Review
Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses

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Abstract

It is generally accepted that excessive loss of skeletal muscle mass is detrimental. Depletion of muscle mass is associated with poor prognosis in diabetes, trauma, sepsis, lung disease, renal failure and heart failure. In this review we discuss the emergence of muscle mass measurement using diagnostic imaging and the relationship between muscle mass and clinical outcome.

The pursuit of specific biochemical targets for reversal of muscle wasting, has spawned a host of investigator initiated research on muscle wasting as well as investigational new drug programs in pharmaceutical companies. Research on therapeutics targeting muscle is to a large extent done in animal models, with relatively few investigations done using human muscle or reporting upon muscle mass or muscle-related outcomes in humans. Since ∼1990, a quantitative approach, as opposed to a purely functional approach, to muscle atrophy and hypertrophy has become accessible with the advent of image-based assessments (dual energy X-ray absorptiometry, computed tomography and magnetic resonance imaging). These methods have high specificity and precision. In conclusion, current imaging techniques allow us to quantify the degree of muscularity of different individuals, to relate muscle mass to disease-specific outcomes, to define sarcopenia [severe muscle depletion] in quantitative terms, to detect the prevalence and rates of catabolic loss of muscle, the behavior of specific individual muscles and to define the efficacy of different therapies developed for the treatment of muscle wasting.

This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

Introduction

A wide body of evidence suggests that excessive loss of skeletal muscle is detrimental. Specific degenerative conditions of muscle, such as Duchenne muscular dystrophy, are fatal by 25 years of age. Muscle wasting is pervasive and not limited to rare disorders. Muscle wasting is an outcome of many chronic illnesses. Cancer, chronic obstructive pulmonary disease, heart failure and chronic renal failure, for example, are characterized by progressive involuntary weight loss and skeletal muscle loss. Muscle wasting is characteristic of such a broad range of physiological and pathological conditions that it has been considered to be part of a stereoptypical response to nutrient deprivation and systemic stress (Lecker et al., 2004). Indeed, different types of muscle atrophy appear to share a common transcriptional program that is activated in many systemic diseases (Lecker et al., 2004).

In this review we discuss the emergence of muscle mass measurement using diagnostic imaging and the relationship between muscle mass and clinical outcome.

Section snippets

Muscle mass measured from early times to the present

The diagnosis of muscle wasting has been documented since ancient times and this diagnosis was based on physiognomy for many centuries. Hippocrates remarked upon the facial features characteristic of temporal muscle wasting, “the nose sharp, the eyes sunken, the temples fallen in”. Tinsley reminded physicians of the value of these facial features in diagnosis and prognosis (Tinsley, 1918). Advanced old age, independent of the presence of any underlying disease is also associated with a

Muscle mass in human populations

There is variation in the absolute muscularity in any population of normal healthy individuals. Sex is a major determinant of muscularity, however there is a considerable degree of overlap between men and women (Baracos et al., 2010, Kelly et al., 2009, Martin et al., 2013, Shen et al., 2004). While the most muscular individuals are mostly male, the most muscular women are equally muscular as some men (Baracos et al., 2010, Kelly et al., 2009, Martin et al., 2013, Shen et al., 2004). Genetic

Clinical findings on skeletal muscle mass, atrophy and hypertrophy

High resolution CT images are normally found in the clinical record of a variety of patient groups (such as in oncology and hepatology), and some authors have advocated for the extraction of the body composition data from these records (MacDonald et al., 2011, Prado et al., 2009a). This approach makes maximal use of existing information and has permitted numerous retrospective and prospective studies. Thirty-three papers cited in this review report evaluations of muscle cross sectional area in

Conclusion

Sensitive and specific methods for the quantification of skeletal muscle in humans are providing new opportunities for translation of fundamental research in muscle biology from animal experimental systems to humans. Muscle wasting occurs in epidemic proportions in older individuals affected by chronic diseases and is prognostic of disease- and treatment specific morbidity and mortality. Individuals with severe muscle depletion are not merely unfit in the sense of their ability to perform work,

References (62)

  • J.R.L. Lieffers et al.

    A viscerally-driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole body energy demands

    American Journal of Clinical Nutrition

    (2009)
  • D.M. Mijnarends et al.

    Validity and reliability of tools to measure muscle mass, strength, and physical performance in community-dwelling older people: a systematic review

    Journal of the American Medical Directors Association

    (2013)
  • R.A. Murphy et al.

    Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung cancer patients

    Journal of Nutrition

    (2010)
  • P.D. Peng et al.

    Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis

    HPB: The Official Journal of the International Hepato Pancreato Biliary Association

    (2011)
  • C.M. Prado et al.

    Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study

    Lancet Oncology

    (2008)
  • G. Sergi et al.

    Body composition and resting energy expenditure in elderly male patients with chronic obstructive pulmonary disease

    Respiratory Medicine

    (2006)
  • W.J. Song et al.

    Association between obesity and asthma in the elderly population: potential roles of abdominal subcutaneous adiposity and sarcopenia

    Annals of Allergy, Asthma & Immunology

    (2012)
  • L. Thoresen et al.

    Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results

    Clinical Nutrition

    (2013)
  • S. Antoun et al.

    Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study

    Journal of Clinical Oncology

    (2010)
  • V. Baracos et al.

    Advances in the science and application of body composition measurement

    Journal of Parenteral and Enteral Nutrition

    (2012)
  • P.M. Cawthon et al.

    Health, aging and body composition study. Do muscle mass, muscle density, strength, and physical function similarly influence risk of hospitalization in older adults?

    Journal of the American Geriatrics Society

    (2009)
  • A.J. Cruz-Jentoft et al.

    Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people

    Age Ageing

    (2010)
  • D.P. Cuthbertson

    Observations on the disturbance of metabolism produced by injury to the limbs

    Quart Journal of Medicine

    (1932)
  • E. Del Fabbro et al.

    The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer

    Oncologist

    (2012)
  • K.M. Di Sebastiano et al.

    Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anaemia

    British Journal of Nutrition

    (2013)
  • W.R. Frontera et al.

    Muscle fiber size and function in elderly humans: a longitudinal study

    Journal of Applied Physiology

    (2008)
  • C. Glass et al.

    Sarcopenia and a physiologically low respiratory quotient in patients with cirrhosis: a prospective controlled study

    Journal of Applied Physiology

    (2013)
  • S.B. Heymsfield et al.

    Measurement of skeletal muscle: laboratory and epidemiological methods

    Journals of Gerontology Series A: Biological Sciences and Medical Sciences

    (1995)
  • T.L. Kelly et al.

    Dual energy X-ray absorptiometry body composition reference values from NHANES

    PLoS ONE

    (2009)
  • P. Kortebein et al.

    Effect of 10 days of bed rest on skeletal muscle in healthy older adults

    Journal of the American Medical Association

    (2007)
  • S.H. Lecker et al.

    Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression

    FASEB Journal

    (2004)
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    This article is part of a Directed Issue: Molecular basis of muscle wasting.

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