Chapter 1 Definitions and diagnosis of sarcopenia

Sarcopenia, which is derived from the Greek words sarx, meaning “muscle” and –penia, meaning “loss,” is a pathological concept first proposed by Rosenberg in 1989.1 Many early studies regarding sarcopenia focused only on skeletal muscle mass, but in recent years, greater importance has been placed on the decline in physical function decline due to the loss of skeletal muscle mass, and studies carried out have applied different definitions and diagnostic criteria for this condition. After the announcement of the European Working group on Sarcopenia in Older People (EWGSOP) on its operational definition in 20102 and the definition of the Asian Working group for Sarcopenia (AWGS) based on epidemiological data obtained from Japanese and other East Asian people,3 numerous other research groups also announced their own definitions for sarcopenia. In essence, each of the definitions proposed to date defines sarcopenia as a state of decreased skeletal muscle mass and the resulting physical dysfunction; skeletal muscle mass is a core element of all definitions. However, depending on the definition, muscle functions can be divided into those that require both muscle strength and physical functionality (e.g. gait speed) and/or only one of these elements (Table 1). However, grip strength and gait speed measurements required under each definition can be useful in the development towards adoption of unified definitions for muscle strength and physical function, respectively. The preclinical stage of sarcopenia presentation is referred to as pre-sarcopenia. The EWGSOP defines this state as one in which reduced skeletal muscle mass is not accompanied by diminished muscle strength or physical functionality.2 Dynapenia is defined as a state in which reduced muscle strength is not necessarily accompanied by decreased skeletal muscle mass.9 As such, measurement of skeletal muscle mass is not always necessary to diagnose dynapenia. Sarcopenic obesity is a state characterized by simultaneous presentation of sarcopenia and increased fat mass, and there is currently no established definition. Although obesity is defined based on BMI (square of bodyweight/height), in cases of sarcopenic obesity, increases in bodyweight due to greater fat mass accompany decreases in bodyweight due to loss of skeletal muscle mass, and as a result, BMI cannot be used to assess decreases in skeletal muscle mass and increases in body fat. Thus, to assess sarcopenic obesity, examining body composition is necessary, and in many cases dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis are used. However, the definition of sarcopenia in the context of sarcopenic obesity has not yet been defined, and furthermore, the definition of obesity differs greatly between Western and Asian ethnicities. As a result, proposed definitions for sarcopenic obesity vary. With respect to measurement methods, of 13 papers regarding sarcopenic obesity, seven studies used DXA,10-16 two studies used bioelectrical impedance analysis,17, 18 one study used computed tomography,19 one study used magnetic resonance imaging20 and two studies used calculation formulas21, 22 a majority of papers used the DXA technique. With respect to the diagnostic criteria for sarcopenia contained in these 13 papers, sarcopenia is defined as appendicular skeletal muscle mass of 1 standard deviation or less than the mean value for young individuals after correction using the square of the individual's height or bodyweight,10, 12, 14 or appendicular skeletal muscle mass of 2 standard deviations or less than the mean value for young individuals after correction using the square of the individual's height only,11, 13, 15, 18 or the total skeletal muscle mass percentage of ≤37% for men or 27.6% for women after correction using the individual's bodyweight,17 or defined using calculation formulae.21, 22 With regard to obesity, the condition is defined as a BMI of ≥25 kg/m2,10, 12, 17 a BMI of ≥30 kg/m2,19 a body fat percentage in the ≥60th percentile,11 the upper two quintiles for total body fat percentage of the study population,13 the highest quintile of the percentage body fat,18 a waist circumference of ≥90 cm for men or ≥85 cm for women,15 or based on methods using calculation formulae.21, 22 As such, the methods applied in the diagnosis of sarcopenia and obesity vary greatly by study. Sarcopenic obesity fulfills both the criteria for sarcopenia and obesity as described above. According to the criteria, four groups of individuals can be presented: a non-sarcopenic and non-obese (“non-S and non-O”) group, a non-sarcopenic and obese (“non-S and O”) group, a sarcopenic and non-obese (“S and non-O”) group and a sarcopenic and obese (“S and O”) group. Thereafter, characteristics of the four groups can be highlighted.10 Specifically, the S and O group had a higher prevalence of dyslipidemia compared with the S and non-O and non-S and O groups,10 whereas the prevalence (odds ratio) of hypertension was 1.5-fold greater in the S and non-O group, 2.08-fold higher in the non-S and O group, and 3.0-fold higher in the S and O group compared with the non-S and non-O group.12 In addition, the prevalence (odds ratio) of metabolic syndrome was 1.98-fold higher in the S and non-O group, 7.53-fold higher in the non-S and O group, and 11.59-fold higher in the S and O group compared with the non-S and non-O group.17 The S and O group had a larger number of women, and participants in this group also showed high fasting blood glucose and homeostatic model assessment for insulin resistance values.14 The participants in the S and O group showed lower bone density, balancing ability, parathyroid hormone levels and serum vitamin D concentrations,16 and the hazard ratio for mortality as a result of respiratory or gastrointestinal solid cancers was 4.2-fold higher than the non-S and O group.19 Declines in activities of daily living began to occur earlier in the participants in the S and O group compared with the non-S and O group.11 The S and O group participants developed depressive tendencies more frequently than the non-S and O group,18 and the S and O state has been described as the state most closely associated with impaired bodily function.21 References 2, 10 are prospective cohort studies, and the others are cross-sectional studies.11, 19 Although there are still a variety of different methods for assessing sarcopenia, seven diagnostic criteria (Table 2) have been confirmed.2-4, 6, 8, 23 The evaluation of people with sarcopenia is based on the diagnostic criteria proposed by EWGSOP in 2010;2 however, many subsequent reports have suggested their own cut-off values. In 2014, the AWGS announced a consensus on the diagnostic criteria for Asian people.3 In 2016, the Japan Society of Hepatology also proposed diagnostic criteria specialized for liver diseases.8 No consensus on diagnostic criteria for sarcopenic obesity has been confirmed to date. (DXA) Mean value for younger age cohort – value <2 SD (BIA) Mean value for younger age cohort – value <2 SD (DXA) Men <7.0 cm2/m2 Women <5.4 cm2/m2 (BIA) Men <7.0 cm2/m2 Women <5.7 cm2/m2 (DXA) Men <7.23 kg/m2 Women <5.67 kg/m2 (DXA) Men <0.789 kg/BMI Women <0.512 kg/BMI (DXA) Men <0.789 kg/BMI Women <0.512 kg/BMI (DXA) Mean value for younger age cohort (age 20–30 years) – value <2 SD (CT) Height-adjusted L3 level muscle mass Men <42 cm2/m2 Women <38 cm2/m2 (BIA) height-adjusted ASMI Men <7.0 cm2/m2 Women <5.7 cm2/m2 Men <30 kg Women <20 kg Men <26 kg Women <18 kg – – Men <26 kg Women <16 kg Men <26 kg Women <16 kg – – Men <26 kg Women <18 kg Of the seven confirmed diagnostic criteria of sarcopenia, six criteria recommended DXA as a diagnostic method, among which both the EWGSOP and AWGS criteria show bioelectrical impedance analysis cut-off values at the same time (Table 2). The procedure for correcting the value of “appendicular skeletal muscle mass” has not yet been unified, and in many cases appendicular skeletal muscle mass is corrected using the square of the individual's height. However, there are also other diagnostic criteria that call for correction using BMI or fat-free body mass in the extremities. “Muscle strength” is often evaluated based on grip strength, and cut-off values are provided for five of the seven confirmed diagnostic criteria (Table 2). In addition, “physical function” is generally evaluated based on the individual's gait speed, and five of seven criteria set established cut-off values for normal gait speed (the majority of which are >0.8 m/s or ≥1.0 m/s). In a recent study comparing different methods of diagnosing sarcopenia that examined 4000 people with sarcopenia in Hong Kong aged ≥65 years, the diagnosis based on the AWGS criteria was compared with those diagnosed based on other criteria with respect to physical impairment after 4 years and all-cause mortality after 10 years, and as a result, application of the AWGS criteria was determined to be valid in Asian people.24 Three methods of screening for sarcopenia have been confirmed to date,25-28 two of which are based on reports from Japan.26, 27 There have also been advancements in the development of alternative indicators using techniques and tools, such as biochemical testing,28-32 highly-sensitive C-reactive protein and immune complex C1q, C-terminal Agrin Fragment, telomere length, and the p53 codon 72 gene. Nevertheless, further study of factors, such as sex-related differences, remains necessary. See Figures S1–S3 for literature flowchart. In the Sarcopenia clinical practice guidelines 2017 edition preparation committee, regarding the economic relationship between the committee members and the companies involved in sarcopenic diseases and sarcopenic diseases, each member gave declarations of the conflict of interest status in the past 3 years based on the following criteria. Remuneration of officers and advisory positions (¥ one million or more annually paid by a single company/organization), the possession of shares and the profit obtained from the stock (¥ one million or more of annual profit from one company or 5% or more of the total shares of the company), a fee paid as a royalty fee (one patent royalty of ¥ one million or more per year), a lecture fee (the annual sum total of ¥500 000 or more from one company/organization), manuscript (manuscript fee, daily allowance paid by one company/organization totaling more than ¥500 000), research expenses (total amount paid for one clinical study ¥ one million yen or more per year), donation (¥ one million or more per year by one company/organization), affiliation to a donated fund laboratory provided by a company and so on (if affiliated to the department), and other remuneration (an annual total of ¥50 000 or more rewards, such as gifts or trip unrelated to the studies provided by company/organization). All members of the committee are responsible for the contents of “Sarcopenia clinical practice guidelines 2017” as medical or medical specialists or specialists of sarcopenic diseases and related diseases, to ensure scientific and medical fairness and appropriateness, to extend the healthy lifespan of the target patient, and to improve quality of life. Regarding the treatment of conflicts of interest, it was in accordance with the Committee on Conflicts of Interest of the Japan Medical Association “Guidelines on COI Management of Clinical Studies.” The company names declared are as follows (the applicable period is 1 January 2014 to 31 December 2016). It does not include publishers and organizations in a neutral position. Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AstraZeneca K.K., ALCARE Co., Ltd., Inter Reha Co., Ltd., Eisai Co., Ltd., MSD K.K., Otsuka Pharmaceutical Co., Ltd., ONO PHARMACEUTICAL CO., LTD., Kao Corporation, Kyowa Hakko Kirin CO., LTD., CLINICO CO., LTD., Kuredoru, Kowa Pharmaceutical Co.Ltd., SHIONOGI & CO., LTD., Sucampo Pharma, LLC, DAIICHI SANKYO COMPANY, LIMITED, Taisho Toyama Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., TSUKUI CORPORATION, TSUMURA & CO., TEIJIN PHARMA LIMITED., TOYOTA MOTOR CORPORATION, Eli Lilly Japan K.K., Boehringer Ingelheim, Nestle Japan Ltd., Novartis International AG, Bayer Yakuhin, Ltd., Pfizer Japan Inc., Bristol-Myers Squibb Company, HOYA CORPORATION and MOCHIDA PHARMACEUTICAL. Figure S1 Process flow for selection of literature sources for the Chapter 1-CQ1 systematic review. Figure S2 Process flow for selection of literature sources for the Chapter 1-CQ2 systematic review. Figure S3 Process flow for selection of literature sources for the Chapter 1-CQ3 systematic review. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.