Chapter 2 Epidemiology of sarcopenia

The prevalence of sarcopenia depends on the definition applied and the attributes of the target population. EWGSOP, International Working group on Sarcopenia1 and Asian Working Group for Sarcopenia (AWGS2 released papers for the purpose of establishing international consensus and minimizing the differences between the various definitions of sarcopenia, and the prevalence of sarcopenia provided with the EWGSOP's definition (1–29%) was used.1 Reports from Japan were included among the reports reviewed, and the prevalence of sarcopenia was estimated to be between 11 and 24%. The prevalence of sarcopenia in Asia was also reported to be relatively high. However, as a result of a subsequent large-scale survey targeting Japanese, the prevalence of sarcopenia was found to be between 7.5% (n = 4811)3 and 8.2% (n = 1099).4 As such, whether sarcopenia can be particularly prevalent in Asia remains unclear.3, 4 Based on the results of a systematic review of recent studies regarding the prevalence of sarcopenia, the prevalence of this condition when defined as a decrease in skeletal muscle mass (skeletal muscle index [SMI]) was between 6.0% and 59.8%, and was between 7.5% and 77.6% when defined as a decrease in gait speed and grip strength, as in the EWGSOP definition. Both results clearly show the broad range of figures provided to describe the prevalence of sarcopenia.5 In addition, the prevalence of sarcopenia depends largely on the characteristics of the individuals. Among senior citizens residing in care facilities, the prevalence can range between 14 and 33%,1 and when this population also includes a large proportion of individuals with disabilities or those hospitalized to recover or undergo rehabilitative care, the prevalence rate is estimated to be 78%.6 Based on the above, specifying the prevalence of sarcopenia is difficult, because determining the presence of this condition depends on the definition applied and the individual attributes of the individuals. However, when reviewing the results of large-scale studies involving 1000 or more participants, the prevalence rate is estimated to be between 6% and 12%,3, 7, 8 which is generally considered to be the typical prevalence of sarcopenia. The causes of sarcopenia are divided into two broad classifications: primary sarcopenia, which are age-related changes leading to sarcopenia, and secondary sarcopenia, which consists of factors other than aging that can lead to sarcopenia, such as inadequate physical activity, other underlying diseases or malnutrition (Table 1).9 Age-related background factors for primary sarcopenia include decreased numbers of muscle satellite cells and motor neurons, decreased hormone secretion (human growth hormone, testosterone, ghrelin etc.), increased production of inflammatory cytokines, diminished mitochondrial function, abnormal myokine production, and weight loss accompanying decreased appetite, among various others. The deterioration of the body's capacity to synthesize muscle proteins and their increased degradation as a result of these factors are speculated to be related to the sarcopenia disease state.10, 11 With regard to secondary sarcopenia arising from inadequate exercise, many studies have found that skeletal muscle mass can decrease as a result of a lack of physical activity, whereas muscle hypertrophy can occur as a result of physical training. Increased quantities of nitrogen and potassium in skeletal muscle tissue, as well as decreased skeletal muscle mass, were observed after being bedridden for 6–7 weeks. Muscle strength in the lower extremities particularly decreased markedly by approximately 20%.12 Underlying conditions leading to secondary sarcopenia include organ failure, inflammatory diseases, malignant cancers and endocrine disorders, among others.9 In addition, because patients are forced to rest due to disease onset rather than the disease itself, this reduced activity can lead to the development of sarcopenia. Nutrition-related causes of secondary sarcopenia include deficient protein and branched-chain amino acid intake, as well as deficient intake of foods containing large quantities of anti-oxidants, such as n-3 long-chain polyunsaturated fatty acids, vitamins and carotenoids.10 The influence of aging on resting muscle protein synthesis and degradation is small13 and decreases in skeletal muscle mass occurring with age are thought to be the result of reductions in factors that stimulate protein synthesis as a result of inadequate exercise and malnutrition. Amino acid intake is effective for supporting muscle protein synthesis, but this effect is also dose-dependent, and in healthy adult men who do not exercise regularly, maintaining high concentrations of amino acids in the blood increases transport of amino acids to muscle cells; rapid stimulation of muscle protein synthesis and anabolic activity have been reported to result from increasing free amino acid concentration.14 This clinical question summarizes the relationships between prognoses and outcomes of patients with sarcopenia and major physical functions, falls and mortality. First, the presence of sarcopenia has been reported to result in a lower quality of life, frailty, higher risk of falls15, 16 and a higher risk of sustaining fractures after falling.17 An observational study found that sarcopenia increases the likelihood that patients will experience diminished physical functions, decreased gait speed or be hospitalized, as well as the overall risk of death.18 The relationship between the sarcopenia definition applied and patient prognosis was also studied. Although the risk of falls, impaired physical functions, hip fractures and all-cause mortality was higher regardless of the sarcopenia definition used, the potency of these risks varied substantially between definitions.19 Although a meta-analysis of 50 longitudinal studies found that muscle strength was correlated with impaired physical function, no significant relationship between skeletal muscle mass and physical function was observed.20 Based on the results of an observational study of an East Asian patient population, the risks of cardiovascular death and all-cause mortality were higher in patients with sarcopenia, particularly in those with sarcopenic obesity.21 Furthermore, an observational study carried out in South Korea found that patients with sarcopenic obesity were more likely to develop dyslipidemia than in non-obese patients with sarcopenia.22 Others have reported that sarcopenia is also an important prognostic factor with respect to severe cases of peripheral artery disease,23 and also that sarcopenia and cognitive decline are related.24 A survey of patients hospitalized at critical care hospitals showed that patients with sarcopenia have a higher risk of death.25 In addition, among older individuals undergoing emergency surgery, the risk of death was higher for those who had developed sarcopenia.26 Sarcopenia has been reported to be a predictor of complications or death in patients with liver cirrhosis and hepatocellular carcinoma, as well as those following hepatectomy.27-30 The presence of sarcopenic obesity has also been reported to increase the risk of infections after cardiac surgery.31 Sarcopenia is also a predictor of mortality risk after immunotherapy for diffuse large B-cell lymphoma32 as well as mortality risk after surgery for breast33 and colorectal cancers.34, 35 As a result of a meta-analysis of 38 studies investigating the prognostic predictive capability of sarcopenia with respect to the development of solid cancers, survival prognosis was observed to increase in line with increases in skeletal muscle mass.36 Other reports have pointed out that skeletal muscle mass and intramuscular fat mass of the psoas muscles are important predictors of survival prognosis after surgery for pancreatic cancer.37, 38 Follow-up surveillance of dialysis patients revealed that reduced muscle strength was associated with protein-energy wasting, decreased physical activity, inflammation and mortality risk, and this association was stronger than the association observed with skeletal muscle mass.39 This clinical question provides a summary of the prevalence of sarcopenia and sarcopenic obesity in patients with non-wasting non-communicable diseases, particularly diabetes. Based on a cross-sectional study of Indian patients, loss of skeletal muscle mass in patients with type 2 diabetes diagnosed using the EWGSOP definition and the SMI standard value by the dual-energy X-ray absorptiometry (DXA) method had a high odds ratio of 3.48 (95% confidence interval [CI] 1.61–7.50) compared with the control group.40 An article from the Netherlands also reported that reduction in skeletal muscle mass and muscle strength was observed in patients with type 2 diabetes, even after adjusting for age, BMI, fasting blood glucose, high-density lipoprotein cholesterol, branched-chain amino acids and protein intake.41 In the analysis of 14 528 participants during the Third National Health and Nutrition Examination Survey carried out in the USA, the prevalence of sarcopenia was determined to be less than two standard deviations from the young adult mean SMI value estimated based on BIA, and the relationship with diabetes was investigated. As a result, sarcopenia was concluded to be involved in glucose metabolism independently of obesity, and that this trend was stronger among patients younger than 60 years, and that decreases in skeletal muscle mass might be a predictor for diabetes.42 In Japan, the relationship between metabolic syndrome and sarcopenia diagnosed based on the EWGSOP criteria was studied among 1971 community-dwelling older people (mean age 72.9 years). Among patients with metabolic syndrome, the prevalence of sarcopenia was higher in men aged between 65 and 74 years, (odds ratio 4.99, 95% CI 1.73–14.40), and a particularly strong association was found between visceral fat mass and sarcopenia.43 The relationships between sarcopenia, sarcopenic obesity and metabolic syndrome have been investigated using data obtained from people living in Taiwan (mean age 63.6 years) who were diagnosed with sarcopenia based on SMI estimated from BIA or sarcopenic obesity based on BMI. Compared with healthy individuals, the odds ratio for development of metabolic syndrome among patients with sarcopenic obesity and non-obese patients with sarcopenia was 11.59 (95% CI 6.72–19.98) and 1.98 (95% CI 1.25–3.16), respectively.44 Although only reduced skeletal muscle mass (corresponding to the EWGSOP consensus definition of pre-sarcopenia) has been reported to be indicative of the prevalence of sarcopenia among patients with wasting diseases, few studies reported on the evaluation of sarcopenia based on the EWGSOP or the AWGS criteria. Based on a British study examining the prevalence of sarcopenia among 622 patients with stable chronic obstructive pulmonary disease (mean age 70.4 years), sarcopenia was found as a comorbidity in 14.5% of patients when applying the EWGSOP criteria, and no sex-based differences in prevalence were observed.45 Based on two reports, the prevalence of sarcopenia among HIV-infected patients was calculated (applying the EWGSOP criteria) to be 5.0% (n = 80, mean age 54 years)46 and 24.2% (n = 33, mean age 59 years).47 Almost no reports have been published to date regarding EWGSOP or AWGS-defined sarcopenia in patients with malignant cancer, and muscle mass is frequently assessed by cross-sectional computed tomography imaging at the L3 vertebra proximal to the psoas muscle. The prevalence of reduced skeletal muscle mass (pre-sarcopenia) as determined by this method of assessing muscle mass has been reported to be 26–65% among patients with gastric/esophageal cancer,48-51 19–39% among colorectal cancer patients,52-54 11–66% among hepatocellular carcinoma patients,27-29, 55-61 21–63% among patients with pancreatic cancer,62-65 29–68% among patients with renal cancer,66-68 60–68% among patients with urothelial cancer,69, 70 approximately 74% among patients with non-small cell lung cancer71 and approximately 55% among diffuse patients with large B-cell lymphoma.32, 72 The mean age of participants in these studies was approximately 65 years. In addition, based on a recent meta-analysis, solid cancer cases complicated by reduced skeletal muscle mass are associated with poor prognosis (hazard ratio 1.44, 95% CI 1.32–1.56).36 The prevalence of sarcopenia in patients with predialysis stage CKD (G3–G5) has been reported to be 5.9% (n = 287, mean age 59.9 years)73 and 14% (n = 148, mean age approximately 66 years).74 Based on a survey of South Korean patients with reduced skeletal muscle mass (pre-sarcopenia), 4.3% (n = 6437) were healthy or in CKD stage 1, 6.3% (n = 4747) were in stage 2 and 15.4% (n = 441) were between stages 3–5. The proportion of patients with decreased skeletal muscle mass was found to increase as CKD progresses to higher stages.75 Based on the results of a survey carried out in the USA, the risk of pre-sarcopenia is 2.58-fold higher in G4 patients compared with patients without CKD.76 Meanwhile, although the prevalence of sarcopenia in patients in the dialysis stage of CKD has been reported to be between 12.7% and 33.7%,39, 77-80 differences in the mean age (49.4–77.5 years) and in the method and criteria for evaluating skeletal muscle mass and muscle strength must be noted. Many reports have described the relationship between osteoporosis and sarcopenia. Because sarcopenia and osteoporosis have numerous shared causal factors, such as decreased age-related sex hormones, decreased anabolic hormones, vitamin D deficiency and decreased mechanical load, these conditions are believed to be closely related and can frequently appear as comorbidities.81 Osteoporosis can be complicated by sarcopenia,4, 82 leading to gait disorders and loss of balancing capacity.82 Among patients with a history of falls, the prevalence of sarcopenia is high in both men and women (odds ratio men: 4.42; women: 2.34).83 Complication by sarcopenia in osteoporosis causes falls due to the decrease in muscle mass and muscle strength, leading to further loss of bone mineral density and bone strength, resulting in osteoporotic fragility fractures.84 Conversely, the presence of osteoporosis significantly increases a patient's risk of developing sarcopenia in the near future.4 In the European Male Ageing Study, DXA was carried out, and grip strength and gait speed were measured in 679 male participants aged between 40 and 79 years residing in the UK and Belgium. Bone mineral density and the presence of sarcopenia were also determined based on the EWGSOP criteria. As a result, the presence of sarcopenia was found to be associated with reduced bone mineral density and osteoporosis.85 Yoshimura et al. examined the relationship between osteoporosis (World Health Organization criteria) and sarcopenia (AWGS criteria) based on the results of a survey of bone mineral density in 1099 participants residing locally, and determined that the prevalence of osteoporosis was 24.9%. In addition, although 18.9% of these patients were determined to be complicated by sarcopenia, the prevalence of sarcopenia was 8.2%, and the complication by osteoporosis was reported in 57.3% of these patients.4 As a result of a survey of 2400 participants investigating the rate of complication by sarcopenia by the degree of bone mineral density carried out by Miyakoshi et al., the prevalence of sarcopenia in the lumbar spine bone mineral density groups (normal, osteopenic and osteoporotic) was 10.4%, 16.8% and 20.4%, respectively. In addition, the prevalence of sarcopenia in the femoral proximal bone mineral density groups (normal, osteopenic and osteoporotic) was 9.0%, 17.8% and 29.7%, respectively.86 Among individuals aged >60 years with normal bone mineral density, the prevalence of sarcopenia has been reported to be between 8.3% and 70%.84 Yoshimura et al. analyzed whether osteoporosis (World Health Organization criteria) is correlated with future onset of sarcopenia (AWGS criteria) based on data gathered during a bone mineral density survey of 1099 community-dwelling older people. As a result, the cumulative incidence rate of sarcopenia was determined to be 2.0% annually, and the prevalence of osteoporosis was found to be significantly correlated with the development of sarcopenia (odds ratio 2.99 [adjusted for confounding factors]).4 Based on a survey of 591 patients hospitalized for hip fractures, sarcopenia was present in 340 of 531 (64.0%) and 57 of 60 (95%) in female and male patients, respectively; the prevalence of sarcopenia was particularly high in men compared with women (odds ratio 10.54).87 The prevalence rates of sarcopenia in the hip fracture and the vertebral fracture groups were 47.3% and 48.5%, respectively, and were higher than 31.8% of patients in the control group.88 Sarcopenia prevalence was also higher among patients residing in care facilities, and the rate of complication by osteoporosis was also high.89 The presence of sarcopenia is associated with a higher risk of bone fractures in older men.90 The presence of rheumatoid arthritis has been reported to be associated with disease duration and decreases in grip strength.91 Because neurodegenerative diseases affect activities of daily living, the prevalence of sarcopenia among such patients is estimated to be high. However, no studies on the prevalence of sarcopenia as defined based on the EWGSOP or AWGS criteria have been published to date, and the actual prevalence rate is unclear. Based on a National Center for Geriatrics and Gerontology study targeting 418 older individuals aged ≥60 years (mean age 77.3 years) receiving outpatient care for forgetfulness, sarcopenia as a comorbidity was reported in 8.6% (n = 35), 23.3% (n = 40) and 12.5% (n = 343) of older individuals with otherwise normal cognitive function, mild cognitive impairment and Alzheimer disease, respectively.92 However, although the presence of sarcopenia was determined based on the AWGS criteria, the Timed Up and Go test score was used as a measure of physical function as an alternative for normal gait speed. In a separate study, 1570 older individuals residing in 24 English districts (mean age 71.9 years)93 were placed into groups based on test your memory (TYM) scores (normal cognitive function group: TYM >47 [<80 years], TYM >46 [≥80 years]; mild cognitive impairment group: TYM 33–46 [<80 years], TYM 33–45 [≥80 years]; severe cognitive impairment group: TYM <33) obtained, after which the prevalence of severe sarcopenia (EWGSOP criteria) among individuals in each group was calculated. Based on the results, severe sarcopenia was identified in 1.5% (n = 801), 2.8% (n = 636) and 7.5% (n = 133) of individuals with normal cognitive function, mild cognitive impairment and severe cognitive impairment, respectively. Based on the results of a study carried out by the European Parkinson Therapy Center in Italy targeting 364 older individuals (aged ≥65 years; mean age 71.9 years) with parkinsonism (excluding drug-induced symptoms) and Mini-Mental State Examination scores ≥24, sarcopenia (EWGSOP criteria) was identified as a comorbidity in 6.6% of participants, and the prevalence rate of sarcopenia was 6.0% among the 235 participants presenting with Parkinson's disease, and this rate was 7.8% in patients with parkinsonism (excluding Parkinson's disease).94 Although the risk of complication by sarcopenia increases in malnourished patients, several reports have discussed the roles of proteins, amino acids and anti-oxidants in the pathogenesis of this condition.95-98, 37 The prevalence and severity of sarcopenia are higher in cases of cachexia, a type of severe malnutrition,99 and various other reports have stated that complication by sarcopenia occurs readily in patients with physical frailty.16, 35, 98-101 Spinal cord injury, inactivity and diminished capacity for physical activity are often associated with sarcopenia.102-104 Malnutrition is observed in 88–90% in patients with disuse syndrome. Furthermore, disuse syndrome frequently occurs in conjunction with deficient physical activity. Sarcopenia is believed to be strongly by these Meanwhile, exercise has been reported to influence muscle mass, muscle strength and physical functions, and exercise have been reported to as for sarcopenia. can increase muscle mass and muscle strength with or without protein individuals are to exercise for a Complication by sarcopenia occurs in patients with disuse syndrome as a result of decreases in the mechanical capacity of the Based on the results of a survey evaluating sarcopenia (EWGSOP criteria) in patients residing in Italy who were hospitalized at critical care facilities, the mortality rate after was determined to be higher in the sarcopenic group based on a survival The prevalence of sarcopenia among older individuals aged years who emergency surgery between and was and both the of complication and the mortality rate were higher among those with sarcopenia.26 As such, such as or surgery, can be to result in the development of secondary sarcopenia. for the In the Sarcopenia clinical regarding the relationship between the and the involved in sarcopenic diseases and sarcopenic diseases, each of the of in the years based on the following criteria. of and or more by a the of and the obtained from the or more of from or or more of the of the a as a of or more a of or more from daily by more than for clinical study or more or more by to a provided by a and on to the and other of or more such as or to the studies provided by of the are for the of clinical as or or of sarcopenic diseases and related diseases, to and and to the healthy of the target and to quality of the of of was in with the on of of Japan on of The are as is to not include and in a Japan Japan International Japan and for of for the systematic for of for the systematic for of for the systematic for of for the systematic for of for the systematic for of for the systematic for of for the systematic for of for the systematic The is not for the or of supporting by the than be to the for the