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THE RELATIONSHIP BETWEEN ARTHRITIS AND MUSCULAR STRENGTH IN OLDER WOMEN WITH SYMPTOMS OF SARCOPENIA

 

E.N. Renna1, S.G. Slezak1, K.B. Mahoney1, I.E.Lofgren2, D.L. Hatfield1, M.J. Delmonico1, F. Xu1

 

1. Department of Kinesiology, University of Rhode Island; 2. Department of Nutrition and Food Sciences, University of Rhode Island

Corresponding Author: Furong Xu, Department of Kinesiology, University of Rhode Island, Independence Square II, 25 West Independence Way, Kingston, RI 02881. Email: fxu2007@uri.edu. Fax: 401-874-4215, Telephone: 401-874-2412

J Aging Res Clin Practice 2017;6:217-222
Published online October 26, 2017, http://dx.doi.org/10.14283/jarcp.2017.29

 

Abstract

Background: Sarcopenia classification is important for prevention or intervention of sarcopenia in the elderly.  However, measures used for the current sarcopenia criteria, including muscular strength, could be impacted by forms of arthritis.  Thus, it is crucial to understand the impact arthritis has on sarcopenia status. Objectives: The aim was to investigate if arthritis relates to sarcopenia classification via grip strength or single chair stand in older women. A secondary aim was to assess the relationship between grip strength and upper and lower body strength in those with arthritis. Design: A cross-sectional analysis. Setting and participants: Sixty-one community-dwelling older women (71.9±4.6 years) from Rhode Island. Measurements: Sarcopenia status was classified using established working definitions. Grip strength was measured using a hand grip dynamometer, chair stands were measured via a single chair stand test, and gait speed was assessed using a four-meter walk test.  A segmental multi-frequency bioelectrical impedance analysis assessed body composition and arthritis status was based on self-report. Upper and lower body muscular strength were measured using a chest press and leg press one repetition maximum. Results: No associations were observed between arthritis and sarcopenia status (p=0.36) nor arthritis and upper or lower body muscular strength and grip strength. Conclusions: The results of this study may indicate that arthritis is not associated with sarcopenia status but may affect other measures of muscular strength.

Keywords: Sarcopenia, Arthritis, Muscular Strength, Older Women.

 

 

Introduction

Sarcopenia is defined as the loss of muscular strength, functionality, and lean mass with aging (1, 2) that is related to functional limitations (3). This is especially a concern among older women since women have a greater life expectancy and are at higher risk for functional disability due to more rapid declines in muscular strength when compared to men (4).  As a result of that, sarcopenia also has a great impact on health care with estimated costs for women around $25.5 billion in the U.S. and continues to increase as the older population increases (4, 5). Therefore, it is imperative to screen women for sarcopenia so proper intervention and prevention can be implemented.  While a universal sarcopenia classification system is lacking, several national and international organizations have established working classification systems for sarcopenia that include measures of muscular strength, gait speed and lean mass (1, 6-8).
While organizations have various criteria for sarcopenia, muscular strength is often assessed using a grip strength test because it is considered a valid measure to predict overall muscular strength.  It is also easier to administer to large populations due to its compact size and portability (1, 9-12). Some working definitions use alternative measures to assess muscular strength such as chair stands.  The International Working Group uses this measure in their working definition because the ability to rise from a chair is considered an activity of daily living that requires adequate muscular strength (7, 13).  However, functional limitations such as arthritis could negatively affect muscular strength measurements based on the current sarcopenia working definitions.
Arthritis is a chronic disease characterized by joint stiffness, inflammation, joint deformity, and pain (14).  In the U.S., arthritis is the most common cause of disability (15).  Between 2013 and 2015, approximately 54.4 million adults were diagnosed with arthritis (15).  The symptoms of arthritis (i.e. joint pain, inflammation) could affect one’s ability to perform muscular strength tests.  Since muscular strength is a key component of all sarcopenia working definitions, it is important to address the potential misclassification of sarcopenia due to the limitations in physical function arthritis may cause (14).  Therefore, the purpose of this study was to determine if arthritis is related to sarcopenia classification via grip strength or failure to complete a chair stand in older women.  A secondary aim was to assess if grip strength was related to upper and lower body muscular strength in a group of older women with symptoms of sarcopenia by arthritis status.

 

Materials and methods

Study Design

The study utilized a cross-sectional analysis to assess the potential effects of arthritis on sarcopenia status in elderly women who were recruited for Resistance Exercise Study to Reclaim Lean Muscle and Strength (URI RESTORE ME). It was approved by the University of Rhode Island’s Institutional Review Board.

Participants

Participants were recruited from Rhode Island via flyers, community talks and word of mouth, and Figure 1 depicts the flow of participant recruitment.  One hundred sixty women were initially phone screened for study eligibility based on the inclusion and exclusion criteria for the study (Table 1).  Participants who initially qualified provided written informed consent and were tested for sarcopenia using the European Working Group on Sarcopenia in Older People (EWGSOP) (1), the International Working Group (IWG) (7), and the Foundation for the National Institutes of Health Sarcopenia Project (FNIHSP) criteria (6,8).

Table 1 Inclusion and exclusion criteria used for study recruitment

Table 1
Inclusion and exclusion criteria used for study recruitment

 

Outcome Measures

Anthropometrics

Participants had their height, weight, and waist and hip circumferences measured twice.  Participants wore surgical scrubs for the waist and hip circumference measurements assessed using standard tape measure with a tensiometer (Gulick Tape Measure, Japan).  Weight was measured using a Seca balance beam scale to the nearest 0.1 kg and height was measured using a Seca wall mounted stadiometer (Seca, Chino, CA) to the nearest 0.1 cm. Both measurements were done without shoes and were performed two times.  The average of the two scores was used to calculate each participant’s BMI and waist-to-hip ratio.
Body composition was also assessed using an InBody 570 SMF-BIA (Biospace Co, Ltd, Korea) device according to the manufacturer’s instructions.  The SMF-BIA is an accepted valid device used to estimate lean mass and is safe to use in older populations (16).  This device has been found to be agreeable to dual energy x-ray absorptiometry (DXA) measurements of appendicular lean mass in this population (17).  Measurements were taken at the right and left arms, the right and left legs, as well as for the trunk using 8 electrodes specifically placed and 6 different frequencies (1 kHz, 5 kHz, 50 kHz, 250 kHz, 500 kHz, 1000 kHz) which gave a total of 30 impedance measurements for each participant. To standardize the assessment, all participants were asked to be hydrated and fasted for at least four hours and their bladder voided prior to testing.

Sarcopenia Status

The EWGSOP (1), IWG (7), and FNIHSP (6,8) working definitions were used to determine participants’ sarcopenia status based on their performance in a hand grip strength test, a single chair stand, gait speed, and their appendicular lean mass (ALM) as measured using a segmental multi-frequency bioelectrical impedance analysis (SMF-BIA, InBody 570 SMF-BIA, Biospace Co, Ltd, Korea) device.  Based on those three working definitions, our criteria for study inclusion were: <20 kg for grip strength or inability to complete a single chair stand, a gait speed <0.8m/s, and an ALM < 5.67 kg/m2 or ALM/body mass index (BMI) <0.512. Women were then classified as having low muscular strength, low lean mass, low physical functioning (gait speed), all three aspects, or none if no criteria were met.  Participants were also considered either grip dependent or non-grip dependent depending on their grip strength score.  Participants were considered grip dependent if they only met the muscular strength criteria (<20kg or inability to do a single chair stand) and were considered non-grip dependent if they exceeded the muscular strength criteria or met the other criteria or met no criteria.

Determining Arthritis Presence

Arthritis was based on self-report noted in participants’ phone screening interviews and medical history questionnaires administered during testing sessions.  The medical history questionnaire used a “yes/no” question to identify if the participant had arthritis.

Physical Function

A four-meter gait speed test was used to measure lower extremity functionality (1).  Participants walked at a normal walking pace over the four meters for two trials. Participants were hand timed for both trials, and the fastest time was used. Lower extremity function was also assessed using a single chair stand (7,13).  Participants were asked to complete a single chair stand unassisted with arms crossed over their chest for one trial.  Participants who were unable to stand successfully unassisted were considered to have low muscular strength.

Muscle Function and Strength

Hand grip strength is used to measure muscular strength (18).  It is a key factor in the current working definitions for sarcopenia (1,8), and is a reliable and valid measure for the older adult population (18).  Grip strength was assessed using a hand grip dynamometer (Jamar Hydraulic Dynamometer, J.A. Preston Corp., Jackson, MS).  Participants were seated with the elbow flexed at 90 degrees.  The hand grip dynamometer was adjusted for each participant by ensuring all four fingers had the second knuckle placed flat on the handle. Two trials were completed on each hand with the highest score being recorded in kilograms.  Grip strength was measured during testing sessions and at the baseline assessment.
A chest press machine (Cybex International, Inc., Medway, MA) was used to assess maximum upper body strength via a one repetition maximum test (1RM) for each participant employing methods previously published (19).  From a seated position, participants had their head, shoulders, and back against a seat back and held onto handles positioned at chest height.  Participants then extended their elbows fully and then returned to the starting position to assess their chest press 1 RM (CP1RM).  A 1RM for lower body muscular strength (LP1RM) for each participant was determined using a seated leg press machine (Cybex International, Inc., Medway, MA) using methods previously published (20).  Briefly, participants were seated and then extended their knees from the starting position (~90 degrees) by pushing against a platform with their feet until their knees were close to full extension but not locked.  For both CP1RM and LP1RM, after a standard warm up, participants completed 3-5 sets of one repetition with a gradual increase in weight and a three-minute rest period between sets until their 1RM was determined.

Other measures

The Yale Physical Activity Survey (YPAS) questionnaire was administered to evaluate participants’ baseline physical activity levels and has been shown to be a valid assessment for determining physical activity levels among older adults (21).  This questionnaire was used for describing participants’ baseline physical activity levels (21).
The Dietary Screening Tool (DST) was administered to participants at baseline testing to assess their dietary patterns and to determine their level of nutritional risk.  There are three levels of nutritional risk that are used to identify if older adults are at risk including: at risk (<60), at possible risk (60-75), and not at risk (>75) (22).  This questionnaire was used to describe the baseline characteristics for the participants who partook in baseline testing for the randomized controlled trial.

Statistical Analysis

Estimated sample size for this study was determined based on anticipated between-group changes in lean mass rather than change in sarcopenia status by arthritis prevalence.  This analysis was part of a larger pilot study to determine the potential for periodized resistance training to impact sarcopenia.  The demographic and clinical characteristics for participants are expressed as mean ± standard deviation for continuous variables and frequencies for categorical variables.  A Shapiro-Wilk test was completed to test for normal distribution. Independent samples t-tests were used to compare those with arthritis to those without arthritis.  A Fisher’s exact test was used to assess arthritis status and its association to sarcopenia status via multiple sarcopenia definitions for women who were screened (n=61).  A Pearson correlation was used to assess the correlation between grip strength, CP1RM, and LP1RM in those with arthritis and those without arthritis from participants who partook in the baseline assessments (n=25).  An alpha of p≤0.05 was used for all statistical analyses and all analyses were performed using SPSS software (IBM SPSS, Version 22, Armonk, NY, 2013).

 

Results

Of the 160 women initially interested, 61 women (mean age 71.9±4.60 years) qualified for further testing after preliminary phone screening.  Of those 61 women, 35 women had arthritis and 26 of those women did not have arthritis.  Additionally, 25 women (mean age 72.2±4.6 years) out of the 61 women, who qualified for the URI RESTORE ME study, exhibited at least one symptom or sign of sarcopenia defined by various working group definitions and completed all baseline measurements for the URI RESTORE ME study.  Of the 25 women, 15 women had arthritis and 10 women did not have arthritis.  Tables 2 and 3 describe the sample characteristics by sarcopenia criteria, age, 1RM measures, physical activity scores, and DST scores. There were no significant differences in characteristics between those with arthritis to those without arthritis.
When evaluating the association between arthritis and sarcopenia status via grip strength or a single chair stand, arthritis was not significantly related to sarcopenia status via multiple definitions (n=61, p=0.36). Additionally, when assessing maximal muscular strength measures for the women (n=25) who partook in the baseline testing for the URI RESTORE ME study with arthritis, there were no significant correlations between grip strength and CP1RM (r=-0.226, p=0.438), grip strength and LP1RM (r=-0.118, p=0.688), and CP1RM and LP1RM (r=0.389, p=0.152).  However, for those without arthritis, there was a significant correlation between grip strength and CP1RM (r=0.683, p=0.029), CP1RM and LP1RM (r=0.881, p=0.001), but not between grip strength and LP1RM (r=0.554, p=0.097).

 

Table 2 Characteristics of those with arthritis and without arthritis in participants who completed the testing measurements for the randomized controlled trial (n=61)

Table 2
Characteristics of those with arthritis and without arthritis in participants who completed the testing measurements for the randomized controlled trial (n=61)

*BMI, Body Mass Index; †% Body Fat measured using InBody 570 SMF-BIA, Biospace Co, Ltd, Korea; ‡Number of people who passed, n(%); P-values were obtained using independent samples t-tests; §p value was obtained using a Fisher’s Exact Test.

 

Table 3 Characteristics of those with arthritis and without arthritis for participants who completed baseline measurements for the randomized controlled trial (n=25)

Table 3
Characteristics of those with arthritis and without arthritis for participants who completed baseline measurements for the randomized controlled trial (n=25)

*BMI, Body Mass Index; DST, Dietary Screening Tool; †% Body Fat measured using InBody 570 SMF-BIA, Biospace Co, Ltd, Korea;  ‡Physical Activity (PA) from the Yale Physical Activity Survey (YPAS); YPAS and PA Index mean±SD reflect n=24 due to incomplete/missing surveys; §Dietary Screening Tool: At Risk (<60), Possible risk (60-75), Not at risk (>75), mean±SD reflect n=23 due to incomplete/missing surveys; || Number of people who passed, n(%); p-values were obtained using independent samples t-tests; { p-value was obtained using a Fisher’s Exact Test.

 

Figure 1 Study Flow Chart

Figure 1
Study Flow Chart

 

Discussion

 

The results of the present study indicate that arthritis was not associated with sarcopenia status in this population of older women based on multiple sarcopenia working definitions.  Additionally, our results showed that there was no correlation between grip strength and both upper and lower body muscular strength for those with arthritis.
Contradictory to our findings, a study by Kemmler et al (2016) used a cross-sectional analysis to compare osteoarthritis in the hip and lower limb to sarcopenia status in older women and found that those with osteoarthritis were more likely to be sarcopenic than their non-arthritic counterparts (23).  However, that study focused only on osteoarthritis in the lower half of the body while we assessed general arthritis to all components of the working definitions (23).  Additionally, unlike our present study, that study did not take into consideration other working definitions of sarcopenia and only used the EWGSOP definition.  Our study on the other hand, used the EWGSOP, IWG, and FNIHSP working definitions and utilized the single chair stand component of the IWG definition as well as grip strength for measures of muscular strength.  The IWG uses this measure because it is an important activity of daily living and requires adequate muscular strength.  In our study, we only had one participant who could not perform a chair stand but displayed no other symptoms of sarcopenia despite reporting arthritis.  Although we do not know of the kind of arthritis or what joints were affected, it is possible that arthritis could have impaired her ability to perform the chair stand.  Poor muscular strength in the lower limbs is known to promote cartilage damage which could progress any current osteoarthritis (24). Future studies need to address both arthritis and sarcopenia together and the potential affects each has on the other. The lack of studies in this area could be due to having high internal validity and therefore not accurately capturing the older adult population.
This study also looked at the relationship between grip strength and upper and lower body muscular strength for those with and without arthritis.  This relationship is important because grip strength is often used to assess overall muscular strength as it is more convenient in a clinical setting and easier to administer compared to other muscular strength tests such as 1 RM testing (11).  However, the present study found correlations between grip strength and upper and lower body muscular strength for non-arthritis participants but not those with arthritis.  This is not consistent with other findings in the literature.  Other studies have reported that grip strength and lower body strength as well as grip strength and upper body strength are related, and that using grip strength as a measure for overall muscular strength is an adequate alternative (11,25,26).   Yet, those studies only used healthy volunteers while our study evaluated both participants with and without arthritis.  Therefore, given the results of our study, it is possible that arthritis played a role in the lack of relationship, and arthritis may have attenuated participants’ ability to perform the strength tests (11).  This could be due to characteristics of arthritis such as pain, inflammation, and functional limitations (27,28).
This study has limitations and strengths.  First, the sample size of our study was small and therefore, the results may not adequately reflect this association.  Additionally, we did not focus on one specific type of arthritis but rather included all forms of arthritis. Despite these study limitations, this study also has strengths worth noting.  First, to our knowledge this is the first study to assess general arthritis and its relationship to sarcopenia status via grip strength and single chair stands in older women with or without symptoms of sarcopenia based on multiple sarcopenia guidelines.  While other studies have evaluated specific types of arthritis or used only one working definition in their research.  Secondly, this study included a homogenous sample cohort of community-dwelling older women.  Finally, this study used measures of muscular strength that have been standardized and validated for older populations (19, 20).

 

Conclusions

This is the first study to evaluate the impact arthritis has on grip strength or failure to complete a single chair stand in a population of older women for the classification of sarcopenia using multiple sarcopenia guidelines.  The present study found that arthritis was not significantly associated with sarcopenia status via grip strength or single chair stand and that there is no significant correlation between grip strength and both upper and lower body muscular strength in older women with arthritis.  Although this pilot study adds to the literature, additional studies with a larger sample size and clearly defined arthritis status (i.e. joints affected and type) are needed to determine if these variables are linked and to further explore the lack of the relationship between muscular strength measures.

 

Funding: This study was funded by a grant from the College of Health Sciences at the University of Rhode Island.

Acknowledgments: : The authors would like to extend their gratitude to all study participants and University student volunteers for their support.

Conflict of interest: The authors declare that there no conflict of interest.

Ethical standard: All procedures performed in this study were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

 

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PLASMA LEVELS OF INTERLEUKIN-6 AND SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR ARE ASSOCIATED WITH MUSCLE PERFORMANCE IN PRE-FRAIL COMMUNITY-DWELLING OLDER WOMEN?

 

L. Paccini Lustosa1, L. Souza Máximo Pereira1, P.Parreira Batista2, D.A. Gomes Pereira1, J.M. Domingues Dias1, A. Netto Parentoni3

 

1. PhD, Prof. Physiotherapy Department, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; 2. Post-graduate program in Rehabilitation Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; 3. PhD, Prof. Physiotherapy Department, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, MG, Brazil.

Corresponding Author: Lygia Paccini Lustosa, Av. Prof. Antonio Carlos, 6627 – Pampulha – Belo Horizonte – Minas Gerais – Brazil, Cep: 31.270-901 –e-mail: lygia.paccini@gmail.com – tel.: 55 (31) 99831854/ 34094791

J Aging Res Clin Practice 2016;inpress
Published online September 1, 2016, http://dx.doi.org/10.14283/jarcp.2016.113

 

Abstract

Aim: Increased plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α have been associated with frailty syndrome and reduced muscle strength in older. Sarcopenia influenced loss of mobility and functional independence, and contributed to frailty syndrome. Furthermore, sarcopenia mainly entails a decrease in type II muscle fibers, with consequent loss of muscle power; this could occur as a result of a lack of physical activity. Objective: To examine the correlation of muscular performance and the plasma levels of IL-6 and soluble TNF receptor (sTNFr) in pre-frail community-dwelling women. Methods: The study included 32 pre-frail women (≥ 65ys). The measurements were plasma concentrations of IL-6 and sTNFr1 (ELISA); muscle strength (isokinetics Biodex System). The muscle resistance program constituted 75% of maximum load (3 times/week, 10 weeks). Statistical analysis were made through Pearson and Spearman correlation (α = 5%). Results: There was a significant inverse correlation between sTNFr1 and muscle strength, pre- (r = −0.36, P = .04) and post-training (r = −0.37, P = .04) and, a significant positive correlation between IL-6 and muscle strength (r = 0.45, P = .01). Conclusion: The correlations found between the inflammatory mediators and the measures of muscular performance evaluated before and after training suggest that, as the muscles increase their ability to generate power, sTNFr concentrations decrease, and the levels of IL-6 increase. Muscle resistance exercises should be encouraged in pre-frail older women to induce the release of cytokines.

Key words: Frail, older women, IL-6, sTNFr, exercise.

 

Introduction

Sarcopenia is a term used to describe a degeneration of the musculoskeletal system, which can be related to changes in the immune and endocrine systems, among others (1, 2). Sarcopenia mainly entails a decrease in type II muscle fibers, with consequent loss of muscle power; this could occur as a result of a lack of physical activity (3-7). Moreover, sarcopenia may have a greater health impact on older women than men, as women have a longer life expectancy and greater rates of morbidity (7, 8). Schaap et al (2006) reported a positive correlation between sarcopenia and elevated plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-reactive protein, and tumor necrosis factor-alpha (TNF-α) (4). Doherty (2003) reported that sarcopenia influenced loss of mobility and functional independence, and contributed to frailty syndrome (6). Frailty syndrome has been described as a clinical, multi-factorial syndrome characterized by 3 distinct actions: deregulation of the neuroendocrine system, deregulation of the immune system, and the induction of sarcopenia (9, 10). Thus, sarcopenia may be associated with a sub-threshold state of chronic inflammation that is characteristic of older people (11).
Ferrucci et al (2002) concluded that the reduced ability to perform daily functional activities was associated with high levels of IL-6 and TNF-α, and the loss of muscular strength (12). These authors pointed to the deleterious effect of high concentrations of these cytokines in muscle tissue. Previous studies in our laboratory have demonstrated an inverse correlation between plasma IL-6 levels and muscle strength of lower limbs and hand grip in institutionalized older individuals at rest (13, 14). Pereira et al (2009) and Oliveira et al (2008) found an inverse correlation between manual and knee extensor muscle strength with plasma levels of IL-6 (15,16). Greiwe et al (2001) reported that an increase in plasma levels of TNF-α is associated with loss of muscle mass, and that concentric resistance exercises could reduce plasma expression of this cytokine in their older participants (17).
In this context, some authors have suggested that physical activity, or a program of specific resistance exercises, could reduce the plasma levels of pro-inflammatory mediators and possibly reduce the deleterious consequences of these cytokines in musculoskeletal tissue (5, 13, 17-19). The explanation behind this hypothesis relates to the fact that IL-6 can be released by muscle contraction (named myokine), independently of TNF-α, thereby inducing the release of other anti-inflammatory cytokines (IL-10 and IL-1ra) that could reduce plasma concentrations of TNF-α (5, 17-20). These assumptions are even more significant when considering the muscular and inflammatory systems of older individuals with frailty syndrome. Moreover, a recent study demonstrated an improvement in muscle strength and function after a resistance exercise program, but no changes in inflammatory mediators following the program. However, discontinuation of this program increased the plasma levels of TNF-α (21).
The objective of this study was therefore to assess the correlation between the muscle strength of knee extensors and plasma indexes of IL-6 and sTNFr1, before and after a resistance exercise program for the lower limbs in pre-frail older women.

 

Methods

This study was a cross-sectional analysis as part of a randomized, blind, crossover clinical trial approved by the Research Ethics Committee of Universidade Federal de Minas Gerais, decree ETIC 321/2007. The protocol for this study was registered in BioMed Central (BMC) under number ISRCTN62824599 (http://www.controlled-trials.com/ISRCTN62824599). All participants signed an informed consent form before starting the study, and were recruited from the clinics of 2 universities, through verbal invitation.  After the initial evaluation, the participants started training (3 times/week, for 10 weeks) at 75% of maximal load. The physiotherapist responsible for the intervention had no knowledge of the evaluations performed. The evaluators had no knowledge of the group to which each participant belonged (21, 22).

Sample

Thirty-two community-dwelling older women (aged 65 years and older) were selected; pre-frail criteria, according to the phenotype proposed by Fried et al (2010) were used.2 All participants answered a questionnaire aimed to characterize the sample in terms of clinical and socio-demographic aspects.
Exclusion criteria were cognitive impairment (Mini Mental State Exam, 1994) (23), orthopedic and neurological diseases that could affect test outcomes, acute inflammatory disease, cancer, and use of drugs that act on the immune system.

Measuring Instruments

The plasma levels of IL-6 and sTNFr1 were measured by enzyme-linked immunosorbent assay using high sensitivity kits (Quantikine®HS, R&D Systems, Minneapolis, USA). The samples were analyzed by a micro-plate reader set to 490 nm and corrected for wavelength at 650 nm. The blood sample analyses of plasma concentrations of IL-6 and sTNFr1 were performed on different days from the muscle tests, with at least a 48-h interval and always in the morning between 8 and 10 am. A qualified professional performed the blood collection, following the necessary standards and procedures. Five milliliters of blood was collected and centrifuged at 1,500 rpm for 15 min to separate the plasma. The plasma was properly identified and stored in a freezer at −70°C. The analyses were performed in duplicate, and the results were presented as the average of the 2 measures ± standard deviation, in pg/ml.
The muscle performance of the knee extensor muscles were measured by an isokinetic dynamometer (Biodex System 3 Pro®) at an angular velocity of 60º/s and 180º/s. At each velocity, 3 training repetitions at sub-maximal effort were used to familiarize the participants with the procedure. The isokinetic evaluation was conducted by measuring 5 and 15 repetitions at maximum effort, at angular velocities of 60º/s and 180º/s, respectively. Participants were motivated during the test by using clapping and verbal encouragement. This standardized version of the test has been used in previous studies [16]. For the analyses, the variable, i.e. work, was standardized by body weight, average power, and peak torque at the angular velocities of 60º/s and 180º/s.

Intervention

The resistance exercise program was conducted during a period of 10 weeks, with 3 sessions per week. Each session consisted of exercises performed in groups of 4−6 participants, with direct guidance and supervision by a physiotherapist. The exercises targeted the lower limbs, particularly the knee extensors, using open and closed kinetic chain exercises, and a load of 75% of the participant’s maximal load (24). The choice of exercises and program dynamic was based on previous studies (24) and is in agreement with the previously published study protocol (25).

Statistical Analysis

The sample size was calculated considering a confidence interval of 95%, an alpha (α) value of 5%, and a standard error of 20%. To test for the normality of the data, the Anderson Darling test was performed, and a Box Cox transformation for optimal lambda (λ) was done for the IL-6 variable as it was not normally distributed. The correlations between variables were made by Pearson and Spearman correlation test. The level of significance was set at α = 5%.

 

Results

This study included 32 pre-frail older women. All volunteers were classified as pre-frail, according to criteria described by Fried et al (1, 2) and 16 (1 in 2 cases) out of the 32 older women evaluated had 2 positive criteria. The most prevalent criteria were reduction in hand grip strength (43.8%), low caloric expenditure (43.8%), reduction in gait speed (34.4%) and reported exhaustion (25%). The clinical and demographic characteristics of each group are shown in Table 1.

 

 

Table 1 Demographic and characteristics of participants

Table 1
Demographic and characteristics of participants

SD, standard deviation; MEEM,Mini Mental State Exam

 

The analyses of correlation were done before and after the exercises. Before training, there was a poor but significant inverse correlation between the plasma concentration of sTNFr1 and work, which was standardized by body weight in the angular velocity of 180º/s (r = −0.36, P = .04), peak torque at 180º/s (r = −0.38, P = .03) and average power at 180º/s (r = −0.40, P = .02), showing that sTNFr1 concentrations were lower when the power, peak torque, and average power increased (Table 2). After exercises, there was a poor but significant inverse correlation between the concentration of sTNFr1 and the measures of standardized work by body weight and average power at 180º/s (r = −0.37, P = .04; r = −0.37, P = .04, respectively).
Furthermore, there was a positive significant correlation between the plasma concentration of IL-6 and the peak torque and average power at 60º/s (r = 0.45, P = .01; r = 0.44, P = .01, respectively) and at 180º/s (r = 0.46, P = .01; r = 0.37, P = .04, respectively). These results showed an increase in IL-6 associated with an increase in peak torque and muscle power, suggesting that this cytokine was released after training (Table 2).
The statistical analyses showed improvement on the muscular power and on the functional capacity after training period, but there was no difference on the inflammatory mediators (data not shown, but previously published). Likewise, after the period of 10 weeks of follow-up there was statistical difference on the sTNFr measures (data not shown, but previously published) (21).

 

 

Table 2 Correlation between sTNFr1 and IL-6 with muscular variables, pre- and post-intervention

Table 2
Correlation between sTNFr1 and IL-6 with muscular variables, pre- and post-intervention

* Significant difference; IL-6, interleukin-6; sTNFr, soluble tumor necrosis factor receptor.

 

Discussion

The aim of this study was to assess the correlation between the muscle strength of knee extensors and plasma indexes of IL-6 and sTNFr1 before and after a resistance exercise program for the lower limbs in pre-frail older women. The results showed that there was a significant inverse correlation between sTNFr1 and the muscle strength parameters, before and after training. Furthermore, a significant positive correlation between IL-6 and the muscle parameters was detected after training, indicating a probable anti-inflammatory effect of IL-6 released by muscular contraction after resistance exercises.
These findings are in agreement with the results of some authors who suggested using the term myokine for the cytokines that are released by muscle contraction, in particular, IL-6 (11, 19, 20). According to these authors, in response to muscle contraction, type I and II fibers induce the release of IL-6 (11, 19, 20). Thus, this cytokine would exert a local effect on the muscle, and peripheral effects via the induction and inhibition of other pro- and anti-inflammatory cytokines, thereby increasing glucose levels, which are needed for muscle contraction and fat oxidation (18, 19, 26, 27). In this context, there is evidence of an increase in IL-1ra and IL-10 and a reduction in TNF-α after physical exercise, suggesting that exercise has anti-inflammatory effects (19, 21, 28). Therefore, the significant correlations found in this study are in agreement with the literature, showing that greater muscular performance is associated with lower concentrations of sTNFr and higher concentrations of IL-6.
Another argument about these associations has been suggested, concerning the mechanism of this phenomenon. Febbraio et al (2002) and Petersen et al (2005) showed that the plasma levels of IL-6 tend to increase in response to an increase in adrenal sympathetic response induced by the β-adrenergic pathway (11, 19). Therefore, modifications in the glycogen available for muscle contraction would be sufficient to initiate greater release of IL-6, which, in turn, would alter levels of sTNFr (11, 19, 20). The present study did not intend to elucidate the physiological mechanisms that occur during the release of mediators, but the significant correlations that were found suggest that improved muscular performance is one factor that can modify the plasma concentrations of these inflammatory mediators. However, this hypothesis must be further investigated in future studies with an adequate methodology to explain such mechanisms.
Muscle resistance-training programs have been identified as a positive factor that influences the plasma levels of some cytokines, such as IL-6 and TNF-α (20). Febbraio et al (2002) and Petersen et al (2005) demonstrated that IL-6 can be released by muscle activation, independently of TNF-α, after performing strenuous exercise that involves large muscle groups (11, 19). These authors argued that the muscle could be considered an endocrine organ owing to its participation in the release of cytokines, having consequential endocrine and paracrine actions (11, 18, 20, 27). In this context, IL-6 can induce other anti-inflammatory cytokines (IL-10 and IL-1ra) and thereby inhibit the deleterious effects of TNF-α in muscular tissue (19, 27). Therefore, considering the association between muscle strength and inflammatory mediators, our findings suggest that there are modifications occurring in relation these cytokine mediators’ causing functional limitations before the clinical detection of loss of strength in older people. These modifications could be triggered and/or exacerbated by not performing physical activities. However, this phenomenon may also be exacerbated owing to the fluctuating condition and vulnerability of patients with frailty syndrome, which was the target sample of this study.
Finally, studies on the pathogenesis of sarcopenia are not yet conclusive. Several factors may be involved in the loss of muscle mass and strength that are inherent to aging and its association with the inability to perform some activities (2). One of the factors involved, which is currently being studied and may contribute to muscle loss, is the increase in fat between muscle fibers (27). Besides complicating the physiology of muscle contraction, obesity may also contribute to the increased plasma levels of inflammatory mediators (18, 27). Even though this study did not aim to verify the correlation between obesity and sarcopenia, the body mass index of the volunteers (29.3 kg/m2 ± 4.1 kg/m2) at basal levels suggests that this variable may have influenced the observed results. Since body mass index was not controlled for different stages of the study, this variable may be a limitation of the study. The observation that the participants were overweight and had a greater abdomen/hip circumference reinforces this hypothesis. However, at this time, a link between high body mass index and muscle strength is a speculative observation that should be investigated in future work.
The correlations found between the inflammatory mediators and the measures of muscular performance evaluated before and after training suggest that, as the muscles increase their ability to generate power, sTNFr concentrations decrease, and the levels of IL-6 increase. Physiotherapists and health professionals who investigate functional and muscular performance in older people must consider the silent activities of inflammatory mediators in their studies.

 

Acknowledgements: The authors acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico and, Fundação de Amparo à Pesquisa do Estado de Minas Gerais and, Pro-Reitoria de Pesquisa da Universidade Federal de Minas Gerais for supporting this work. The authors certify that they have complied with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle 2010, 1:7-8 (von Haeling S, Morley JE, Coats AJ and Anker SD). This study was approved by the appropriate ethics comitee (Universidade Federal de Minas Gerais, Belo Horizonte, Brazil) and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and, Fundação de Amparo à Pesquisa do Estado de Minas Gerais and, Pro-Reitoria de Pesquisa da Universidade Federal de Minas Gerais.

Disclosure: No potential conflicts of interest were signed. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

 

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