|14TH WORLD CONGRESS OF THE ISPRM
|Year : 2021 | Volume
| Issue : 2 | Page : 100-103
Sarcopenia: Diagnosis, comorbidities, and management
Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Beihu Branch; Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital; Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan
|Date of Submission||12-Dec-2020|
|Date of Decision||23-Jan-2021|
|Date of Acceptance||11-Feb-2021|
|Date of Web Publication||08-Jun-2021|
Dr. Der-Sheng Han
Department of Physical Medicine and Rehabilitatison, National Taiwan University Hospital Bei-Hu Branch, No. 87, Nei-Jiang Rd., Wan-Hwa District, Taipei 108
Source of Support: None, Conflict of Interest: None
Sarcopenia, defined as loss of skeletal muscle mass and function, is attracting more and more public attention in the ageing world. It is associated with many co-morbidities, including frailty, cognitive impairment, depression, cardiovascular diseases, diabetes mellitus, and respiratory diseases, and incurs mortality at the end. Diagnostic consensuses are available, and the elderly at risk are encouraged to take suitable screening tests, such as muscle mass measurement, grip strength, and gait speed. Progressive resistance training is the mainstream to treat sarcopenia, yet, the multi-component exercise program is suggested for the frail elderly.
Keywords: Comorbidity, exercise, sarcopenia, skeletal muscle mass
|How to cite this article:|
Han DS. Sarcopenia: Diagnosis, comorbidities, and management. J Int Soc Phys Rehabil Med 2021;4:100-3
Owing to the aging population, every country is facing the burden of caring for the elderly. The geriatric syndrome has utilized a large proportion of medical care and long-term care. During the process of aging, the body composition changes, functional capacity reduces, muscle and bone mass decreases, and fat mass (FM) increases. The related diseases include sarcopenia, osteoporosis, and obesity. The reduction in muscle and bone mass is associated with a decline in physical activity volume and intensity, with an increased risk of chronic disease. Fortunately, physical activity significantly reduces this risk. This review will focus on the diagnosis, co-morbidities, and management of sarcopenia.
| Epidemiology|| |
The word “sarco” means flesh and “penia” indicates poverty. Therefore, sarcopenia refers to inadequate muscle mass. Sarcopenia is one of the most frequently discussed topics in the field of geriatric medicine. Using “sarcopenia” as the keyword to search from the PubMed, we found that the annual publications on sarcopenia increase exponentially. In 2019, the number of annual articles on sarcopenia was more than 1800. It is a novel and high-growth field.
Sarcopenia has many etiologies. The most common cause is senescence. Other factors include disuse, endocrine problems, starvation, insulin resistance, Vitamin D deficiency, and inflammation. We classified sarcopenia based on its causes. When it is caused by aging without other underlying causes, it is referred to as primary sarcopenia. If there are other causes, it is known as secondary sarcopenia. It might also be activity-related. For instance, those with reduced physical activity or in the zero-gravity condition will suffer from this type of secondary sarcopenia. Some cases related to specific diseases, such as congestive heart failure, liver cirrhosis, or chronic obstructive pulmonary diseases, can also induce sarcopenia. The other cause is nutrition related. Some elderly individuals who do not take sufficient protein in their diet, or have reduced intake of Vitamin D, will suffer from sarcopenia owing to the insufficiency of nutrition.
Referring to the consequences of sarcopenia, it is multi-dimensional. Sarcopenia impacts the state of health with high personal costs. It causes a higher risk for falls and fractures, impaired ability to perform activities of daily living, decreased basic metabolic rate, osteoporosis, impaired thermoregulation, mobility problems, decreased walking speed, malnutrition, and impaired balance. Finally, it induces frailty and increases mortality.
| Diagnosis|| |
A group of European geriatricians collectively discussed the diagnostic criteria for sarcopenia and published a high-impact article, which has been cited more than 7000 times. In this article, sarcopenia was defined as age-related loss of muscle mass and strength, both being critical points in diagnosis. The 2010 diagnostic criteria by the European Working Group on Sarcopenia in Older People (EWGSOP1) are composed of three main criteria of low muscle mass, muscle strength, and physical function. Low muscle mass can be measured using dual-energy X-ray absorptiometry (DXA), low muscle strength by grip strength, and low muscle function is measured by gait speed. Based on these three criteria, the severity of sarcopenia may be determined. A patient with low muscle mass only is considered presarcopenic. A patient with low muscle mass and either low strength or poor function are categorized as sarcopenic. A patient with all three criteria is diagnosed with severe sarcopenia. Classifying a specific cohort into four patient groups, namely normal, presarcopenia, sarcopenia, and severe sarcopenia, becomes convenient and easy with this consensus. The clinician can subsequently identify the risk factors and discuss the management of these different groups of patients.
Skeletal muscle (SM) mass can be measured with computed tomography (CT), magnetic resonance imaging (MRI), DXA, or bio-impedance analyzer (BIA). However, CT and MRI are very expensive and not frequently used. Therefore, DXA and BIA are suggested in this consensus. The BIA has no radiation and is easy to use. The movement of BIA machine for large-scale community screening is also feasible. The typical report contains a FM, lean mass, and appendicular muscle mass, and we can calculate the SM mass index using these parameters. In terms of muscle strength, the most convenient way is to measure the grip strength using a handheld dynamometer. The standard posture for grip strength measurement is holding the dynamometer with the elbow flexed at 90°, and the forearm in the neutral position. The patient squeezes the dynamometer thrice, and the maximum number is chosen as his/her grip strength. Grip strength is affected by race, sex, and body mass index (BMI). The age-trend of grip strength was similar to the functional status, with the peak value appeared in the 30s and reduced gradually. Regarding physical performance, we usually check the walking speed or usual gait speed, as the criteria. When measuring the gait speed, a 7 M line on the ground is drawn. For the first meter, the patient accelerated, between 1 M and 6 M, he simply walks at the usual speed, and in the last meter, he decelerated. The gait speed was calculated by dividing 5 by the time spent during the first to the sixth meter.
The cutoff point of low muscle mass is made in patients with muscle mass 2 standard deviations below the sex-matched young adult. The cutoff values of SM index (SMI) include 7.0 kg/m2 for the male and 5.5 kg/m2 for the female. In the 2010 consensus, a grip strength lower than 30 kg for men and 20 kg for women is deemed as low, and gait speed below 0.8 m/s is deemed as slow.
In 2014 in Taipei, Asian experts from Japan, Korea, China, Hong Kong, Taiwan, and Thailand together discussed the Asian consensus for sarcopenia. The algorithm was similar to the EWGSOP1, the 2010 version, and it suggested the race-specific cutoff values for the Asians.
After publication of these two consensus, the researchers can compare the prevalence of sarcopenia in different areas. The prevalence of disease is highly important since it is related to the allocation of resources. Before 2010, the prevalence of sarcopenia varied greatly, from 5% to 70% since every study used different diagnostic criteria. However, after 2010, the prevalence of sarcopenia became similar, with the lowest prevalence being 6% and the highest being 22%. In the National Taiwan University Hospital Beihu Branch, Han et al. collected 878 patients and measured the gait speed, grip strength, and muscle mass using the EWGSOP1 algorithm. The prevalence was approximately 6%, with males having a higher prevalence.
In 2019, the EWGSOP proposed a second version of the sarcopenia diagnostic criteria, EWGSOP2. The three components, that is low muscle mass, muscle strength, and physical function, are the same. However, the order changed, muscle strength is checked first. A person is deemed as “probable sarcopenia,” if he has low muscle strength. Second, muscle mass is measured. If muscle mass was reduced as well, the case is confirmed with “sarcopenia”. If all the three components are met, he/she is diagnosed with “severe sarcopenia”. The sarcopenic population diagnosed by EWGSOP2 has predominantly low muscle strength and is not the same as those diagnosed by EWGSOP1. SARC-F is suggested as a screening tool for sarcopenia in EWGSOP2. It is a self-reported questionnaire, with low-to-moderate sensitivity but very high specificity for predicting sarcopenia, mostly severe cases. It is an inexpensive and convenient method for sarcopenia screening. There are five questions in SARC-F: how much difficulty do you have in lifting and carrying 10 pounds; how much difficulty do you have walking across a room; how much difficulty do you have transferring from a chair or bed; how much difficulty do you have climbing a flight of 10 stairs; and how many times have you fallen in the past year? If the score is larger than four points, sarcopenia is suspected. EWGSOP2 is a new version of the diagnostic criteria. First, it employs SARC-F for detecting cases. Second, it measures muscle strength for identifying probable sarcopenia. In the clinical practice, a probable case is sufficient to trigger an assessment of causes and initiate intervention. Third, it measures muscle mass by DXA or BIA to confirm sarcopenia, and finally, it measures gait speed to determine the severity. The EWGSOP2 set new grip strength cutoff values: Lower than 27 kg as weakness in men and 16 kg in women. The cutoff values for appendicular SMI and walking speed are the same as EWGSOP1.
However, the two versions of the diagnostic criteria proposed by EWGSOP are not consistent. Yang et al. recruited 480 participants aged above 60 years from two community health centers in Urumqi, China and compared the consistency between EWGSOP1 and 2. They observed that the EWGSOP2 criteria did not agree with the EWGSOP1, AWGS, IWGA, and FNIH criteria defining sarcopenia. Besides, the risk factors associated with the EWGSOP2 defined that sarcopenia has no consistent patterns with the EWGSOP1, AWGS, IWGA, and FNIH criteria. The prevalence of sarcopenia by EWGSOP1 is 22% in men and 11% in women; however, the prevalence of sarcopenia by EWGSOP2 in the same cohort dropped to 6.5% in men and 3.3% in women. The positive percent agreement was quite low as 29%. The agreement index, kappa value, was only 0.39. A satisfactory agreement should be over 0.8. Thus, the validity of the EWGSOP2 consensus should be confirmed in further prospective studies.
| Muscle Mass Determination By Abdominal Computed Tomography|| |
Abdominal CT is a necessity in evaluating cancer patients in the Department of Internal Medicine. It provides details on specific muscles, adipose tissues (ATs), and organs better than DXA or BIA. This information is crucial for a precise anti-neoplastic prescription. Since the density of muscles was within a Hounsfield Unit (HU) range of −29 to +150, we can visualize muscle tissue using CT by setting an appropriate range of HU. In 2004, a research group at the Columbia University investigated the relationships between abdominal SM and AT areas from single images and total body component volumes in a large and diverse sample of healthy adult subjects. Total body SM and AT volumes were derived by whole-body multi-slice CT in 123 men (age 41.6 years; BMI: 25.9) and 205 women (age 47.8 years; BMI: 26.7). The muscle area at the third lumbar level (L3) had a high correlation with the whole-body lean mass. The muscles at the L3 region include the psoas, erector spinae, quadratus lumborum, transversus abdominis, external and internal obliques, and rectus abdominis. The determination coefficient (R-square) can reach 85.5%.
A subsequent study published in 2008 compared the body composition among BIA, DXA, and regional CT. It concluded that CT cut at the L3 level is a practical and precise approach to quantify body composition in patients with cancer. The regional analysis of FM and fat-free mass (FFM) at the L3 level with either DXA or CT strongly predicted whole-body FM and FFM (r = 0.86.0.94; P < 0.001). Therefore, we can translate the DXA cutoff value for sarcopenia into the CT L3 cutoff value. The cutoff value of sarcopenia for men is 55.4 cm2/m2 and for women is 38.9 cm2/m2.
By employing abdominal CT criteria, the body composition-related risk factors for cancer survival can be analyzed more easily. SM depletion is an independent prognostic factor for hepatocellular carcinoma. The predictive model is significant no matter the BMI is normal or decreased. In this study, the cutoff points at L3 SMI were 29.0 cm2/m2 in women and 36.0 cm2/m2 in men.
| Biomarker for Sarcopenia|| |
Medical clinicians usually want to perform a laboratory examination to diagnose disease, and sarcopenia is no exception. Myostatin is a negative regulator of SM growth. When this cytokine is upregulated, muscle atrophy will occur. Han et al. conducted a cross-sectional study recruiting a total of 100 cases receiving maintenance hemodialysis and assessed the patient's serum to detect the association between myostatin and grip strength. They reported that higher myostatin is associated with lower muscle function.
Follistatin is another cytokine related to the inflammation process. In a cross-sectional study recruiting 205 elderly individuals who underwent a health checkup, Liaw et al. observed that higher follistatin levels were independently associated with slower gait speed in community-dwelling elderly individuals. This suggests that serum follistatin level may be an indicator of mobility in elderly persons and may more particularly represent lower extremity function.
Kao et al. conducted gene expression studies on p16INK4a, a cell cycle-regulating gene. They reported that the p16INK4a expression increases with age in participants and is an aging marker. In this study, p16INK4a mRNA expression level was negatively associated with handgrip strength among community-dwelling older men.
In general, many candidate biomarkers are related to sarcopenia. However, the determining power is not sufficient to make a diagnosis or prognosis solely based on the laboratory data. Future studies combining all available biomarkers are needed to solve this problem.
| Comorbidity|| |
Sarcopenia is a geriatric syndrome that is associated with other common diseases in the elderly. The first one is frailty. Frailty is a state of age-related physiologic vulnerability resulting from impaired homeostatic reserve and a reduced capacity of the organism to withstand stress. Many common geriatric syndromes, including dementia, osteoporosis, depression, and malnutrition, have been proposed as contributors. There are five components of the diagnostic criteria for frailty. They are exhaustion, weight loss, low physical activity, slow walker, and low grip strength. The last two are the same as those for sarcopenia. Sarcopenia is also a phenotypic presentation of frailty. In the frailty vicious cycle, low muscle mass is followed by low strength, low VO2 max, decreased aerobic tolerance, slow walking speed, and then low physical activity. The prevalence of frailty in the geriatric population is approximately 10%, depending on age. The older population has higher frailty prevalence. Therefore, it is vital to identify the at-risk population early and provide early intervention.
Cognitive function impairment is another important comorbidity. In 2017, Chang et al. meta-analyzed the association between sarcopenia and dementia. A total of seven cross-sectional studies and approximately 6000 participants were included in this analysis, and they found that the adjusted-odds ratio (OR) in sarcopenic patients with dementia was approximately 2.246. A patient will have a doubled risk of developing dementia if they have sarcopenia.
A similar approach was used in the analysis of depression and sarcopenia. Chang et al. meta-analyzed 10 observational studies with 23000 participants and observed the crude OR to be 2.05.
A study group in the Australia and Netherlands used systematic review and meta-analysis to delineate the comorbidity of sarcopenia. They assessed 63 studies and about 40,000 individuals with a mean age of 65 years and concluded that the prevalence of sarcopenia is around 8%-16% in the general population; however, the prevalence will increase in the presence of comorbidities. Those patients with cardiovascular disease had a sarcopenia prevalence of 31%. In patients with dementia, the prevalence of sarcopenia will increase to 27%, 20% in patients with diabetes mellitus, and 25% in those with respiratory diseases.
Chang et al. also meta-analyzed the association between hepatic encephalopathy in liver cirrhosis and sarcopenia. Sarcopenia was positively associated with the presence of hepatic encephalopathy (OR 2.74).
| Exercise Intervention|| |
Exercise and nutrition are the mainstream treatments for sarcopenia. According to the American College of Sports Medicine guidelines for exercise testing and prescription, resistance exercise training is a major part of the treatment for sarcopenia. It can increase muscle strength, muscle quality, muscle endurance, and body composition. Free weight, elastic band, callisthenic, and weighing machines can all be employed to perform resistance training. In a randomized controlled trial conducted in Taiwan, Chang et al. reported the muscle strength increased double after structured resistance training and amino acid supplement for 12 weeks.
Not only resistance training but also aerobic exercise, flexibility, and even cognitive function training simultaneously will improve the functional status of the elderly population. This study was performed at the Taipei Veteran General Hospital and the National Yang-Ming University in Taiwan. About a total of 1000 elderly patients were treated using multidomain treatment that is 45 min of physical training, 6 min of cognitive training, and 50 min of educational health training once weekly for 12 months. The results revealed a significant progression in decreasing depression and enhancing muscle function. The effects can last up to 12 months. Cognitive function also improved after receiving the multidomain treatment.
| Conclusion|| |
Sarcopenia is characterized by low muscle mass, low muscle strength, and decreased functional performance in both EWGSOP1 and EWGSOP2 diagnostic criteria. However, inconsistency exists between EWGSOP1 and EWGSOP2. Most published literature used the first version, and the second version required further validation. SM mass determined by the cut at the third lumbar spine of abdominal CT is highly correlated with appendicular SMI. Physiatrists could cooperate with the internal medicine doctors to manage disease-related sarcopenia. Cutoff values for low muscle mass are available for different populations. Progressive resistance training is the mainstream exercise to increase muscle mass; however, multi-component exercise intervention is suggested for frail patients with sarcopenia as well.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rosenberg IH. Sarcopenia: Origins and clinical relevance. J Nutr 1997;127:990S-1.
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;39:412-23.
Han DS, Chang KV, Li CM, Lin YH, Kao TW, Tsai KS, et al
. Skeletal muscle mass adjusted by height correlated better with muscular functions than that adjusted by body weight in defining sarcopenia. Sci Rep 2016;6:1-8.
Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al
. Sarcopenia in Asia: Consensus report of the Asian working group for sarcopenia. J Am Med Dir Assoc 2014;15:95-101.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al.
Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing 2018;48:16-31.
Yang L, Yao X, Shen J, Sun G, Sun Q, Tian X, et al
. Comparison of revised EWGSOP criteria and four other diagnostic criteria of sarcopenia in Chinese community-dwelling elderly residents. Exp Gerontol 2020;130:110798. doi: 10.1016/j.exger.2019.110798.
Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab 2008;33:997-1006.
Chang KV, Chen JD, Wu WT, Huang KC, Hsu CT, Han DS. Association between loss of skeletal muscle mass and mortality and tumor recurrence in hepatocellular carcinoma: A systematic review and meta-analysis. Liver Cancer 2018;7:90-103.
Han DS, Chen YM, Lin SY, Chang HH, Huang TM, Chi YC, et al
. Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis. Clin Endocrinol (Oxf) 2011;75:857-63.
Liaw FY, Kao TW, Fang WH, Han DS, Chi YC, Yang WS. Increased follistatin associated with decreased gait speed among old adults. Eur J Clin Invest 2016;46:321-7.
Kao TW, Chen WL, Han DS, Huang YH, Chen CL, Yang WS. Examining how p16(INK4a) expression levels are linked to handgrip strength in the elderly. Sci Rep 2016;6:31905.
Chang KV, Hsu TH, Wu WT, Huang KC, Han DS. Association between sarcopenia and cognitive impairment: A systematic review and meta-analysis. J Am Med Dir Assoc 2016;17:1164.e7-15.
Chang KV, Hsu TH, Wu WT, Huang KC, Han DS. Is sarcopenia associated with depression? A systematic review and meta-analysis of observational studies. Age Ageing 2017;46:738-46.
Pacifico J, Geerlings MAJ, Reijnierse EM, Phassouliotis C, Lim WK, Maier AB. Prevalence of sarcopenia as a comorbid disease: A systematic review and meta-analysis. Exp Gerontol 2020;131:110801.
Chang KV, Chen JD, Wu WT, Huang KC, Lin HY, Han DS. Is sarcopenia associated with hepatic encephalopathy in liver cirrhosis? A systematic review and meta-analysis. J Formos Med Assoc 2018. doi: 10.1016/j.jfma.2018.09.011.
Chang KV, Wu WT, Huang KC, Han DS. Effectiveness of early versus delayed exercise and nutritional intervention on segmental body composition of sarcopenic elders - A randomized controlled trial. Clin Nutr 2020;S0261-5614(20)30354-X. doi: 10.1016/j.clnu.2020.06.037.
Chen LK, Hwang AC, Lee WJ, Peng LN, Lin MH, Neil DL, et al
. Efficacy of multidomain interventions to improve physical frailty, depression and cognition: Data from cluster-randomized controlled trials. J Cachexia Sarcopenia Muscle 2020;11:650-62.