SARCOPENIA: Concepto y desarrollo A. López Soto Unidad de Geriatría Servicio de Medicina Interna Hospital Clínico de Barcelona

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

Definición de sarcopenia Problema médico aún mal definido. Algunos autores la consideran como un nuevo “síndrome geriátrico”. Sarco: músculo + Penia: pérdida

Age and Ageing 2010; 39: 412–423

Clasificación de la sarcopenia

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

Síntesis y degradación proteica muscular Simplified cellular pathways for muscle protein synthesis and degradation. Blue: synthesis pathways. Red: proteolytic pathways. Dotted lines: pathways that are not well characterized. Anabolic signals ac- tivate the phosphatidylinositol 3-kinase (PI-3K)/Akt/mTOR pathway, resulting in protein synthesis. Inactivity and inflamma- tory cytokines result in activation of NF- κB- and Fox-O-mediated induction of genes, resulting in muscle atrophy. Fox-O activates transcription of ubiquitin protea- some ligases, resulting in protein degrada- tion. PI-3K/Akt phosphorylates Fox-O, preventing its nuclear translocation and in- hibiting its activity. Fox-O, when active, can inhibit the mTOR pathway. Also, mTOR pathway activation inhibits protein degradation by lysosomal caspases. Myo- statin causes muscle atrophy via activating Fox-O and inhibiting PI-3K. BCAA = Branched-chain amino acids.

Músculo sarcopénico Figure 1: (a) In young muscle, abundant serum IGF-I can stimulate protein synthesis by activating Akt/mTOR/p70S6K pathway. Akt blocks the nuclear translocation of FOXO to inhibit the expression of Atrogin-1 and MuRF and the consequent protein degradation. Abundant serum GH, which is induced by ghrelin, activates JAK2-STAT5 signaling to promote muscle-specific gene transcription necessary to hypertrophy. In young muscle, testosterone and estrogen bind these intramuscular receptors (androgen receptor and estrogen receptor (α and β)), and activatemTOR and Akt, respectively. Lower serumamount ofmyostatin and TNF-α failed to activate signaling candidates (Smad 2/3, NF-κB, etc.) enhancing protein degradation. (b) In sarcopenic muscle, myostatin signals through the activin receptor IIB (ActRIIB), ALK4/5 heterodimer seems to activate Smad2/3 and blocking of MyoD transactivation in an autoregulatory feedback loop. Abundant activated Smad2/3 inhibit protein synthesis probably due to blocking the functional role of Akt. The increased blood TNF-α elevates the protein degradation through IKK/NF-κB signaling and enhance an apoptosis. Lower serum amount of IGF-I, GH, and anabolic hormones (testosterone and estrogen) failed to activate signaling candidates (Akt, mTOR, STAT5, etc.) enhancing protein synthesis. The impaired regulation of FOXO by Akt results in abundant expression of Atrogin-1 and MuRF and the consequent protein degradation in sarcopenic muscle.

Fisiopatología de la sarcopenia

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

5036 p >65 años BIA 8 años de follow up OBJECTIVES: To examine the temporal relationship between sarcopenia and disability in elderly men and women. DESIGN: Cardiovascular Health Study, a longitudinal study of cardiovascular disease and its risk factors in older people. SETTING: Four U.S. communities. PARTICIPANTS: Five thousand thirty-six men and women aged 65 and older. MEASUREMENTS: Whole-body skeletal muscle mass was measured at baseline, and subjects were classified as having normal muscle mass, moderate sarcopenia, or severe sarcopenia based on previously established thresholds. Disability was measured via questionnaire at baseline in up to eight annual follow-up examinations. The cross-sectional relationship between sarcopenia and prevalent disability at baseline was examined using logistic regression models. The longitudinal relation between sarcopenia and incident disability over 8 years of follow-up was examined using Cox proportional hazards models. RESULTS: At baseline, the likelihood of disability was 79% greater in those with severe sarcopenia (Po.001) but was not significantly greater in those with moderate sarcopenia (P5.38) than in those with normal muscle mass. During the 8-year follow-up, the risk of developing disability was 27% greater in those with severe sarcopenia (P5.006) but was not statistically greater in those with moderate sarcopenia (P5.23) than in those with normal muscle mass. CONCLUSION: Severe sarcopenia was a modest independent risk factor for the development of physical disability. The effect of sarcopenia on disability was considerably smaller in the longitudinal analysis than in the cross-sectional analysis. J Am Geriatr Soc 54:56–62, 2006.

170p > 80a MM por TAC Background. With the increasing aging population, the number of very elderly patients (age $80 years) undergoing emergency operations is increasing. Evaluating patient-specific risk factors for postoperative morbidity and mortality in the acute care surgery setting is crucial to improving outcomes. We hypothesize that sarcopenia, a severe depletion of skeletal muscles, is a predictor of morbidity and mortality in very elderly patients undergoing emergency surgery. Methods. A total of 170 patients older than the age of 80 underwent emergency surgery between 2008 and 2010 at a tertiary care facility; 100 of these patients had abdominal computed tomography images within 30 days of the operation that were adequate for the assessment of sarcopenia. The impact of sarcopenia on the operative outcomes was evaluated using both univariate and multivariate analysis. Results. The mean patient age was 84 years, with an in-hospital mortality of 18%. Sarcopenia was present in 73% of patients. More sarcopenic patients had postoperative complications (45% sarcopenic versus 15% nonsarcopenic, P = .005) and more died in hospital (23 vs 4%, P = .037). There were no differences in duration of stay or requirement for intensive care unit postoperatively. After we controlled for confounding factors, increasing skeletal muscle index (per incremental cm2/m2) was associated with decreased in-hospital mortality (odds ratio ;0.834, 95% confidence interval 0.731–0.952, P = .007) in multivariate analysis. Conclusion. Sarcopenia was independently predictive of greater complication rates, discharge disposition, and in-hospital mortality in the very elderly emergency surgery population. Using sarcopenia as an objective tool to identify high-risk patients would be beneficial in developing tailored preventative strategies and potentially resource allocation in the future. (Surgery 2014;156:521-7.)

CH CPH Figure 2 Kaplan-Meier curve indicating the survival of patients with cirrhosis (A) and patients with cirrhosis and hepatocellular carcinoma (B). A: Kaplan- Meier curve indicating the survival of cirrhotic patients with and without sarcopenia. The 6-m probability of survival was 71% and 90%, respectively (P = 0.005, Log- Rank test); B: Kaplan-Meier curve indicating the survival of patients with cirrhosis and hepatocellular carcinoma with and without sarcopenia. The 6-mo probability of survival was 67% and 90%, respectively (P = 0.003, Log-Rank test).

3659 p en 2004 (1988-1994) MMT por BIA BJECTIVE: Obesity (as defined by body mass index) has not been associated consistently with higher mortality in older adults. However, total body mass includes fat and muscle, which have different metabolic effects. This study was designed to test the hypothesis that greater muscle mass in older adults is associated with lower all-cause mortality. METHODS: All-cause mortality was analyzed by the year 2004 in 3659 participants from the National Health and Nutrition Examination Survey III who were aged 55 years or more (65 years if women) at the time of the survey (1988-1994). Individuals who were underweight or died in the first 2 years of follow-up were excluded to remove frail elders from the sample. Skeletal muscle mass was measured using bioelectrical impedance, and muscle mass index was defined as muscle mass divided by height squared. Modified Poisson regression and proportional hazards regression were used to examine the relationship of muscle mass index with all-cause mortality risk and rate, respectively, adjusted for central obesity (waist hip ratio) and other significant covariates. RESULTS: In adjusted analyses, total mortality was significantly lower in the fourth quartile of muscle mass index compared with the first quartile: adjusted risk ratio 0.81 (95% confidence interval, 0.71-0.91) and adjusted hazard ratio 0.80 (95% confidence interval, 0.66-0.97). CONCLUSIONS: This study demonstrates the survival predication ability of relative muscle mass and highlights the need to look beyond total body mass in assessing the health of older adults. This study establishes the independent survival prediction ability of muscle mass as measured by bioelectrical impedance in older adults, using data from a large, nation- ally representative cohort. This is in sharp contrast to BMI, whose association with mortality in older adults is incon- sistent, at best. We conclude that measurement of muscle mass relative to body height should be added to the toolbox of clinicians caring for older adults. Future research should determine the type and duration of exercise interventions that improve muscle mass and potentially increase survival in well, older adults.

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

Scientific World Journal. 2014; 6: 672158

Ancianos fractura fémur Ancianos sanos Ancianos fractura fémur hombres mujeres n 78 94 25 75 Edad 73,9 (3,2) 74,9 (3,2) 82,8 * (7,2) 82,9 * (7,9) IMC (Kg/m2) 26,32 (3,0) 27,15 (4,2) 24,9 * (4,6) 25,7 * (3,1) MM (Kg) 27,13 (4,1) 16,93 (2,2) 23,5 (2,7) 14,7 (3,5) IMM (Kg/m2) 9,8 (1,3) 7,08 (0,8) 8,6 (1,2) 6,5 (1,1) Sarcopenia (%) 10 33 43 * 64 * En esta diapositiva pueden ver los resultados de prevalencia de sarcopenia en los 2 grupos de ancianos sanos y con fractura de femur Los ancianos con fractura de fémur tienen mayor prevalencia de sarcopenia La presencia de sarcopenia se relacionaba con la EDAD y con el IMC (con una p estadisticamente significativa p < 0.05)) * p < 0.05, respecto a sujetos del mismo sexo sanos

Age and Ageing 2010; 39: 412–423

Estudio Elli: Prevalencia de sarcopenia en pacientes de consulta y de residencias

Prevalencia en Residencias: Estudios comparativos

The SARC-F questionnaire has been developed as a possible rapid diagnostic test for sarcopenia.36 There are 5 SARC-F components: Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (Table 1). The scores range from 0 to 10, with 0 to 2 points for each component. Our preliminary studies have suggested that a score equal to or greater than 4 is predictive of sarcopenia and poor outcomes.

FNIH: >65 a (Found Nat Inst Health Sarcopenia Project) 10.63p (7113 H, 2950 M) Background. Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia. Methods. The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed. Results. The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%). Conclusions. The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment. Note: EWGSOP = European Working Group on Sarcopenia Older Persons; FNIH = Foundation of the National Institute of Health; IWG = International Working Group on Sarcopenia; NPA = negative percent agreement: the proportion of participants who were categorized as not having the condition by both the FNIH criteria and a second set of criteria divided by the number of participants who were categorized as not having the condition by the second set of criteria; PPA = positive percent agreement: the proportion of participants who were categorized as having the condition by both the FNIH criteria and a second set of criteria divided by the number of participants who were categorized as having the condition by the second set of criteria.

3260 p >65ª 83,4% sarcopenia según EWGSOP Ajustes cut-off: 34.2% (quintiles) 23.7% (Z-score) Background: there is a lack of consensus on the diagnosis of sarcopenia. A screening and diagnostic algorithm was proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). Objective: to assess the performance of the EWGSOP algorithm in determining the proportion of subjects suspected of having sarcopenia and selected to undergo subsequent muscle mass (MM) measurement. Design: a cross-sectional study. Setting: the cohorts, Frailty in Brazilian Older People Study—Rio de Janeiro (FIBRA-RJ), Brazil; Coyoacan Cohort (CC), Mexico City, Mexico; and Toledo Study for Healthy Aging (TSHA), Toledo, Spain. Subjects: three thousand two hundred and sixty community-dwelling individuals, 65 years and older. Methods: initially, the EWGSOP algorithm was applied using its originally proposed cut-off values for gait speed and handgrip strength; in the second step, values tailored for the specific cohorts were used. Results: using the originally suggested EWGSOP cut-off points, 83.4% of the total cohort (94.4% in TSHA, 75.5% in FIBRA-RJ, 67.8% in CC) would have been considered as suspected of sarcopenia. Adapted cut-off values lowered the proportion of abnormal results to 34.2% (quintile-based approach) and 23.71% (z-score approach). Conclusions: the algorithm proposed by the EWGSOP is of limited clinical utility in screening older adults for sarcopenia due to the high proportion of subjects selected to further undergo MM assessment. Tailoring cut-off values to specific characteristics of the population being studied reduces the number of people selected for MM assessment, probably improving the performance of the algorithm. Further research including the objective measure of MM is needed to determine the accuracy of these specific cut-off points.

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

Drugs Exercise Nutrition

[Intervention Review] Progressive resistance strength training for improving physical function in older adults Chiung-ju Liu, Nancy K Latham Revisión de 121 ensayos clínicos con 6.700 participantes que evalúa la utilidad de programas de ejercicio de resistencia (PER) sobre la función física: Estudios heterogéneos La mayoría de PER se realizan 3/semana, de intensidad elevada. Mejoría pequeña pero significativa en la habilidad física (33 trials) Mejoría en velocidad marcha (24t); levantarse de la silla (11t); fuerza muscular (73t) Efectos adversos escasos y leves: dolor articular y muscular Los PER son útiles para mejorar la fuerza muscular y la CF en gente mayor Cochrane Database of Systematic Reviews 2009, (3): CD002759

47 estudios: 1079 sujetos Presión EEII Presión tórax Tirón en polea Extensión rodilla

La ingestión de AAE incrementa la masa muscular y la síntesis proteica en personas mayores (N: 14 m; 3 meses; aleatorizado)

12 p (67a) suplementos de AAE/16 semanas:  2.4% MCM  14.2% FM en EEII  6.3% V. marcha  12.1% mejoría step test Marcha normal 5- step test Floor transfer test Flexo-extensión rodilla

La administración de Vitamina D (colecalciferol) disminuye el riesgo de caídas, relacionado probablemente con el aumento de la fuerza muscular. Los mecanismos incluyen el  de síntesis proteica por  RNAm a través de los receptores celulares para la Vit. D.

Efecto del ejercicio sobre la sarcopenia: Intervención nutricional: Revisión de 4810 artículos: 18 de prevalencia, 7 sobre ejercicio y 12 de nutrición. Prevalencia sarcopenia (15 comunidad, 2 residencial y 1 hospital de agudos): 1-29% en la comunidad; 14-33% en residencias y 10% en entorno hospitalaria. Efecto del ejercicio sobre la sarcopenia: Evidencia moderada que mejora la potencia y el rendimiento muscular. Intervención nutricional: Estudios heterogéneos con suplementos de AAE (leucina y HMB) demuestran una mejoría en la masa muscular y los parámetros de función física. Los suplementos con proteínas no han demostrado beneficios. Objective: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). Methods: PubMed and Dialog databases were searched ( January 2000–October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. Results: prevalence of sarcopenia was, with regional and age-related variations, 1–29% in community-dwelling populations, 14–33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including 2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. Conclusion: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

Definición de sarcopenia Fisiopatología Consecuencias de la sarcopenia Diagnóstico y prevalencia Tratamiento Conclusiones

Conclusiones La sarcopenia es un síndrome geriátrico que comporta tanto una pérdida de la función como de la masa muscular. La fisiopatología es compleja y multifactorial. La sarcopenia es uno de los ejes centrales en el desarrollo de fragilidad y confiere mal pronóstico en términos de salud (dependencia, morbilidad, mortalidad) El diagnóstico se basa en la demostración de una masa muscular disminuida y una alteración funcional muscular por diversas pruebas La prevalencia en nuestro medio es elevada

Conclusiones El ejercicio físico y mantener una nutrición adecuada (ingesta proteica adecuada, suplementos de AAE), son las únicas intervenciones que han demostrado eficacia para aumentar la masa y la potencia muscular en el anciano. Mantener los niveles de Vit. D correctos ha demostrado su eficacia en reducir las caídas y aumentar la fuerza muscular. Actualmente, ningún tratamiento farmacológico ha demostrado su eficacia en el tratamiento de la sarcopenia. Criterios diagnósticos bien establecidos ¿cuándo y a quiénes hemos de intervenir? ¿cuál es el tratamiento más adecuado? ¿qué indicadores?