Cover Page. The handle holds various files of this Leiden University dissertation

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1 Cover Page The handle holds various files of this Leiden University dissertation Author: Bijlsma, Astrid Title: The definition of sarcopenia Issue Date:

2 Chapter 1 General introduction and outline of thesis

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4 General introduction and outline of thesis 1 General introduction In developed countries, life expectancy is increasing and the elderly population is expanding rapidly. In the past 40 years the population of adults aged over 65 years has doubled to almost 2.6 million in 2011 in the Netherlands only (1). In this ageing society sarcopenia is an emerging problem. The term sarcopenia was coined in 1988 to describe the deficiency (penia) of flesh (sarx) as is often observed in old age. Annual loss of muscle mass has been reported as 1 to 2 percent from the age of 50 years onwards (2;3). While the loss of muscle mass seems to be accelerated in the presence of chronic disease, even in life-long trained athletes muscle mass is much lower in old as compared to young age (2). The introduction of the term sarcopenia contributed to research aimed to understand the consequences. There is a growing body of evidence that low muscle mass at old age is associated with self-reported physical disability and physical performance (4-6). The change of muscle mass is related to changes in muscle strength. However, to generate muscle strength other factors are important in addition to muscle mass, such as neural control, cognition, cardiovascular and joint function (7). Reduced muscle strength has been found to be associated with dependency in activities of daily living (8;9), cognitive decline (10-12), and mortality (13;14). Next to the generation of muscle strength, muscle tissue is an important reserve of body proteins and energy that can be used in extreme conditions of stress or malnutrition. Low muscle mass is associated with higher drug toxicity (15;16) and reduced insulin sensitivity (17). Because of the multiple functions of muscle tissue, biological aspects as well as functional and mechanical aspects can be considered as muscle related clinical outcome of interest when studying sarcopenia. Despite increasing knowledge about the consequences of sarcopenia, there is no consensus on the definition of sarcopenia. Since the coining of the term sarcopenia, researchers have been searching for diagnostic criteria for sarcopenia. This has lead to the use of a variety of diagnostic criteria for sarcopenia. In general, currently used diagnostic criteria for sarcopenia can be divided into criteria based on (1) low muscle mass (4;6), (2) low muscle strength (18), and (3) low walking speed (19;20). Muscle mass can be further divided into relative muscle mass and absolute muscle mass (figure 1) (21). With currently used diagnostic criteria for sarcopenia, the reported prevalence of sarcopenia varies extremely between elderly cohorts ranging from 7 to over 50% (22). It remains unknown whether this range can be explained by true differences between cohorts, or by the application of various diagnostic criteria to define sarcopenia in these cohorts. 11

5 Chapter 1 Fat Body mass Fat Fat Muscle Muscle Muscle A. B. C. Figure 1. Hypothetical example of the distribution of fat and muscle mass in three different persons with equal height, for visualization of differences between relative and absolute muscle mass. Person A and B have the same amount of body mass with a different amount of muscle mass and fat mass. Person B has a higher absolute (kg) amount of muscle mass and also a higher relative (percentage) amount of muscle mass compared to person A. Person C has the same absolute amount of muscle mass as person B, but with a higher body mass. Therefore person C has a lower relative muscle mass as compared to person B. Currenty, clinical awareness of the signs and consequences of sarcopenia is lacking. To diagnose sarcopenia in clinical practice a clear definition for sarcopenia is needed. The aim of this thesis is to assess the implications of the use of different diagnostic criteria for sarcopenia, and to define the most accurate criteria for sarcopenia. Outline of this thesis In chapter two the literature is reviewed for current knowledge on sarcopenia, concerning the diagnostic criteria for sarcopenia, the pathophysiology of sarcopenia, and its clinical implications. Chapter three compares the chronology in the history of defining osteoporosis with sarcopenia. This comparison is used to detect milestones needed to define both age-related disease definitions, and missing milestones still needed to reach consensus on the definition of sarcopenia. In chapter four the impact of the use of different diagnostic criteria on the prevalence of sarcopenia is assessed. This chapter answers the question whether differences in the reported prevalence of sarcopenia can be explained by the use of different diagnostic criteria within one study cohort. In the following four chapters diagnostic criteria for sarcopenia are compared in their association with different aspects of muscle related clinical outcome. The diagnostic criteria that are compared comprise relative muscle mass, absolute muscle mass, muscle strength, and walking speed. The muscle related 12

6 General introduction and outline of thesis 1 outcome of interest is: physical performance tested with the Timed get Up and Go test (TUG) and walking speed in chapter five; measures of insulin resistance derived from an oral glucose tolerance test in chapter six; whole body bone mineral density in chapter seven; and standing balance in chapter eight. In chapter nine the key findings of this thesis are summarized with a reflection, and recommendations for the definition of sarcopenia and future research are provided. 13

7 Chapter 1 Reference List (1) CBS statline, Statistics Netherlands (The Hague) (2) Buford TW, Anton SD, Judge AR, Marzetti E, Wohlgemuth SE, Carter CS, et al. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy. Ageing Res Rev 2010 Oct;9(4): (3) Marcell TJ. Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci 2003 Oct;58(10):M911-M916. (4) Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998 Apr 15;147(8): (5) Delmonico MJ, Harris TB, Lee JS, Visser M, Nevitt M, Kritchevsky SB, et al. Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women. J Am Geriatr Soc 2007 May;55(5): (6) Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 2002 May;50(5): (7) Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci 2008 Aug;63(8): (8) Rantanen T, Avlund K, Suominen H, Schroll M, Frandin K, Pertti E. Muscle strength as a predictor of onset of ADL dependence in people aged 75 years. Aging Clin Exp Res 2002 Jun;14(3 Suppl):10-5. (9) Taekema DG, Gussekloo J, Maier AB, Westendorp RG, de Craen AJ. Handgrip strength as a predictor of functional, psychological and social health. A prospective population-based study among the oldest old. Age Ageing 2010 May;39(3): (10) Alfaro-Acha A, Al SS, Raji MA, Kuo YF, Markides KS, Ottenbacher KJ. Handgrip strength and cognitive decline in older Mexican Americans. J Gerontol A Biol Sci Med Sci 2006 Aug;61(8): (11) Burns JM, Johnson DK, Watts A, Swerdlow RH, Brooks WM. Reduced lean mass in early Alzheimer disease and its association with brain atrophy. Arch Neurol 2010 Apr;67(4): (12) Taekema DG, Ling HY, Kurrle S, Cameron ID, Meskers CG, Blauw GJ, et al. Temporal relationship between handgrip strength and cognitive performance in oldest old people. Accepted in Age and Ageing (13) Ling CH, Taekema D, de Craen AJ, Gussekloo J, Westendorp RG, Maier AB. 14

8 General introduction and outline of thesis 1 Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study. CMAJ 2010 Mar 23;182(5): (14) Cooper R, Kuh D, Hardy R. Objectively measured physical capability levels and mortality: systematic review and meta-analysis. BMJ 2010;341:c4467. (15) Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage. Implications for drug therapy. Clin Pharmacokinet 1994 Apr;26(4): (16) Nawaratne S, Brien JE, Seeman E, Fabiny R, Zalcberg J, Cosolo W, et al. Relationships among liver and kidney volumes, lean body mass and drug clearance. Br J Clin Pharmacol 1998 Nov;46(5): (17) Kalyani RR, Metter EJ, Ramachandran R, Chia CW, Saudek CD, Ferrucci L. Glucose and Insulin Measurements From the Oral Glucose Tolerance Test and Relationship to Muscle Mass. J Gerontol A Biol Sci Med Sci 2011 Feb 24. (18) Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di IA, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol 2003 Nov;95(5): (19) Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010 Jul;39(4): (20) Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 2011 May;12(4): (21) Estrada M, Kleppinger A, Judge JO, Walsh SJ, Kuchel GA. Functional impact of relative versus absolute sarcopenia in healthy older women. J Am Geriatr Soc 2007 Nov;55(11): (22) Abellan van KG. Epidemiology and consequences of sarcopenia. J Nutr Health Aging 2009 Oct;13(8):

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