en crecimiento y desarrollo de músculo esquelético•

Descrita en • 1997

Exp Clin Endocrinol Diabetes. 2018 Aug 3. doi: 10.1055/a-0641-5546 PLoS One 2012; 7:e37236

Curr Opin Clin Nutr Metab Care 2013, 16:83 – 884 Physiol Rev 98: 2133–2223, 2018

Resistencia a la insulina• 4

4 Physiol Rev 98: 2133–2223, 2018

Inhibición del Receptor

Sobrepeso y obesidad•

Curr Opin Clin Nutr Metab Care 2013, 16:83 – 88

P < 0.05 type 2 diabetic versus lean patients

Diabetes (2015) 9:64

Sobreproducidas en DM y obesidad visceral

Baja actividad física•

Cambios en el tipo de fibra muscular•

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Am J Physiol Regul Integr Comp Physiol. 2018 Sep 1;315(3):R461-R468

Envejecimiento Cambios hormonales•

Testosterona•

GH•

IGF• -1

Vitamina D•Descripción de miopatía proximal tan incapacitante como tener que usar silla •de ruedas en AM con valores < 20 nmol/l1

Estudios epidemiológicos asociación entre vitamina D e incidencia de •sarcopenia3

Disminución en la expresión del receptor de • vit. D.Deficiencia favorece la • adipogénesis MO e intramuscular, lo cual reduce la actividad contráctil muscular.2

Bone1. Reports (2018) 9:120-121Curr2. Opin Clin Nutr Metab Care 2017, 20:498–503

3. J Gerontol A Biol Sci Med Sci 2017

1. Healthcare 2015, 3, 529-543

Estudio ABC: Houston D y cols. (2008) Am J Clin Nutr;87:150–5Diabetes Metab Res Rev. 2015 Sep;31(6):545-61.

Baja ingesta proteica y alta en grasas

Dra Barrientos C.

This article is protected by copyright. All rights reserved.

Figure 2: Mechanisms involved in low-grade inflammation induced by high fat diet

on epithelial intestinal barrier.

The role of commensal enteric bacteria in diet-induced adiposity and systemic

inflammation may be essential to induce intestinal inflammation and weight gain. Long-

term ingestion of HFD in mice or in obese mouse model (ob/ob) altered gut bacterial

composition, increasing the abundance of Firmicutes and Enterobacteriaceae (LPS-

bearing species) with a proportional reduction in Bacteroidetes phylum as well as an

overall lower bacterial diversity. Such increases of these species may be secondary to

compromised production of mucus or antimicrobial components or their survival of

intestinal Paneth cells in response to HFD, favoring thus bacterial survival and adherence

to the epithelium. Bacteria can cross the mucus layer and reach the epithelial barrier. HFD

were shown to promote colonic inflammation through induction of TLR4 on epithelial

cells and macrophages. This allows the production of several inflammatory cytokines

(TNF-α, IL-6, IL-1β, iNOS, COX-2 and myeloperoxidase activity, etc), which promptly

mediate vascular changes to promote immune cell recruitment against invading

pathogens, initiating the inflammatory state. Saturated fatty acids (SFA) can also increase

inflammation. A down-modulation of IL-10 producing Tregs cells in obesity decrease the

antioxidant enzymes leading to increase of reactive oxygen species (ROS) production.

HFD and obesity were also reported to downregulate anti-inflammatory gut peptide

secretion (e.g. ghrelin, GLP-1, PYY, CCK) by enteroendocrine cells and/or by signalling

further amplification of HFD-induced intestinal inflammation. In addition, with

downregulation of anti-inflammatory gut peptides associated with HFD or obesity, diet-

induced obesity can also enhance the secretion of pro-inflammatory serotonin (5-HT) by

enterochromaffin cells in the ileum. Collectively, these findings support the hypothesis

that, in response to HFD, the early activation of intestinal inflammation is a cornerstone

in the establishment of a low-grade systemic inflammation and ensuing metabolic

disorders.

This article is protected by copyright. All rights reserved.

Figure 3: HFD and transit of bacterial components to blood, adipose and skeletal

muscle cells leading to systemic low grade inflammation.

Obesity is associated with a low-grade systemic pro-inflammatory state that promotes the

development of metabolic disorders. In addition to expected changes in gut microbiota

(gastrointestinal tract: step 1) and adiposity, mice chronically-fed with HFD had higher

and constant circulating levels of LPS (about 2-3 fold the levels in LFD-fed mice) termed

“metabolic endotoxemia’’ as a low but chronic increase of systemic LPS. Association of

HFD-induced endotoxemia with systemic inflammation is reflected by increased

expression of TLRs in circulating macrophages cells, and plasma TNF-α and IL-1β

(blood: step 2). Greater systemic inflammation in individuals with metabolic diseases

may be a direct consequence of LPS-induced excessive inflammatory mediators and

peripheral tissue resident inflammatory cells through interaction with the TLR4. HFD via

endogeneous SFA may contribute to the activation of TLR2 or TLR4. Activated

inflammatory macrophages (M1) may reach adipose and muscular tissues (step 3). Under

normal circumstances, lean adipose tissue resident macrophages adopt a M2 phenotype

characterized by secretion of anti-inflammatory IL-10. In diet-induced obesity, the M1

pro-inflammatory phenotype predominates in adipose tissue and this switch may be

mediated, in part, by interaction of SFAs and LPS with macrophages. Adipocytes

themselves may also contribute to inflammation in secreting inflammatory cytokines in a

TLR-dependent manner in response to LPS and/or SFAs. Once initiated, this

inflammatory environment may recruit new inflammatory cells (neutrophils,

macrophages) thus amplifying inflammatory response in adipose tissue.

USA 38% AM hombres y 41% AM mujeres consumen menos del

requerimiento diario de proteína 1

Menos AA al músculo

Sarcopenia

Ya conocemos la definición• …

Datos epidemiológicos•

Conocemos los factores que inciden en su desarrollo• …

Cómo lo diagnosticamos?•

Debe haber medición de:

• 1. Masa muscular

• 2. Función muscularFuerza muscular•

Desempeño físico•

Dra. I Barrientos

Identificación de sarcopenia-Masa muscular-

Tomografía• Computarizada

Resonancia• Magnética

Absorciometr• ía radiológica de doble energía (DEXA):

Índice• de Músculo Esquelético Apendicular

Bioimpedancia• (BIA)

Índice• muesculoesquelético (SMI)

Antropometría•

Ultrasonido•

Age and Ageing 2010; 39: 412–423

Curr Opin Clin Nutr Metab Care 2016, 19:125 – 130

Curr Opin Crit Care 2017, 23:000 – 000

Nutr Hosp. 2015;32(3):977-985

Dual-energy X-ray absorptiometry

Nutr Hosp. 2015;32(3):977-985

Técnica no invasiva, fácilmente aplicable y con un nivel de radiación baja (<0.1 μGy)

Mide diferentes componentes por separado

Correlaciones con la RMN y la CT

Desventajas: Dificultad de medición en personas con una altura mayor de 190 cm Baja fiabilidad en personas con un peso inferior a 40 kg Las actualizaciones de los softwares

Bioimpedancia eléctrica

Nutr Hosp. 2015;32(3):977-985

Ventajas: no invasivo, relativamente barato, la evaluaciónpresenta un bajo coste, fácil aplicación

Utilizado en grupos poblacionales más grandes y/o en estudiosepidemiológicos

4 Journal of Parenteral and Enteral Nutrition XX(X)

monitor changes in body composition over time in certain

groups of pediatric patients.

Both upper and lower body muscle wasting has been

reported in critically ill children,3 and some adult data suggest

that muscle wasting affects lower limbs more than upper

limbs.28 However, ultrasound studies measuring thickness of

the biceps, forearm, and quadriceps in critically ill adults have

only described changes in average or total muscle thickness

instead of thickness of individual muscles.29,30 The quadriceps

alone has also been used to monitor muscle changes in critically

ill adults. Measurements of the thickness of the rectus femoris,

vastus intermedius, and vastus lateralis and cross-sectional area

(CSA) of the rectus femoris on alternate days demonstrate an

overall decreasing trend in the first 10 days of critical illness. 2,8

The quadriceps is the most commonly studied lower limb mus-

cle in children, of which the rectus femoris appears to be easier

to visualize than the vastus intermedius in severe muscle dis-

ease due to the attenuation of ultrasound waves reaching lower

muscle layers by overlying abnormal muscle. 10,15

Together, these data suggest that in critically ill children,

longitudinal measurements would be necessary to capture mus-

cle change throughout the ICU stay, possibly in more than 1

limb. Considering that critically ill children are usually sedated

and supine, ultrasound of the anterior compartment muscles

such as the quadriceps, biceps, and forearms is likely easier

than posterior compartment muscles such as the gastrocnemius

and triceps. However, if only a single limb measurement is pos-

sible, that of the quadriceps may be suitable.

Measurement Techniques

Several measurement techniques have been used in muscle

ultrasonography, although most emphasize consistent trans-

ducer settings and placement, body site, and subject position-

ing between patients and time period.16 Two-dimensional

B-mode ultrasound scans are usually conducted using a linear

transducer ranging from 5–12 MHz14,16,17 at a frequency of 25

Hz.17,31 Gain (ie, intensity or brightness) settings range from

70–86 dB,15,16 and depth is adjusted to visualize the bone

depending on the age of the patient.17

Quadriceps measurements are commonly taken at the mid-

point of the anterior superior iliac spine to the superior aspect of

the patella,15,16 although adult studies have used two-thirds the

distance from the anterior superior iliac spine.2,8 The latter

allows visualization of the entire muscle in adults and larger

children, which is necessary for measuring rectus femoris CSA.

For the other muscles, ultrasound measurements have been

taken at varying distances along the limb, and there appears to

be little standardization.19,20 In children with dynamic growth,

ultrasound landmarks using proportions of total limb length

instead of absolute distance may be more appropriate, so as to

account for varying changes in limb length.

Recommended patient positioning varies for different mus-

cle groups.32 The patient is usually positioned prone or supine

or, for some young children, sitting in their caregiver’s lap.24,33

The leg may be flat and relaxed16 or partially flexed,33 while

upper limbs are allowed to relax by the side of the body.32 The

transducer is placed perpendicular to the long axis of the mus-

cle to be measured, with the probe angled to optimize bone

echo.15 A generous amount of contact gel is used to minimize

compression of the subcutaneous tissue and muscle.23 Still

transverse images are taken (Figure 1), usually in triplicate,

and MLT or CSA is measured using electronic calipers.10,34

Patient cooperation is also necessary in children who are con-

scious; otherwise, MLT is likely to be inaccurately increased

with contraction in children who are not relaxed. 23

Time Course

The timing of measurement would depend on the sensitivity of

ultrasound in detecting changes in muscle size and echo-

genicity over time. Adult protocols specify measurements

every 1–3 days within the first 5–10 days of ICU admission to

be able to capture acute muscle changes within the initial

stages of critical illness,2,8,29,30 but whether this appropriately

captures muscle changes in children needs to be explored as

children may experience different metabolic responses from

adults.35–37 Standardization of these parameters would also

help with reproducibility and comparison across studies.

Reliability and Validity

Reliability

Ultrasound MLT and CSA of the lower limbs have been shown

to have good intraobserver reliability in healthy children and

children with cerebral palsy (CP), with intraclass correlation

coefficients (ICCs) of approximately 0.93–0.99 in children

Figure 1. Ultrasound image of the quadriceps muscles.

Ultrasonido

Puede proporcionar información sobre la arquitecturamuscular incluyendo el ángulo en el que se colocan lasfibras musculares y estructuras fasciculares.

Desventaja: Faltan estudios epidemiológicos

Nutr Hosp. 2015;32(3):977-985

Antropometría

Limitada precisión •

IMC: útil para estudios poblacionales, pero no diferencia la composición corporal• 1

1. Clin Nutr ESPEN. 2018 Jun;25:114-1202. Curr Opin Clin Nutr Metab Care 2016, 19:125 – 130

En este caso son 3 mujeres con baja masa muscular2

TC <38.9cm2/m2

Masa Muscular-AntropometríaCircunferencia de pantorrilla

Punto de corte 31 cm para PAM

Puntos de corte

JPEN J Parenter Enteral Nutr. 2015;39:787-822

No hay parámetros de puntos de corte para CR

Geriatr Phys Ther 2015;38:148–153Curr Osteoporos Rep. 2015 Aug;13(4):235

Dra. I Barrientos

Segundo parámetroFuerza Muscular-

Puntos de corte (PAM): Depende de la fuente utilizada

Frailty Study in Brazilian Older people (FIBRA Study) ≤ 25.8 kg en hombre y ≤ 17.4 kg en mujeres

EWSOP

FNIH

Dra. I BarrientosCurr Osteoporos Rep. 2015 Aug;13(4):235

Fuerza muscular

Age and Ageing 2010; 39: 412–423European Geriatric Medicine 2012; 3:157–160

Tercer parámetro-Desempeño físico-SPPB Total 12 puntos

Velocidad de marcha6 metros: 0.8 m/s

Diagnóstico de Sarcopenia: Hasta la fecha

TomografíaComputarizada

Resonancia magnética

Absorciometríaradiológica de dobleenergía (DEXA): Índice deMúsculo EsqueléticoApendicular

Bioimpedancia: Índicemuesculoesquelético(SMI)

Medida de la fuerza deprensión (hand-grip)

Flexoextensión de larodilla (uso eninvestigación)

Batería Breve de Rendimiento (SPPB) (para investigación)

Velocidad de marcha

Prueba de potencia de subir escalera

Prueba de levántese y camine

Baja Masa MuscularBajo Desempeño

FísicoBaja Fuerza Muscular

Age and Ageing 2010; 39: 412–423Yang M y cols. JAMDA. 2018 Mar;19(3):277.e1-277

Tratamiento de Sarcopenia

Nutrición-Metabólica

Intervención físicaRehabilitación Ejercicio