Minireviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Rheumatol. Feb 20, 2019; 9(1): 1-8
Published online Feb 20, 2019. doi: 10.5499/wjr.v9.i1.1
Association between sarcopenia and rheumatological diseases
Murat Korkmaz, Sibel Eyigor
Murat Korkmaz, Department of Physical Therapy and Rehabilitation, Faculty of Medicine, Afyon Saglik Bilimleri University, Afyonkarahisar 03000, Turkey
Sibel Eyigor, Department of Physical Therapy and Rehabilitation, Faculty of Medicine, Ege University, Izmir 35100, Turkey
ORCID number: Murat Korkmaz (0000-0002-3301-9950); Sibel Eyigor (0000-0002-9781-2712).
Author contributions: Korkmaz M performed the majority of the writing, designed the outline and coordinated the writing of the paper; Eyigor S performed data assessment and provided input for writing of the paper.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sibel Eyigor, MD, Professor, Department of Physical Therapy and Rehabilitation, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey. eyigor@hotmail.com
Telephone: +90-232-3903687 Fax: +90-232-3881953
Received: September 18, 2018
Peer-review started: September 18, 2018
First decision: November 5, 2018
Revised: November 12, 2018
Accepted: January 5, 2019
Article in press: January 5, 2019
Published online: February 20, 2019

Abstract

Sarcopenia (“sarx” for muscle, “penia” for loss) is an important problem in the elderly. Although muscle loss is a part of natural aging, excessive loss that limits physical activity is considered pathological. Sarcopenia is associated with age, malnutrition, physical inactivity, inflammatory stress and hormonal changes. Although relationships between sarcopenia and various chronic inflammatory diseases have been shown, the role of rheumatologic disease in sarcopenia development is currently unknown. Our aim in this mini-review was to increase the awareness of clinicians to sarcopenia, and to evaluate studies in which the relationship between sarcopenia and rheumatologic diseases was investigated. We also aimed to determine whether the available literature was sufficient to confirm a strong relationship between these conditions. Although our findings showed that diseases such as rheumatoid arthritis, osteoarthritis and systemic sclerosis may have a role in sarcopenia development and progress, the methodologies and results of the majority of studies were insufficient in determining direct causal relationships. We believe future studies would benefit from focusing on the factors and causes of sarcopenia, with a goal of determining the factors associated with rheumatologic disease that are most effective in sarcopenia development.

Key Words: Sarcopenia, Rheumatoid arthritis, Osteoarthritis, Rheumatologic diseases, Malnutrition, Chronic inflammatory diseases

Core tip: Although relationships between sarcopenia and various chronic inflammatory diseases have been shown, the role of rheumatologic disease in sarcopenia development is currently unknown. Our aim in this mini-review was to increase the awareness of clinicians to sarcopenia, and to evaluate studies in which the relationship between sarcopenia and rheumatologic diseases was investigated. As stated many times, the literature on this topic is quite limited; however, available data may be sufficient to associate sarcopenia with chronic inflammatory diseases.



INTRODUCTION

Sarcopenia is an important problem among elderly individuals. Approximately half of the population over the age of 80 is thought to have sarcopenia-related muscle loss[1]. This condition causes health problems, limits independence and increases morbidity and mortality due to an increased risk of falling[2,3]. Sarcopenia is thought to be highly associated with inflammatory stress, leading to muscle atrophy.

Rheumatologic diseases cause inflammation in various parts of the body, especially joints. As a result, these patients have severe joint pain, which limits their daily activity. Therefore, a significant association between sarcopenia and rheumatologic diseases could exist[4]. To date, only a handful of studies has explored the associations between rheumatologic disease and sarcopenia. Our aim was to evaluate the current literature on this topic and suggest future research directions.

SARCOPENIA

Sarcopenia was first described in 1988 by Rosenberg[5] as a reduction in bodily functions due to muscle mass depletion. The term is derived from two Greek words; "sarx" for muscle and "penia" for loss. In 2009, the International Working Group on Sarcopenia defined age-related sarcopenia as a loss of skeletal muscle mass and functions associated with aging. Later, the same group redefined the condition as "whole body or appendicular fat-free mass deficiency and combination of bad physical function"[6]. Due to this definition being insufficient in clinical practice, The European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as a syndrome characterized by progressive and generalized loss of skeletal mass, which can cause adverse consequences like physical disability, poor quality of life, and death[7].

Muscle mass is known to decrease linearly, beginning from the fourth decade of life. The rate of decrease is 8%-10% each decade until 70 years of age, and 15%-20% each decade thereafter[8-13]. Sarcopenia prevalence was found to be 14% among men aged < 70 years, 20% among men aged 70-74 years, 27% among men aged 75-80 years, and 53% among men aged > 80 years. This rate was 23%, 33%, 36% and 45% for the same age group of women, respectively[14]. However, previous research[15] stated that the prevalence of sarcopenia ranged from 5%-13% between the ages of 60-70, and between 11%-50% over the age of 80. These differences in the literature point to two important problems; firstly, the definition of sarcopenia can still be considered vague, and, secondly, clinicians may not be sufficiently aware of the condition.

In order to facilitate clinical practice, sarcopenia is divided into primary and secondary sarcopenia. Primary sarcopenia (also termed as age-related sarcopenia) develops due to ageing, while secondary sarcopenia is known to have various causes or triggers[16-19]. According to EWGSOP, sarcopenia is staged into three groups: presarcopenia, sarcopenia and severe sarcopenia. In presarcopenia, muscle mass is reduced, but muscle strength and physical performance are not affected. In sarcopenia, muscle mass as well as either muscle strength or performance is reduced. In severe sarcopenia, the reduction in muscle mass is accompanied by loss of both muscle strength and performance[7].

Although there are different recommendations for screening, elderly patients and/or patients with chronic illnesses like heart disease, patients whose history shows frequent falls, and those who are intentionally losing weight should be assessed for impairment in their daily activities[20]. EWGSOP has developed an algorithm for the detection of sarcopenic individuals in clinical and practical applications. According to their suggestions, the first step for sarcopenia diagnosis in individuals over 65 years of age is to evaluate their physical performance with simple walking and hand-shake tests. If further evaluation is required, the Short Physical Performance Battery (commonly known as SPPB), a composite of various tests that determine the balance, gait, strength and endurance of patients, is applied. The tests used in the implementation of the SPPB and their details are not within the scope of this review; however, details of the test and other specifics may be found in the 2010 study authored by Cruz-Jentoft et al[7]. After physical performance is evaluated, the determination of muscle mass can be performed via various modalities that give similar results, including computed tomography, magnetic resonance imaging and dual energy X-ray absorptiometry[21,22].

At this time, there is no FDA-approved agent for the treatment of sarcopenia[23]. Although testosterone, estrogen, and growth hormone replacement therapies have been evaluated, they may not be beneficial due to the possibility of severe side effects[24-26]. Other options include myostatin and myostatin receptor inhibitors, androgen receptor modulators, herbal supplements, and omega-3 fatty acid supplements[20]. During the last two decades, a number of treatment strategies for sarcopenia have been developed[27]. Almost all strategies involve an increase in exercise levels, especially aerobic and resistance exercises, which can increase muscle strength[7,28]. Nutritional support has also been shown to be crucial in those who have low-protein diets[29]. Several studies have also shown the benefits of balanced high-protein diets (up to 1.5 g/kg·d protein) and supplementation with both essential amino acids and vitamin D[30-33].

SARCOPENIA AND RHEUMATOLOGIC DISEASE
Sarcopenia and rheumatoid arthritis

Sarcopenia has been associated with numerous risk factors, the most prominent of these factors being old age and alterations in both hormonal and inflammatory parameters, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (commonly known as ESR)[34-36]. Rheumatoid arthritis (RA) is a disease that causes chronic inflammation and reduction in physical activity[37,38]. Skeletal muscle index has been shown to be lower in patients with RA compared to healthy controls[39]. Furthermore, a recent study revealed an association between sarcopenia and diseases that cause chronic inflammation. Therefore, a close relationship between RA and sarcopenia may exist.

In one study[39], RA patients with sarcopenia were found to have higher CRP values than those without, even though there was no difference between these patients in terms of DAS28 (disease activity score for RA). A similar systematic review comparing RA and sarcopenia etiology found that lower bone mineral density was more common among RA patients with sarcopenia[40]. These findings show that RA patients may be predisposed to sarcopenia regardless of RA severity. In addition, various studies have reported that the pain-related reduction in physical activity among RA patients can result in the development and progress of sarcopenia[38,41,42]. For instance, a study authored by Munro et al[43] found that CRP and ESR levels were negatively correlated with muscle mass in a cohort of 97 RA patients. Furthermore, muscle loss in RA, “rheumatoid cachexia” defined as loss of muscle mass in the absence of fat tissue reduction, has been shown to occur in many patients with RA[44]. The effects of cachexia overlap with sarcopenia pathophysiology, and most patients with cachexia are sarcopenic[45]. Considering that muscle loss is the hallmark of sarcopenia, rheumatoid cachexia could explain the higher frequency of sarcopenia among RA patients.

Furthermore, inflammatory parameters, including those that are altered in RA (tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), cytokines that tend to increase with age [interleukin 1 (IL-1) and interleukin-6 (IL-6)], have been associated with the development of sarcopenia[42,43]. However, the definition of sarcopenia was directly associated with muscle mass in both of these studies. Schaap et al[36] defined it as at least a 3% loss of muscle mass, while Ngeuleu et al[37] defined it as a reduction in relative skeletal mass index (< 5.5 kg/m2 for women and < 7.26 kg/m2 for men). In addition to population-based studies, it is known that cytokines, especially TNF-α and IL-6, stimulate protein catabolism in the muscle, leading to muscle loss. Thus, diseases with chronic inflammatory characteristics are thought to cause secondary sarcopenia, which exemplifies another association between RA and sarcopenia[46,47].

Although many of the aforementioned studies have reported significant associations between RA and sarcopenia in terms of etiology and laboratory/clinical findings, there are also studies that did not find any relationship[48]. The majority of studies that suggest a very close association between the two diseases have only revealed associations between specific etiological factors and some clinical findings. Therefore, although it is tempting to conclude that RA and sarcopenia have a causal relationship (one way or the other), the literature is actually insufficient to draw such a conclusion. Further controlled studies, with the goal of determining which condition causes or leads to the other (preferably prospective studies or comparison of patients with early/long term disease), are required to confirm whether a causal relationship exists between the two diseases.

Sarcopenia and osteoarthritis

Osteoarthritis (OA) is associated with aging, chronic inflammation and obesity. Considering that aging and chronic inflammation are also factors for sarcopenia development and progress, a significant association between these two conditions may exist. Various studies have shown an association between the type of cytokines that increase during both conditions[49,50], while one study reported that OA and sarcopenia may potentiate each other’s inflammatory activities through the production of pro-inflammatory agents[51]. Another important point is the fact that patients with OA have lowered physical activity, which may lead to muscle loss and sarcopenia[52,53].

A study by Kemmler et al[54] found that sarcopenia was more common in women with OA than those without. However, interestingly, muscle mass results were similar in both OA patients and those without arthritis. On the other hand, Toda et al[55] reported that reduced lower limb mass was frequent in patients with OA. This may suggest that the joints affected by OA are an important factor for the development of sarcopenia. Lower physical activity, especially in those with painful knee and hip joints, may translate to the exacerbation of muscle loss throughout the body, and could show a causal relationship between OA and sarcopenia[56]. This conclusion is supported by reports of lower skeletal muscle mass in patients with knee and hip OA[57,58]. However, it is important to keep in mind that the inflammatory condition brought about by sarcopenia could also both increase inflammatory burden in joints and increase OA severity. Current data are not sufficient to determine which condition causes or accelerates the other.

Therefore, it is apparent that current research has been unfruitful in determining whether sarcopenia is the cause or result of muscle problems in inflammatory diseases. Nevertheless, it is safe to say that a relationship between inflammatory stress and sarcopenia exists; however, further studies are required to determine the weight and direction of this relationship. Future studies that evaluate whether sarcopenia frequency is affected in those with inflammatory disease without joint pain (or the opposite) could potentially elucidate the nature of these associations.

Sarcopenia and spondyloarthropathies

Ankylosing spondylitis (AS) is a chronic inflammatory condition known to cause bone loss; however, muscle loss is not widely reported[59-61]. To our knowledge, only two studies suggest that muscle mass is reduced in those with AS. The first study[62] reported that patients with AS had significant reduction in lean body mass, while the second study evaluated muscle mass directly, and showed that both muscle mass and functional capacity were significantly reduced in patients with AS. The remaining studies showed no associations between AS and muscle mass[60,63]. While differences in measurement techniques and study design may cause variations in results, it is also crucial to keep in mind that AS primarily affects the vertebrae. Meanwhile, other joints are affected to a lesser degree, if at all. Thus, limitations in the movement of vertebrae may not be enough to accelerate or cause sarcopenia, even with increased inflammation.

One report[59] claims that patients with spondyloarthropathy had significantly lower muscle mass compared to controls. However, their findings showed a lack of association between changes in muscle mass and disease duration. This is an unexpected result, because if there was a strong relationship between the diseases, the findings of sarcopenia (muscle loss) should have worsened proportionately with disease duration. Therefore, we can conclude that the very limited literature on this topic does not confirm a positive relationship between spondyloarthropathy and sarcopenia.

Sarcopenia and other rheumatologic diseases

In a study comparing sarcopenia frequency among patients with chronic inflammatory diseases and non-inflammatory controls, patients with systemic lupus erythematosus were found to have significantly higher sarcopenia frequency than controls[4]. However, the definition of sarcopenia was accepted as unintentional loss of > 10 pounds of weight in the previous year, while weakness was defined separately. This definition is lacking in terms of determining whether the patient truly had sarcopenia; however, considering that systemic lupus erythematosus patients may require high doses of corticosteroid therapy, the loss of muscle mass is to be expected. Future studies would benefit from correctly defining and evaluating sarcopenia with regard to steroid dose.

Muscle involvement is a very common finding in patients with systemic sclerosis (SSc), which may contribute to the development of sarcopenia. Although the literature is methodologically limited, many studies report that SSc patients have increased muscle loss, and sarcopenia is diagnosed in up to 20%–54% of these patients[64,65]. In a relatively larger study comprised of 61 SSc patients, it was reported that lean mass was significantly reduced in women with SSc. Furthermore, the same study showed that longer duration with SSc was associated with higher risk for sarcopenia[66]. The latter finding was also confirmed by Wang et al[67].

Psoriatic arthritis is another disease with chronic activation of inflammation, which primarily affects the skin in the form of lesions of varying severity. Fatigue is a common but underestimated feature of psoriasis; however, there was no association between psoriasis severity and fatigue severity, which may suggest that other factors lead to fatigue, such as sarcopenia development due to chronic inflammation[68]. A study by Krajewska-Włodarczyk et al[69] suggested that the quality of life of psoriasis patients was affected by fatigue, an underestimated and often overlooked clinical finding in psoriasis. Although the study did not directly evaluate sarcopenia, future studies may benefit from the evaluation of sarcopenia among patients with psoriatic arthritis, especially considering the association between inflammation and fatigue.

Although the majority of studies have not associated gout with sarcopenia, one large cross-sectional study found that the risk of sarcopenia was higher among gout patients[70]. In contrast, several studies have suggested that therapy for gout (allopurinol) could be protective against sarcopenia[71]. Allopurinol inhibits the enzyme xanthine oxidase, and has been shown to prevent the production of free radicals during muscle contraction[71]. Further studies are required to determine whether allopurinol can be used as a treatment in patients with sarcopenia.

Studies in this field have mostly focused on muscle mass in sarcopenic individuals. Although this approach is not entirely erroneous, it is important to remember that muscle mass evaluations may not capture the whole clinical picture in patients with sarcopenia, as these patients mainly suffer from reduced physical performance and muscle strength. Therefore, correctly defining sarcopenia in future studies will be of utmost importance in order to obtain accurate results. Furthermore, it is quite apparent that increased inflammation contributes to sarcopenia development. Therefore, sarcopenia research may benefit from better study designs that aim to discriminate between muscle strength and mass, while also taking into account the effect of inflammation on the condition. However, the available literature indicates significant associations between these inflammatory diseases and sarcopenia, a disease that causes significant morbidity and mortality. This finding, even by itself, can be considered as an important step in a field that has received insufficient attention.

CONCLUSION

As stated many times, the literature on this topic is quite limited; however, available data may be sufficient to associate sarcopenia with diseases such as RA, OA and SSc. Nevertheless, the analyses in the majority of these studies are not sufficient to support the existence of a causal relationship between the diseases. Additionally, we have observed that sarcopenia definitions in these studies did not conform to EWGSOP recommendations; therefore, the approach to sarcopenia diagnosis (and its definition) in these studies may have caused the differences observed in the results. Future studies should primarily focus on illuminating causal relationships between sarcopenia (with a correct definition) and rheumatologic diseases, and determining whether the presence of inflammation or the physical limitations brought by rheumatologic diseases are more critical in the development of sarcopenia.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Rheumatology

Country of origin: Turkey

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): D

Grade E (Poor): 0

P- Reviewer: Barone M, Bourgoin SG, Cavallasca JA S- Editor: Cui LJ L- Editor: Filipodia E- Editor: Zhang YL

References
1.  Santilli V, Bernetti A, Mangone M, Paoloni M. Clinical definition of sarcopenia. Clin Cases Miner Bone Metab. 2014;11:177-180.  [PubMed]  [DOI]
2.  Cawthon PM, Marshall LM, Michael Y, Dam TT, Ensrud KE, Barrett-Connor E, Orwoll ES; Osteoporotic Fractures in Men Research Group. Frailty in older men: prevalence, progression, and relationship with mortality. J Am Geriatr Soc. 2007;55:1216-1223.  [PubMed]  [DOI]
3.  Hartman MJ, Fields DA, Byrne NM, Hunter GR. Resistance training improves metabolic economy during functional tasks in older adults. J Strength Cond Res. 2007;21:91-95.  [PubMed]  [DOI]
4.  Santos MJ, Vinagre F, Canas da Silva J, Gil V, Fonseca JE. Body composition phenotypes in systemic lupus erythematosus and rheumatoid arthritis: a comparative study of Caucasian female patients. Clin Exp Rheumatol. 2011;29:470-476.  [PubMed]  [DOI]
5.  Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127:990S-991S.  [PubMed]  [DOI]
6.  Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, Abellan van Kan G, Andrieu S, Bauer J, Breuille D, Cederholm T, Chandler J, De Meynard C, Donini L, Harris T, Kannt A, Keime Guibert F, Onder G, Papanicolaou D, Rolland Y, Rooks D, Sieber C, Souhami E, Verlaan S, Zamboni M. 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;12:249-256.  [PubMed]  [DOI]
7.  Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39:412-423.  [PubMed]  [DOI]
8.  Metter EJ, Conwit R, Tobin J, Fozard JL. Age-associated loss of power and strength in the upper extremities in women and men. J Gerontol A Biol Sci Med Sci. 1997;52:B267-B276.  [PubMed]  [DOI]
9.  Grimby G, Saltin B. The ageing muscle. Clin Physiol. 1983;3:209-218.  [PubMed]  [DOI]
10.  Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, Simonsick EM, Tylavsky FA, Visser M, Newman AB. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61:1059-1064.  [PubMed]  [DOI]
11.  Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, Fiatarone Singh MA. Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol A Biol Sci Med Sci. 2001;56:B209-B217.  [PubMed]  [DOI]
12.  Iannuzzi-Sucich M, Prestwood KM, Kenny AM. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci. 2002;57:M772-M777.  [PubMed]  [DOI]
13.  Newman AB, Lee JS, Visser M, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Nevitt M, Harris TB. Weight change and the conservation of lean mass in old age: the Health, Aging and Body Composition Study. Am J Clin Nutr. 2005;82:872-8; quiz 915-6.  [PubMed]  [DOI]
14.  Baumgartner RN, Stauber PM, McHugh D, Koehler KM, Garry PJ. Cross-sectional age differences in body composition in persons 60+ years of age. J Gerontol A Biol Sci Med Sci. 1995;50:M307-M316.  [PubMed]  [DOI]
15.  Johnson MA, Dwyer JT, Jensen GL, Miller JW, Speakman JR, Starke-Reed P, Volpi E. Challenges and new opportunities for clinical nutrition interventions in the aged. J Nutr. 2011;141:535-541.  [PubMed]  [DOI]
16.  Shinohara M. Adaptations in motor unit behavior in elderly adults. Curr Aging Sci. 2011;4:200-208.  [PubMed]  [DOI]
17.  Walston JD. Sarcopenia in older adults. Curr Opin Rheumatol. 2012;24:623-627.  [PubMed]  [DOI]
18.  Marsh AP, Rejeski WJ, Espeland MA, Miller ME, Church TS, Fielding RA, Gill TM, Guralnik JM, Newman AB, Pahor M; LIFE Study Investigators. Muscle strength and BMI as predictors of major mobility disability in the Lifestyle Interventions and Independence for Elders pilot (LIFE-P). J Gerontol A Biol Sci Med Sci. 2011;66:1376-1383.  [PubMed]  [DOI]
19.  Cruz-Jentoft AJ, Landi F, Topinková E, Michel JP. Understanding sarcopenia as a geriatric syndrome. Curr Opin Clin Nutr Metab Care. 2010;13:1-7.  [PubMed]  [DOI]
20.  Gupta S, Dhillon RJS, Hasni S. Sarcopenia: A Rheumatic Disease? Rheum Dis Clin North Am. 2018;44:393-404.  [PubMed]  [DOI]
21.  Working Group on Functional Outcome Measures for Clinical Trials. Functional outcomes for clinical trials in frail older persons: time to be moving. J Gerontol A Biol Sci Med Sci. 2008;63:160-164.  [PubMed]  [DOI]
22.  Chien MY, Huang TY, Wu YT. Prevalence of sarcopenia estimated using a bioelectrical impedance analysis prediction equation in community-dwelling elderly people in Taiwan. J Am Geriatr Soc. 2008;56:1710-1715.  [PubMed]  [DOI]
23.  Dhillon RJ, Hasni S. Pathogenesis and Management of Sarcopenia. Clin Geriatr Med. 2017;33:17-26.  [PubMed]  [DOI]
24.  Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc. 2003;51:101-15; discussion 115.  [PubMed]  [DOI]
25.  Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003;289:3243-3253.  [PubMed]  [DOI]
26.  Cruz-Jentoft AJ. Sarcopenia: what should a pharmacist know? Farm Hosp. 2017;41:543-549.  [PubMed]  [DOI]
27.  Wakabayashi H, Sakuma K. Comprehensive approach to sarcopenia treatment. Curr Clin Pharmacol. 2014;9:171-180.  [PubMed]  [DOI]
28.  Périer RC, Praz V, Junier T, Bonnard C, Bucher P. The eukaryotic promoter database (EPD). Nucleic Acids Res. 2000;28:302-303.  [PubMed]  [DOI]
29.  Sökmen ÜN, Dişçigil G. Yaşlılıkta sarkopeni. he Journal of Turkish Family Physician. 2017;08:49-54.  [PubMed]  [DOI]
30.  Kuyumcu ME. Sarkopenik Yaşlı Hastalarda Ultrasonografik Olarak Kas Mimarisinin Değerlendirilmesi. 2014;.  [PubMed]  [DOI]
31.  Paddon-Jones D, Sheffield-Moore M, Katsanos CS, Zhang XJ, Wolfe RR. Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein. Exp Gerontol. 2006;41:215-219.  [PubMed]  [DOI]
32.  Rondanelli M, Klersy C, Terracol G, Talluri J, Maugeri R, Guido D, Faliva MA, Solerte BS, Fioravanti M, Lukaski H, Perna S. Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. Am J Clin Nutr. 2016;103:830-840.  [PubMed]  [DOI]
33.  Dawson-Hughes B. Serum 25-hydroxyvitamin D and functional outcomes in the elderly. Am J Clin Nutr. 2008;88:537S-540S.  [PubMed]  [DOI]
34.  Bano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B, Manzato E, Sergi G, Veronese N. Inflammation and sarcopenia: A systematic review and meta-analysis. Maturitas. 2017;96:10-15.  [PubMed]  [DOI]
35.  Cesari M, Kritchevsky SB, Newman AB, Simonsick EM, Harris TB, Penninx BW, Brach JS, Tylavsky FA, Satterfield S, Bauer DC, Rubin SM, Visser M, Pahor M; Health, Aging and Body Composition Study. Added value of physical performance measures in predicting adverse health-related events: results from the Health, Aging And Body Composition Study. J Am Geriatr Soc. 2009;57:251-259.  [PubMed]  [DOI]
36.  Schaap LA, Pluijm SM, Deeg DJ, Visser M. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006;119:526.e9-526.17.  [PubMed]  [DOI]
37.  Ngeuleu A, Allali F, Medrare L, Madhi A, Rkain H, Hajjaj-Hassouni N. Sarcopenia in rheumatoid arthritis: prevalence, influence of disease activity and associated factors. Rheumatol Int. 2017;37:1015-1020.  [PubMed]  [DOI]
38.  Rall LC, Roubenoff R. Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions. Rheumatology (Oxford). 2004;43:1219-1223.  [PubMed]  [DOI]
39.  Doğan SC, Hizmetli S, Hayta E, Kaptanoğlu E, Erselcan T, Güler E. Sarcopenia in women with rheumatoid arthritis. Eur J Rheumatol. 2015;2:57-61.  [PubMed]  [DOI]
40.  Masuko K. Rheumatoid cachexia revisited: a metabolic co-morbidity in rheumatoid arthritis. Front Nutr. 2014;1:20.  [PubMed]  [DOI]
41.  Torii M, Hashimoto M, Hanai A, Fujii T, Furu M, Ito H, Uozumi R, Hamaguchi M, Terao C, Yamamoto W, Uda M, Nin K, Morita S, Arai H, Mimori T. Prevalence and factors associated with sarcopenia in patients with rheumatoid arthritis. Mod Rheumatol. 2018;1-7.  [PubMed]  [DOI]
42.  Roubenoff R, Roubenoff RA, Cannon JG, Kehayias JJ, Zhuang H, Dawson-Hughes B, Dinarello CA, Rosenberg IH. Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J Clin Invest. 1994;93:2379-2386.  [PubMed]  [DOI]
43.  Munro R, Capell H. Prevalence of low body mass in rheumatoid arthritis: association with the acute phase response. Ann Rheum Dis. 1997;56:326-329.  [PubMed]  [DOI]
44.  Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L, Palla SL, Ambrosius WT, Tracy RP, Pahor M. Sarcopenia, obesity, and inflammation--results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study. Am J Clin Nutr. 2005;82:428-434.  [PubMed]  [DOI]
45.  Westhovens R, Nijs J, Taelman V, Dequeker J. Body composition in rheumatoid arthritis. Br J Rheumatol. 1997;36:444-448.  [PubMed]  [DOI]
46.  Greenlund LJ, Nair KS. Sarcopenia--consequences, mechanisms, and potential therapies. Mech Ageing Dev. 2003;124:287-299.  [PubMed]  [DOI]
47.  Girasole G, Giuliani N, Modena AB, Passeri G, Pedrazzoni M. Oestrogens prevent the increase of human serum soluble interleukin-6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro. Clin Endocrinol (Oxf). 1999;51:801-807.  [PubMed]  [DOI]
48.  Metsios GS, Stavropoulos-Kalinoglou A, Douglas KM, Koutedakis Y, Nevill AM, Panoulas VF, Kita M, Kitas GD. Blockade of tumour necrosis factor-alpha in rheumatoid arthritis: effects on components of rheumatoid cachexia. Rheumatology (Oxford). 2007;46:1824-1827.  [PubMed]  [DOI]
49.  Haseeb A, Haqqi TM. Immunopathogenesis of osteoarthritis. Clin Immunol. 2013;146:185-196.  [PubMed]  [DOI]
50.  Loeser RF. Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med. 2010;26:371-386.  [PubMed]  [DOI]
51.  Papalia R, Zampogna B, Torre G, Lanotte A, Vasta S, Albo E, Tecame A, Denaro V. Sarcopenia and its relationship with osteoarthritis: risk factor or direct consequence? Musculoskelet Surg. 2014;98:9-14.  [PubMed]  [DOI]
52.  Zancheta R, Possi AP, Planeta CS, Marin MT. Repeated administration of caffeine induces either sensitization or tolerance of locomotor stimulation depending on the environmental context. Pharmacol Rep. 2012;64:70-77.  [PubMed]  [DOI]
53.  Scott D, Blizzard L, Fell J, Jones G. Prospective study of self-reported pain, radiographic osteoarthritis, sarcopenia progression, and falls risk in community-dwelling older adults. Arthritis Care Res (Hoboken). 2012;64:30-37.  [PubMed]  [DOI]
54.  Kemmler W, Teschler M, Goisser S, Bebenek M, von Stengel S, Bollheimer LC, Sieber CC, Freiberger E. Prevalence of sarcopenia in Germany and the corresponding effect of osteoarthritis in females 70 years and older living in the community: results of the FORMoSA study. Clin Interv Aging. 2015;10:1565-1573.  [PubMed]  [DOI]
55.  Toda Y, Kobayashi T. The usefulness of walking for preventing sarcopenia in dieting postmenopausal women complaining of knee pain. Ann N Y Acad Sci. 2000;904:610-613.  [PubMed]  [DOI]
56.  Fusaro I, Orsini S, Stignani S, Creta D, Cava FC, Benedetti MG; Società Italiana di Chirurgia della Spalla e del Gomito. Proposal for SICSeG guidelines for rehabilitation after anatomical shoulder prosthesis in concentric shoulder osteoarthritis. Musculoskelet Surg. 2013;97 Suppl 1:31-37.  [PubMed]  [DOI]
57.  Karlsson MK, Karlsson C, Magnusson H, Cöster M, von Schewelov T, Nilsson JA, Brudin L, Rosengren BE. Individuals with primary osteoarthritis have different phenotypes depending on the affected joint - a case control study from southern sweden including 514 participants. Open Orthop J. 2014;8:450-456.  [PubMed]  [DOI]
58.  Lee SY, Ro HJ, Chung SG, Kang SH, Seo KM, Kim DK. Low Skeletal Muscle Mass in the Lower Limbs Is Independently Associated to Knee Osteoarthritis. PLoS One. 2016;11:e0166385.  [PubMed]  [DOI]
59.  Aguiar R, Sequeira J, Meirinhos T, Ambrósio C, Barcelos A. SARCOSPA - Sarcopenia in spondyloarthritis patients. Acta Reumatol Port. 2014;39:322-326.  [PubMed]  [DOI]
60.  Toussirot E, Michel F, Wendling D. Bone density, ultrasound measurements and body composition in early ankylosing spondylitis. Rheumatology (Oxford). 2001;40:882-888.  [PubMed]  [DOI]
61.  Plasqui G, Boonen A, Geusens P, Kroot EJ, Starmans M, van der Linden S. Physical activity and body composition in patients with ankylosing spondylitis. Arthritis Care Res (Hoboken). 2012;64:101-107.  [PubMed]  [DOI]
62.  El Maghraoui A, Ebo'o FB, Sadni S, Majjad A, Hamza T, Mounach A. Is there a relation between pre-sarcopenia, sarcopenia, cachexia and osteoporosis in patients with ankylosing spondylitis? BMC Musculoskelet Disord. 2016;17:268.  [PubMed]  [DOI]
63.  Dos Santos FP, Constantin A, Laroche M, Destombes F, Bernard J, Mazières B, Cantagrel A. Whole body and regional bone mineral density in ankylosing spondylitis. J Rheumatol. 2001;28:547-549.  [PubMed]  [DOI]
64.  Liu C, Wang H, Tang X, Guan Z, Reid BJ, Rajapaksha AU, Ok YS, Sun H. Biochar increased water holding capacity but accelerated organic carbon leaching from a sloping farmland soil in China. Environ Sci Pollut Res Int. 2016;23:995-1006.  [PubMed]  [DOI]
65.  Caimmi C, Caramaschi P, Venturini A, Bertoldo E, Vantaggiato E, Viapiana O, Ferrari M, Lippi G, Frulloni L, Rossini M. Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis. Clin Rheumatol. 2018;37:987-997.  [PubMed]  [DOI]
66.  Marighela TF, Genaro Pde S, Pinheiro MM, Szejnfeld VL, Kayser C. Risk factors for body composition abnormalities in systemic sclerosis. Clin Rheumatol. 2013;32:1037-1044.  [PubMed]  [DOI]
67.  Wang C, Bai L. Sarcopenia in the elderly: basic and clinical issues. Geriatr Gerontol Int. 2012;12:388-396.  [PubMed]  [DOI]
68.  Skoie IM, Dalen I, Ternowitz T, Jonsson G, Kvivik I, Norheim K, Omdal R. Fatigue in psoriasis: a controlled study. Br J Dermatol. 2017;177:505-512.  [PubMed]  [DOI]
69.  Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Placek W. Fatigue - an underestimated symptom in psoriatic arthritis. Reumatologia. 2017;55:125-130.  [PubMed]  [DOI]
70.  Meng NH, Li CI, Liu CS, Lin CH, Lin WY, Chang CK, Li TC, Lin CC. Comparison of height- and weight-adjusted sarcopenia in a Taiwanese metropolitan older population. Geriatr Gerontol Int. 2015;15:45-53.  [PubMed]  [DOI]
71.  Ferrando B, Olaso-Gonzalez G, Sebastia V, Viosca E, Gomez-Cabrera MC, Viña J. Allopurinol and its role in the treatment of sarcopenia. Rev Esp Geriatr Gerontol. 2014;49:292-298.  [PubMed]  [DOI]