Clinical relevance of resistance training in women with fibromyalgia: a systematic review and meta-analysis

Eur J Pain. 2024;28:21–36. | 21 wileyonlinelibrary.com/journal/ejp Received: 15 November 2022 | Revised: 28 May 2023 | Accepted: 5 July 2023 DOI: 10.1002/ejp.2161 REVIEW ARTICLE Clinical relevance of resistance training in women with fibromyalgia: A systematic review and metaanalysis ÁlvaroJoséRodríguezDomínguez1 | ManuelRebolloSalas1 | RaquelChillónMartínez2 | AbelRosalesTristancho3 | JoséJesúsJiménezRejano1 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®. 1Department of Physiotherapy, University of Seville, Seville, Spain 2Department of Health and Sports, Pablo de Olavide University, Seville, Spain 3Department of Statistics and Operational Research, University of Seville, Seville, Spain Correspondence Manuel RebolloSalas, Department of Physiotherapy, University of Seville, C/ Avicena s/n, Seville41009, Spain. Email: [email protected] Abstract Background and Objective: There has been an increase in the number of papers assessing the effects of resistance training (RT) in patients with fibromyalgia. Therefore, the objective of our study was to evaluate the clinical relevance and effectiveness of RT for pain intensity, functionality and severity of the disease specifically in women with fibromyalgia through a systematic review with metaanalysis. Databases and Data Treatment: Seven databases were searched. Randomized controlled trials conducted in women over 18 years of age with fibromyalgia were included. Fifteen trials were included in the systematic review and 14 of these studies were included in the three metaanalyses performed. Study quality assessment was performed using the PEDro scale. In addition, the GRADE recommendations were used. Results: The global metaanalysis revealed statistically significant differences in the RT group versus the control group on pain intensity (SMD = −0.49; 95% CI [−0.74, −0.24], p = 0.0001), functionality (SMD = −0.23; 95% CI [0.01, 0.45], p = 0.04) and on severity of the disease (SMD = −0.58; 95% CI [−0.90, −0.26], p = 0.0005). Clinically relevant improvements in the overall outcome of the three variables studied in favour of RT were obtained. Conclusions: RT is effective to improve pain intensity, functionality and severity of the disease in women with fibromyalgia. These improvements are clinically relevant. More clinical trials of RT are needed in women with fibromyalgia to support our results due to the low strength of evidence. Significance: This systematic review with metaanalysis provides evidence that RT produces clinically relevant improvements in women with fibromyalgia. The absence of immediate benefit is often a major barrier to adherence to treatment. Our findings will help clinicians to empower patients that if they continue treatment, they will achieve improvement in their disease. 22 | RODRÍGUEZDOMÍNGUEZ et al. 1 | INTRODUCTION Fibromyalgia is a syndrome that causes widespread musculoskeletal pain, fatigue, sleep disturbances and physical disability (Andrade et al.,2020; Macfarlane et al.,2017; Marques et al., 2017; Russell et al., 2018; SarziPuttini et al., 2020). It is also related to autonomic alterations, cognitive dysfunction, hypersensitivity to external stimuli, somatic symptoms and psychiatric disorders (ArendtNielsen & GravenNielsen,2003; SarziPuttini et al.,2020) and to other diseases, such as chronic fatigue syndrome and irritable bowel syndrome (Silverwood et al., 2017; Yunus,2008). The prevalence of fibromyalgia is currently estimated to be 2%– 4% of the world's population (CaboMeseguer et al., 2017; ElizagarayGarcia et al., 2016; GalvezSánchez et al., 2019; Macfarlane et al., 2017; Marques et al.,2017; SarziPuttini et al.,2020), making it the leading cause of chronic widespread pain and the third most common musculoskeletal condition (ElizagarayGarcia et al., 2016; SarziPuttini et al., 2020). At present, it is estimated that at least 80%– 90% of people with fibromyalgia are women, so the disease mainly affects subjects of this sex (Wolfe et al.,2018). However, its aetiopathological mechanisms are still unclear (Silverwood et al.,2017). Over the last 20 years, neurobiological characteristics have been identified that correlate nociplastic pain with fibromyalgia (SarziPuttini et al.,2020); this has provided a new outlook on the diagnosis of these patients, characterized by a process of central sensitization (Cagnie et al.,2014; Desmeules et al.,2003; Meeus & Nijs,2007; Nijs & Van Houdenhove,2009; SarziPuttini et al.,2020; Yunus,2008). Central sensitization is defined as ‘amplification of neural signalling within the central nervous system resulting in hypersensitivity to pain’ (Woolf,2011) and was first linked to fibromyalgia in 1994 (Gibson et al., 1994). Clinically, fibromyalgia has many features of central sensitization: hyperalgesia, allodynia, temporal summation and hypersensitivity to external stimuli such as sounds or lights (SarziPuttini et al.,2020). Therefore, it appears that central sensitization plays an important role in these patients, but this process remains a descriptive label for the possible pathophysiological mechanism (Van den Broeke et al.,2018), and further research is required to clarify its involvement in fibromyalgia, as well as to determine its aetiopathological mechanisms. The latest EULAR (European League Against Rheumatism) recommendations on the management of fibromyalgia emphasize the importance of not resorting to medication as the first intervention measure. The only ‘strong’ evidence recommendation favours physical exercise (Macfarlane et al.,2017; SarziPuttini et al.,2020). The indication for physical exercise as a treatment modality in fibromyalgia is to prevent the inactivity and deconditioning that is often associated with pain and fatigue. This deconditioning, resulting from inactivity, can worsen the symptoms associated with fibromyalgia. Patients who engage in consistent physical exercise have been found to report fewer symptoms, better physical function and greater overall wellbeing (Fink & Lewis,2017). However, there is controversy around which exercise modality is most beneficial and the optimal dosage parameters (Andrade et al.,2018). After aerobic exercise, resistance training (RT) is the most researched exercise modality. This modality is also often called ‘strength training’ (ST). However, there are some differences. Resistance exercise is considered any exercise that causes the skeletal muscles to contract against external resistance to increase skeletal muscle strength, tone, mass or endurance. Strength exercises are specifically resistance exercises with the objective specifically to increase skeletal muscle strength (Hansen et al.,2019). People with fibromyalgia have decreased muscle strength, which contributes to the loss of functionality observed in these patients (DeSantana & Araújo,2019). This exercise modality appears to improve pain, tenderness, fatigue, sleep, depression and muscle strength in patients with fibromyalgia (Andrade et al.,2018, 2020). However, aspects related to the duration, frequency and intensity required to improve symptoms remain unknown, as protocols differ between studies, and a consensus is lacking. Classically, it was believed that training sore muscles was counterproductive (Jones,2015). However, more than 20 years ago, a growing body of evidence began to emerge that challenged the assumption that RT worsened muscle pain in people with fibromyalgia; and, conversely, that when training was customized to the individual patient's needs, it improved the severity of the disease symptoms (Albuquerque et al.,2022; Vilarino et al.,2022). Patients with chronic pain present severe structural and functional alterations in the central nervous system (Kuner & Flor,2016; Smallwood et al.,2013). Physical exercise can acutely alter brain processing and cortical inhibition, regulating the inflammatory and immune response (Sluka et al., 2018), but the practice of RT on a regular basis promotes central neuroplastic changes that are supposed to favour pain processing (Pearcey et al.,2021); while regional musculoskeletal adaptations can reduce pain by improving function and capacity of the structure (Sluka et al.,2018). However, having fibromyalgia poses a high hurdle to overcome before reaping the rewards of RT, as these patients are less physically active and have high levels of physical deconditioning. Deconditioned muscles can be a powerful pain generator due to delayed onset muscle soreness (DOMS) as a result of a natural, physiological inflammatory response that contributes to the process of muscle repair and adaptation (Jones,2015). 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 23 RODRÍGUEZDOMÍNGUEZ et al. In recent years, there has been an increase in the number of publications assessing the effects of RT in patients with fibromyalgia. However, we have not found any metaanalysis that examined the efficacy and clinical relevance of this intervention specifically in women with fibromyalgia, as it is the most affected population. The reviews and metaanalyses mentioned above were conducted in both men and women, this heterogeneity of the study sample may imply a limitation in the results, since the effectiveness of any intervention is affected by several variables and sex is one of these variables. Therefore, the objective of our study was to evaluate the clinical relevance and effectiveness of RT for pain intensity, functionality and severity of the disease in women with fibromyalgia through a systematic review with metaanalysis. 2 | METHODS 2.1 | Protocol and registration A systematic review with metaanalysis of randomized control trials was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses; Page et al.,2021). This systematic review with metaanalysis is registered in PROSPERO (International Prospective Register of Systematic Reviews; Booth et al., 2012) with code CRD42022312777. 2.2 | Data sources and searches The literature search was carried out between 24 February and 20 April 2022. With regard to the information search, the databases selected were Web of Science, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Cochrane, Physiotherapy Evidence Database (PEDro) and Dialnet. The search strategies and keywords used are shown in TableS1. To minimize publication bias, we searched Clini calTr ials.gov. Additional records were also sought by hand searching references from relevant literature reviews to supplement the database findings. 2.3 | Study selection The outcome measures considered in our study were pain intensity, functionality and severity of the disease. The criteria the studies had to meet to be included were the following: 1. Randomized controlled clinical trials published up to 20 April 2022. 2. Study conducted in women over 18 years of age with fibromyalgia according to the American College of Rheumatology (ACR) diagnostic criteria (1990/2010/2016; Wolfe et al.,1990, 2011, 2016) 3. Including RT or ST as the only intervention in any of the groups. As a comparison group, any intervention to be performed in front of the RT or ST was accepted. 4. Evaluating pain intensity, functionality and severity of the disease. 5. Published in English, Spanish, French, Italian or Portuguese. We excluded studies that combined ST or RT with another intervention (combined treatment). 2.4 | Data extraction Two authors independently carried out the selection of studies conducted and data extraction. A third author was consulted in case of disagreement. Reviewers were not blinded to information about the authors, journal of origin or results of each article reviewed. A standardized form was used for data extraction, covering participants, type of intervention, study variables and tools used, followup time and results obtained (Table1). 2.5 | Quality assessment Methodological quality was assessed using the PEDro (Maher et al.,2003). Quality review of the studies was performed by two independent assessors, with a third consulted in the event of disagreement. The included studies were classified according to scores of 9 or 10, 6 to 8 and ≤5 on the PEDro scale, which were interpreted as excellent, good and fair quality respectively (Ghai et al.,2018). 2.6 | Data synthesis and analysis Cohen's Kappa coefficient was used to quantify the degree of agreement between the two reviewers in the article selection process. This analysis was carried out with Epidat 4.2 software. Data were analysed using a qualitative synthesis and, wherever possible, a quantitative synthesis (metaanalysis). Only one study was not included in the quantitative synthesis, as it did not provide sufficient data to do so. When studies used different tools for the assessment of the same outcome measure, we calculated the 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 24 | RODRÍGUEZDOMÍNGUEZ et al. TABLE 1 Characteristics of the included studies. Study Sample PEDro score Intervention Outcome measure and followup Reported results Häkkinen et al.(2001) 21 women with FM Mean age: 38 years Exp: 11– 11 Ctrl: 10– 10 7/11 Exp: RT included squat exercise, knee and trunk extension/flexion exercises and bench press. Initially, 1 set of 15– 20 reps (40%– 60% 1RM), and then 15– 20 (70%– 80% 1RM). Each session included warm up (bicycle ergometer and stretching) Ctrl: no intervention Duration: Twice a week for 21 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— HAQ Followup at 0 and 21 weeks Pain intensity and functionality were significantly improved in RT Jones et al.(2002) 68 women with FM Mean age: 48 years Exp: 34– 28 Ctrl: 34– 28 7/11 Exp: The main muscle groups were worked, but exercises were not specified. Initially, 1 set of 4– 5, and then to 12. Each session concluded with 10 min cooldown and stretching Ctrl: Supervised stretching program Stretches targeted the same 12 major muscle groups as the strengthening group Duration: Twice a week for 12 weeks (1) Pain intensity— FIQ pain, VAS (0– 10) (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 12 weeks Pain intensity and severity of the disease improved significantly in RT Valkeinen et al.(2004) 26 women with FM Mean age: 59 years Exp: 13– 13 Ctrl: 13– 13 6/11 Exp: The main muscle groups were worked, but exercises were not specified. Initially, 3 sets of 15– 20, and then to 4 sets of 8– 12 and 5 sets of 5– 10 Ctrl: no intervention Duration: Twice a week for 21 weeks (1) Functionality— (HAQ) Followup at 0 and 21 weeks Functionality improved in RT Kingsley et al.(2005) 29 women with FM Mean age: 46 years Exp: 15– 8 Ctrl: 14– 12 9/11 Exp: RT included chest press, leg extension, standing leg curl, shoulder press, lumbar extension, abdominal Crunch, lowpulley biceps curl, highpulley triceps extension, midpulley standing row, standing calf raises and body weight swiss ball squats. 1 set of 8– 12 (60%– 80% 1RM) Ctrl: No intervention (waitlisted for exercise) Duration: Twice a week for 12 weeks (1) Functionality— CSPFP (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 12 weeks • Functionality improved significantly in RT • Severity of the disease did not change Bircan et al.(2008) 30 women with FM Mean age: 47 years Exp: 15– 13 Ctrl: 15– 13 7/11 Exp: RT were not specified; however, free weights were used and the patient's body weight. Initially, 1 set of 4, and then to 12 reps. Each session started and concluded with 5 min of stretching Ctrl: AE comprised walking on treadmill, initially for 20 min and then 30 min as the patient tolerated. Intensity was adjusted to 60%– 70% of ageadjusted maximum heart rates Duration: Twice a week for 8 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— SF36 (physical component summary) Followup at 0 and 8 weeks Pain intensity and functionality were improved in RT Panton et al.(2009) 27 women with FM Mean age: 48 years Exp: 15– 10 Ctrl: 12– 11 7/11 Exp: RT included chest press, leg extension, leg curl, leg press, arm curl, seated dip, overhead press, seated row, abdominal crunch and low back extension. Initially, 1 set of 12 (50% 1RM), and then 1RM (100%) Ctrl: the same RT program combined with chiropractic treatment Duration: twice a week for 16 weeks (1) Functionality— CSPFP (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 16 weeks There were similar improvements in severity of the disease and functionality in both groups Kayo et al.(2011) 90 women with FM Mean age: 46 years Exp: 30– 22 Ctrl 1: 30– 23 Ctrl 2: 30– 23 6/11 Exp: RT included 11 free active exercises using free and body weight. 3 set of 10 reps, and them 3 set of 15 reps Ctrl 1: aerobic exercise (walking). Initially, 25– 30 min (40%– 50% HHR), and them 50 min (60%– 70%) Ctrl 2: no intervention Duration: three times a week for 16 weeks (1) Pain intensity— VAS (0– 10) and SF26 (bodily pain) (2) Functionality— FIQ (0– 100) and SF36 (physical function) (3) Severity of the disease— FIQ (0– 100) Followup at 0, 8, 16 and 28 weeks (7 months) All variables improved in both intervention group. Gavi et al.(2014) 80 women with FM Mean age: 46 years Exp: 40– 35 Ctrl: 40– 31 7/11 Exp: RT included leg press, leg extension, hip flexion, fly, triceps extension, shoulder flexion, abduction and extension, leg curl, calf, pulldown, biceps flexion. Three sets of 12 (45% 1RM) Ctrl: A flexibility exercise program of the major muscles, but exercises were not specified Duration: Twice a week for 16 weeks (1) Pain intensity— VAS (0– 10) (2) Functionality— SF36 (physical component summary) (3) Severity of the disease— FIQ (0– 100) Followup at 0 and 16 weeks Both groups showed improvements in the pain intensity, functionality and severity of the disease, and there was no significant difference observed between the groups Larsson et al.(2015) 130 women with FM Mean age: 51 years Exp: 67– 48 Ctrl: 63– 43 6/11 Exp: The main muscle groups were worked, but exercises were not specified. Intensity increased progressively Ctrl: Relaxation therapy approximately 25 min Duration: Twice a week for 15 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— SF36 (physical component summary) (3) Severity of the disease— FIQ (0– 100) Followup at 0 and 15 weeks, and 13 and 18 months Pain intensity, functionality and severity of the disease improved significantly in RT (Continues) 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 25 RODRÍGUEZDOMÍNGUEZ et al. TABLE 1 Characteristics of the included studies. Study Sample PEDro score Intervention Outcome measure and followup Reported results Häkkinen et al.(2001) 21 women with FM Mean age: 38 years Exp: 11– 11 Ctrl: 10– 10 7/11 Exp: RT included squat exercise, knee and trunk extension/flexion exercises and bench press. Initially, 1 set of 15– 20 reps (40%– 60% 1RM), and then 15– 20 (70%– 80% 1RM). Each session included warm up (bicycle ergometer and stretching) Ctrl: no intervention Duration: Twice a week for 21 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— HAQ Followup at 0 and 21 weeks Pain intensity and functionality were significantly improved in RT Jones et al.(2002) 68 women with FM Mean age: 48 years Exp: 34– 28 Ctrl: 34– 28 7/11 Exp: The main muscle groups were worked, but exercises were not specified. Initially, 1 set of 4– 5, and then to 12. Each session concluded with 10 min cooldown and stretching Ctrl: Supervised stretching program Stretches targeted the same 12 major muscle groups as the strengthening group Duration: Twice a week for 12 weeks (1) Pain intensity— FIQ pain, VAS (0– 10) (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 12 weeks Pain intensity and severity of the disease improved significantly in RT Valkeinen et al.(2004) 26 women with FM Mean age: 59 years Exp: 13– 13 Ctrl: 13– 13 6/11 Exp: The main muscle groups were worked, but exercises were not specified. Initially, 3 sets of 15– 20, and then to 4 sets of 8– 12 and 5 sets of 5– 10 Ctrl: no intervention Duration: Twice a week for 21 weeks (1) Functionality— (HAQ) Followup at 0 and 21 weeks Functionality improved in RT Kingsley et al.(2005) 29 women with FM Mean age: 46 years Exp: 15– 8 Ctrl: 14– 12 9/11 Exp: RT included chest press, leg extension, standing leg curl, shoulder press, lumbar extension, abdominal Crunch, lowpulley biceps curl, highpulley triceps extension, midpulley standing row, standing calf raises and body weight swiss ball squats. 1 set of 8– 12 (60%– 80% 1RM) Ctrl: No intervention (waitlisted for exercise) Duration: Twice a week for 12 weeks (1) Functionality— CSPFP (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 12 weeks • Functionality improved significantly in RT • Severity of the disease did not change Bircan et al.(2008) 30 women with FM Mean age: 47 years Exp: 15– 13 Ctrl: 15– 13 7/11 Exp: RT were not specified; however, free weights were used and the patient's body weight. Initially, 1 set of 4, and then to 12 reps. Each session started and concluded with 5 min of stretching Ctrl: AE comprised walking on treadmill, initially for 20 min and then 30 min as the patient tolerated. Intensity was adjusted to 60%– 70% of ageadjusted maximum heart rates Duration: Twice a week for 8 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— SF36 (physical component summary) Followup at 0 and 8 weeks Pain intensity and functionality were improved in RT Panton et al.(2009) 27 women with FM Mean age: 48 years Exp: 15– 10 Ctrl: 12– 11 7/11 Exp: RT included chest press, leg extension, leg curl, leg press, arm curl, seated dip, overhead press, seated row, abdominal crunch and low back extension. Initially, 1 set of 12 (50% 1RM), and then 1RM (100%) Ctrl: the same RT program combined with chiropractic treatment Duration: twice a week for 16 weeks (1) Functionality— CSPFP (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 16 weeks There were similar improvements in severity of the disease and functionality in both groups Kayo et al.(2011) 90 women with FM Mean age: 46 years Exp: 30– 22 Ctrl 1: 30– 23 Ctrl 2: 30– 23 6/11 Exp: RT included 11 free active exercises using free and body weight. 3 set of 10 reps, and them 3 set of 15 reps Ctrl 1: aerobic exercise (walking). Initially, 25– 30 min (40%– 50% HHR), and them 50 min (60%– 70%) Ctrl 2: no intervention Duration: three times a week for 16 weeks (1) Pain intensity— VAS (0– 10) and SF26 (bodily pain) (2) Functionality— FIQ (0– 100) and SF36 (physical function) (3) Severity of the disease— FIQ (0– 100) Followup at 0, 8, 16 and 28 weeks (7 months) All variables improved in both intervention group. Gavi et al.(2014) 80 women with FM Mean age: 46 years Exp: 40– 35 Ctrl: 40– 31 7/11 Exp: RT included leg press, leg extension, hip flexion, fly, triceps extension, shoulder flexion, abduction and extension, leg curl, calf, pulldown, biceps flexion. Three sets of 12 (45% 1RM) Ctrl: A flexibility exercise program of the major muscles, but exercises were not specified Duration: Twice a week for 16 weeks (1) Pain intensity— VAS (0– 10) (2) Functionality— SF36 (physical component summary) (3) Severity of the disease— FIQ (0– 100) Followup at 0 and 16 weeks Both groups showed improvements in the pain intensity, functionality and severity of the disease, and there was no significant difference observed between the groups Larsson et al.(2015) 130 women with FM Mean age: 51 years Exp: 67– 48 Ctrl: 63– 43 6/11 Exp: The main muscle groups were worked, but exercises were not specified. Intensity increased progressively Ctrl: Relaxation therapy approximately 25 min Duration: Twice a week for 15 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— SF36 (physical component summary) (3) Severity of the disease— FIQ (0– 100) Followup at 0 and 15 weeks, and 13 and 18 months Pain intensity, functionality and severity of the disease improved significantly in RT (Continues) 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 26 | RODRÍGUEZDOMÍNGUEZ et al. standardized mean difference and its standard error (Higgins & Green,2006). The quantitative synthesis of the results was performed by one of the other authors. In each metaanalysis, a subgroup division was made considering the different comparison groups. In this way, the studies were grouped by different intervention modalities compared to the experimental group. Where studies provided several postintervention measurements, we selected the measurement closest to 3 months (12 weeks). This criterion was established because most studies performed this intervention period. According to Cochrane, ‘thresholds for the interpretation of the I2 statistic can be misleading since the importance of inconsistency depends on several factors. A rough guide to interpretation in the context of metaanalyses of randomized trials is as follows: 0% to 40%: might not be important; 30% to 60%: may represent moderate heterogeneity; 50% to 90%: may represent substantial heterogeneity; 75% to 100%: considerable heterogeneity’ (Deeks et al.,2022). In all cases, the appropriate forest plot is depicted. Review Manager version 5.4.1 software was used for the statistical analysis. Where possible, publication bias was estimated using the Begg and Egger test and the funnel plot. Moreover, a sensitivity analysis was carried out (where possible) to estimate the degree of influence of each article included in each metaanalysis on the results of that metaanalysis. The ‘Epidat 3.1.’ program was used to analyse publication bias and sensitivity analysis. Where it was not possible to combine the study results in the metaanalysis, narrative and descriptive summaries Study Sample PEDro score Intervention Outcome measure and followup Reported results Assumpção et al.(2018) 37 women with FM Mean age: 52 years Exp: 19– 16 Ctrl 1: 18– 14 Ctrl 2: 16– 14 6/11 Exp: RT included exercise for triceps surae, quadriceps, hip adductors and abductors, hip flexors, elbow flexors and extensors, pectoralis major and rhomboids. 1 set of 8 reps Ctrl 1: stretching programbased postural reeducation method included triceps surae, gluteus, ischiotibial, paravertebral, latissimus dorsi, hip adductor and pectoralis muscles. The position was held for 30 seconds Ctrl 2: No intervention Duration: Twice a week for 12 weeks (1) Pain intensity (2) Functionality— FIQ (physical function) and SF36 (physical function) Severity of the disease— FIQ (0– 100) Followup at 0 and 12 weeks • Pain intensity and functionality improved in both intervention group, but stretching group was higher than RT group • Severity of the disease decreased in RT Glasgow et al.(2017) 26 women with FM Mean age: 52 years Exp: 14– 13 Ctrl: 12– 12 5/11 Exp: RT included chest press, leg extension, leg curl and seated row. Three sets of 8– 12 (50%– 60% 1RM) Ctrl: No intervention Duration: Twice a week for 8 weeks (1) Severity of the disease— FIQ (0– 100) Followup at 0 and 8 weeks Severity of the disease was significantly reduced in the RT Ernberg et al.(2018) 125 women with FM Mean age: 49 years Ctrl: 67– 49 Exp: 58– 43 6/11 Exp: RT were not specified but focusing on the lower body. Each session included warm up (10 min bicycling) Ctrl: Relaxation therapy Duration: Twice a week for 15 weeks (1) Pain intensity— VAS (0– 100) (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 15 weeks Pain intensity and severity of the disease was improved in RT Silva et al.(2019) 60 women with FM Mean age: 47 years Exp: 30– 28 Ctrl: 30– 27 8/11 Exp: RT included exercises for biceps brachial, triceps, pectoralis, trapezius, knee extensors and flexors, and hip abductors. Three sets of 12%– 60% 1RM, and then 70%– 80% Ctrl: Relaxation therapy (sophrology technique). The patients remained lying on comfortable mats with relaxing music playing in the background in a room with pleasant temperature. Each session lasted 40 min Duration: Twice a week for 12 weeks (1) Pain intensity— VAS (0– 10) (2) Functionality— SF36 (functional capacity) (3) Severity of disease— FIQ Followup at 0, 4, 8 and 12 weeks • Pain intensity showed no improvement at 4 and 8 weeks, but showed significant improvement at 12 weeks in RT • Functionality and severity of disease improved significantly in RT Jablochkova et al.(2019) 75 women with FM Mean age: 49 years Exp: 41– 41 Ctrl: 34– 34 7/11 Exp: RT were not specified but focusing on the lower body. Each session included warm up (10 min) Ctrl: Relaxation therapy contained mental exercises (25 min). All sessions ended with stretching Duration: Twice a week for 15 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— SF36 (physical component summary) (3) Severity of the disease— FIQ (0– 100) Followup at 0 and 15 weeks • Pain intensity was significantly decreased in RT • Functionality and severity of the disease improved in RT Arakaki et al.(2021) 60 women with FM Mean age: 47 years Exp: 30– 28 Ctrl: 30– 26 9/11 Exp: RT using a swiss ball (65 cm) and dumbbells. Three sets of 12 to 60% 1RM with 1– 2 min rest between exercises Ctrl: flexibility exercise was realized. The same muscles trained. Three sets of 30 s stretching Duration: Three times a week for 12 weeks (1) Pain intensity— VAS (0– 100) and SF36 (bodily pain) (2) Functionality— SF36 (functional capacity) (3) Severity of the disease— FIQ (0– 100) Followup at 0, 6 and 12 weeks All variables improved significantly in both groups, but in RT group was higher than control group Abbreviations: 1RM, repetition maximum; AE, aerobic exercise; CSPFP, ContinuousScale Physical Functional Performance; Ctrl, control group; Exp, experimental group; FIQ, Fibromyalgia Impact Questionnaire; FM, Fibromyalgia; HAQ, Stanford Health Assessment Questionnaire; MPI, Multidimensional Pain Inventory; SF36, shortform health survey; ST, strength training; VAS, visual analogue scale. 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 27 RODRÍGUEZDOMÍNGUEZ et al. were completed, and a qualitative synthesis of these was carried out. The strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) using the GRADE Pro/ Guideline Development Tool. This tool covers risk of bias, inconsistency, indirectness, imprecision and publication bias (Balshem et al.,2011). 2.7 | Clinical relevance Clinical relevance was determined by the minimal clinically important difference (MCID), defined as the minimal difference in scores of an outcome measure that is perceived by patients as beneficial or harmful (King,2014). The Philadelphia Panel developed the standard of 15% relative benefit based on extensive input by rheumatology and biostatistics experts (Albright et al.,2001). This is consistent with Bennett 2009, who indicated that a MCID in the FIQ total score (severity of disease) was at least a 14% reduction (Bennett et al.,2009). We evaluated the clinical relevance of the effects in the main outcomes by calculating the relative difference in change from a pooled baseline in the intervention group as compared with the change from a pooled baseline in the control or comparison group. This method was used by Cochrane 2013 to calculate the percentage change in people with fibromyalgia (Busch et al.,2013). To obtain the mean difference, independent pairwise metaanalyses were performed for each tool per variable. Study Sample PEDro score Intervention Outcome measure and followup Reported results Assumpção et al.(2018) 37 women with FM Mean age: 52 years Exp: 19– 16 Ctrl 1: 18– 14 Ctrl 2: 16– 14 6/11 Exp: RT included exercise for triceps surae, quadriceps, hip adductors and abductors, hip flexors, elbow flexors and extensors, pectoralis major and rhomboids. 1 set of 8 reps Ctrl 1: stretching programbased postural reeducation method included triceps surae, gluteus, ischiotibial, paravertebral, latissimus dorsi, hip adductor and pectoralis muscles. The position was held for 30 seconds Ctrl 2: No intervention Duration: Twice a week for 12 weeks (1) Pain intensity (2) Functionality— FIQ (physical function) and SF36 (physical function) Severity of the disease— FIQ (0– 100) Followup at 0 and 12 weeks • Pain intensity and functionality improved in both intervention group, but stretching group was higher than RT group • Severity of the disease decreased in RT Glasgow et al.(2017) 26 women with FM Mean age: 52 years Exp: 14– 13 Ctrl: 12– 12 5/11 Exp: RT included chest press, leg extension, leg curl and seated row. Three sets of 8– 12 (50%– 60% 1RM) Ctrl: No intervention Duration: Twice a week for 8 weeks (1) Severity of the disease— FIQ (0– 100) Followup at 0 and 8 weeks Severity of the disease was significantly reduced in the RT Ernberg et al.(2018) 125 women with FM Mean age: 49 years Ctrl: 67– 49 Exp: 58– 43 6/11 Exp: RT were not specified but focusing on the lower body. Each session included warm up (10 min bicycling) Ctrl: Relaxation therapy Duration: Twice a week for 15 weeks (1) Pain intensity— VAS (0– 100) (2) Severity of the disease— FIQ (0– 100) Followup at 0 and 15 weeks Pain intensity and severity of the disease was improved in RT Silva et al.(2019) 60 women with FM Mean age: 47 years Exp: 30– 28 Ctrl: 30– 27 8/11 Exp: RT included exercises for biceps brachial, triceps, pectoralis, trapezius, knee extensors and flexors, and hip abductors. Three sets of 12%– 60% 1RM, and then 70%– 80% Ctrl: Relaxation therapy (sophrology technique). The patients remained lying on comfortable mats with relaxing music playing in the background in a room with pleasant temperature. Each session lasted 40 min Duration: Twice a week for 12 weeks (1) Pain intensity— VAS (0– 10) (2) Functionality— SF36 (functional capacity) (3) Severity of disease— FIQ Followup at 0, 4, 8 and 12 weeks • Pain intensity showed no improvement at 4 and 8 weeks, but showed significant improvement at 12 weeks in RT • Functionality and severity of disease improved significantly in RT Jablochkova et al.(2019) 75 women with FM Mean age: 49 years Exp: 41– 41 Ctrl: 34– 34 7/11 Exp: RT were not specified but focusing on the lower body. Each session included warm up (10 min) Ctrl: Relaxation therapy contained mental exercises (25 min). All sessions ended with stretching Duration: Twice a week for 15 weeks (1) Pain intensity— VAS (0– 100) (2) Functionality— SF36 (physical component summary) (3) Severity of the disease— FIQ (0– 100) Followup at 0 and 15 weeks • Pain intensity was significantly decreased in RT • Functionality and severity of the disease improved in RT Arakaki et al.(2021) 60 women with FM Mean age: 47 years Exp: 30– 28 Ctrl: 30– 26 9/11 Exp: RT using a swiss ball (65 cm) and dumbbells. Three sets of 12 to 60% 1RM with 1– 2 min rest between exercises Ctrl: flexibility exercise was realized. The same muscles trained. Three sets of 30 s stretching Duration: Three times a week for 12 weeks (1) Pain intensity— VAS (0– 100) and SF36 (bodily pain) (2) Functionality— SF36 (functional capacity) (3) Severity of the disease— FIQ (0– 100) Followup at 0, 6 and 12 weeks All variables improved significantly in both groups, but in RT group was higher than control group Abbreviations: 1RM, repetition maximum; AE, aerobic exercise; CSPFP, ContinuousScale Physical Functional Performance; Ctrl, control group; Exp, experimental group; FIQ, Fibromyalgia Impact Questionnaire; FM, Fibromyalgia; HAQ, Stanford Health Assessment Questionnaire; MPI, Multidimensional Pain Inventory; SF36, shortform health survey; ST, strength training; VAS, visual analogue scale. 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 28 | RODRÍGUEZDOMÍNGUEZ et al. 3 | RESULTS Figure1 describes the study selection process carried out. All (14) articles were included in the qualitative synthesis. The degree of agreement reached between the two reviewers in the selection of the articles was excellent, with Cohen's Kappa coefficient showing a value of 0.89 (standard Error 0.08; CI 0.73 to 1.00; with p < 0.001). 3.1 | Characteristics of the studies All of the studies were published in English between 2001 and 2021. The sample size varied from 21 to 130 patients, with a mean of 55 participants. The total number of patients evaluated was 894 participants. The mean age was approximately 48 years (range = 39– 60 years). The sociodemographic and clinical characteristics of the participants in each study, the sample size and the number of participants assigned to each group are shown in Table1. 3.2 | Intervention characteristics The duration of the interventions was between 8 and 21 weeks, with the most common being 12 weeks (four studies). Most of the interventions were performed with a training frequency twice a week. Only two studies (Arakaki et al.,2021; Kayo et al.,2011) prescribed the exercise program three times a week. All workouts included 10 min of warmup, 50 min of RT and 10 min of relaxation at the end, which consisted of stretching exercises. During FIGURE 1 PRISMA flowchart of study selection. Records identified from: PubMed (n = 931); Cochrane (n = 59); WoS (n = 47); CINAHL (n = 22); Scopus (n = 90); PEDro (n = 75) Dialnet (n = 4) Registers (n = 1.228) Records removed before screening: Duplicate records removed (n = 48) Records marked as ineligible by automation tools (n = 0) Records removed for other reasons (n = 0) Records screened (n = 1.180) Records excluded (n = 1.141) Reports excluded: Not apply ST in patients with fibromyalgia (n = 1.140) Included men (n = 1) Reports sought for retrieval (n = 39) Reports not retrieved (n = 0) Reports assessed for eligibility (n = 39) Reports excluded: Not only resistance training (n = 8) Not evaluated study variables (n = 6) Not randomized (n = 10) Duplicate results (n= 1) Studies included in review (n = 14) Identification of studies via databases and registers Identification Screening Included Studies included in metaanalysis (n = 14) 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 29 RODRÍGUEZDOMÍNGUEZ et al. training, patients were instructed to take 1 min of recovery between each set. The RT programs used in the studies included a range of 4– 12 exercises, but several authors did not report the program used. Although most focused on the main muscle groups, two of the studies focused on working in the lower body (Ernberg et al., 2018; Jablochkova et al.,2019). In terms of intensity, several studies began with 40%– 60% of the one repetition maximum (1RM). However, others used increased repetitions to increase intensity. In this way, the number of repetitions was inversely proportional to the intensity. While some started in sets of four to five repetitions and increased to 12 repetitions (Jones et al.,2002), others started in sets of more volume (15– 20 repetitions) and at the end of treatment increased the intensity to perform sets of 5– 10 repetitions (Valkeinen et al.,2004). It should be noted that the program designed by Larsson et al.(2015) was replicated by two other studies (Ernberg et al.,2018; Jablochkova et al.,2019). This program included seven exercises (leg press, leg extension, leg curl, biceps curl, hand grip strength, core stability exercise and heel raise) and consisted of 15 weeks of progressive RT, starting with 15– 20 repetitions at 40% of 1RM, progressing to 5– 8 repetitions at 80% of 1RM. The last 5 weeks included explosive execution of rapid heel raises and explosive knee extension. 3.3 | Quality assessment Overall, the quality of the included trials was good, with 14 of the 15 included studies scoring >5 on the PEDro scale. Only one study (Glasgow et al.,2017) had a score of ≤5, and two had an ‘excellent’ (Arakaki et al.,2021; Kingsley et al.,2005; TableS2). 3.4 | Treatment results Forest plots represent the effect size calculated for each study by results, as well as the overall effect size obtained for the study results at each time interval. The forest plots also indicate whether the effects obtained in the studies favour the control group or the intervention group. FIGURE 2 Effectiveness of resistance training for pain intensity in women with fibromyalgia (forest plot of the metaanalysis). 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. 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European Journal of Pain, 28, 21–36. https://doi.org/10.1002/ejp.2161 15322149, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejp.2161 by Universidad De Sevilla, Wiley Online Library on [10/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License