THE SIGNIFICANCE AND EFFICACY OF RESISTANCE EXERCISE IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) – A CLINICAL AND MOLECULAR PERSPECTIVE
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6480Keywords:
Rheumatoid Arthritis, Resistance Training, Mechanotransduction, Myokines, Sarcopenic Obesity, FITT-VP FrameworkAbstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by progressive joint destruction and immunometabolic complications, notably rheumatoid cachexia. This review article investigates the significance and efficacy of resistance exercise in mitigating myopenia, sarcopenic obesity, and systemic inflammation in RA patients. The objective is to elucidate the underlying molecular mechanotransduction pathways, the role of myokines, and the clinical outcomes of progressive resistance training (PRT). A comprehensive review of the current literature, including recent randomized controlled trials and meta-analyses, was conducted to evaluate clinical and physiological effects. The findings indicate that PRT effectively counteracts muscle atrophy by activating the mTORC1 pathway and exerts potent anti-inflammatory effects via the release of muscle-derived interleukin-6 (IL-6). Furthermore, PRT demonstrates synergistic potential with modern biological and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). Clinically, properly dosed PRT improves functional capacity, reduces cardiovascular risk, and alleviates patient-reported outcomes such as fatigue and sleep disruption, without exacerbating synovial inflammation or radiographic progression in stable RA. We conclude that structured resistance training is a crucial, evidence-based non-pharmacological therapy for RA — warranting equal consideration alongside standard aerobic exercises — and provide structured dosing guidelines based on the FITT-VP framework.
References
Akira, S., & Kishimoto, T. (1996). Role of interleukin-6 in macrophage function. Current Opinion in Hematology, 3(1), 87–93. https://doi.org/10.1097/00062752-199603010-00013
Bačenková, D., Trebuňová, M., Demeterová, J., & Živčák, J. (2023). Human chondrocytes, metabolism of articular cartilage, and strategies for application to tissue engineering. International Journal of Molecular Sciences, 24(23), 17096. https://doi.org/10.3390/ijms242317096
Baillet, A., Vaillant, M., Guinot, M., Juvin, R., & Gaudin, P. (2012). Efficacy of resistance exercises in rheumatoid arthritis: meta-analysis of randomized controlled trials. Rheumatology (Oxford), 51(3), 519–527. https://doi.org/10.1093/rheumatology/ker330
Baker, J. F., Giles, J. T., Weber, D., George, M. D., Leonard, M. B., Zemel, B. S., Long, J., & Katz, P. (2022). Sarcopenic obesity in rheumatoid arthritis: prevalence and impact on physical functioning. Rheumatology (Oxford), 61(6), 2285–2294. https://doi.org/10.1093/rheumatology/keab710
Banerjee, D., & Mani, A. (2025). Obesity's systemic impact: exploring molecular and physiological links to diabetes, cardiovascular disease, and heart failure. Frontiers in Endocrinology, 16, 1681766. https://doi.org/10.3389/fendo.2025.1681766
Barry, S., Sheng, E., & Baker, J. F. (2025). Metabolic consequences of rheumatoid arthritis. Arthritis Care & Research, 77, 1167–1174. https://doi.org/10.1002/acr.25537
Bennett, J. L., Hollingsworth, K. G., Pratt, A. G., Degnan, A. E. A., Gorman, G. S., Feeney, C., Naamane, N., Nsengimana, J., Sayer, A. A., Anderson, A. E., & Isaacs, J. D. (2026). Skeletal muscle effects of Janus kinase inhibition in rheumatoid arthritis (RAMUS): a single-arm, experimental medicine study. The Lancet Rheumatology, 8(1), e42–e52. https://doi.org/10.1016/S2665-9913(25)00184-5
Bonewald, L. F. (2006). Mechanosensation and transduction in osteocytes. Bonekey Osteovision, 3(10), 7–15. https://doi.org/10.1138/20060233
Burr, D. B., Robling, A. G., & Turner, C. H. (2002). Effects of biomechanical stress on bones in animals. Bone, 30(5), 781–786. https://doi.org/10.1016/s8756-3282(02)00707-x
Cao, Y., Zhou, J., Quan, H., Li, W., Li, T., & Wang, L. (2025). Resistance training alleviates muscle atrophy and muscle dysfunction by reducing inflammation and regulating compromised autophagy in aged skeletal muscle. Frontiers in Immunology, 16, 1597222. https://doi.org/10.3389/fimmu.2025.1597222
Carroll, S. F., Buckley, C. T., & Kelly, D. J. (2014). Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad. Journal of Biomechanics, 47(9), 2115–2121. https://doi.org/10.1016/j.jbiomech.2013.12.006
Casanova-Vallve, N., Constantin-Teodosiu, D., Filer, A., Hardy, R. S., Greenhaff, P. L., & Chapman, V. (2020). Skeletal muscle dysregulation in rheumatoid arthritis: Metabolic and molecular markers in a rodent model and patients. PLoS One, 15(7), e0235702. https://doi.org/10.1371/journal.pone.0235702
Choy, E. H., & Panayi, G. S. (2001). Cytokine pathways and joint inflammation in rheumatoid arthritis. The New England Journal of Medicine, 344(12), 907–916. https://doi.org/10.1056/NEJM200103223441207
Clemente-Suárez, V. J., Redondo-Flórez, L., Beltrán-Velasco, A. I., Martín-Rodríguez, A., Martínez-Guardado, I., Navarro-Jiménez, E., Laborde-Cárdenas, C. C., & Tornero-Aguilera, J. F. (2023). The role of adipokines in health and disease. Biomedicines, 11(5), 1290. https://doi.org/10.3390/biomedicines11051290
Cong, C., Wang, Y., Liu, J., & Jin, C. (2026). Role of the PI3K/AKT signaling pathway in regulating gene expression in rheumatoid arthritis (Review). Molecular Medicine Reports, 34(1), 205. https://doi.org/10.3892/mmr.2026.13915
Cooney, J. K., Law, R. J., Matschke, V., Lemmey, A. B., Moore, J. P., Ahmad, Y., Jones, J. G., Maddison, P., & Thom, J. M. (2011). Benefits of exercise in rheumatoid arthritis. Journal of Aging Research, 2011, 681640. https://doi.org/10.4061/2011/681640
Cruz-Jentoft, A. J., Bahat, G., Bauer, J., Boirie, Y., Bruyère, O., Cederholm, T., Cooper, C., Landi, F., Rolland, Y., Sayer, A. A., Schneider, S. M., Sieber, C. C., Topinkova, E., Vandewoude, M., Visser, M., Zamboni, M., & Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). (2019). Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing, 48(1), 16–31. https://doi.org/10.1093/ageing/afy169
de Jong, Z., Munneke, M., Zwinderman, A. H., Kroon, H. M., Jansen, A., Ronday, K. H., van Schaardenburg, D., Dijkmans, B. A., Van den Ende, C. H., Breedveld, F. C., Vliet Vlieland, T. P., & Hazes, J. M. (2003). Is a long-term high-intensity exercise program effective and safe in patients with rheumatoid arthritis? Results of a randomized controlled trial. Arthritis & Rheumatism, 48(9), 2415–2424. https://doi.org/10.1002/art.11216
de Jong, Z., Munneke, M., Zwinderman, A. H., Kroon, H. M., Ronday, K. H., Lems, W. F., Dijkmans, B. A., Breedveld, F. C., Vliet Vlieland, T. P., Hazes, J. M., & Huizinga, T. W. (2004). Long term high intensity exercise and damage of small joints in rheumatoid arthritis. Annals of the Rheumatic Diseases, 63(11), 1399–1405. https://doi.org/10.1136/ard.2003.015826
den Broeder, N., Bolhuis, T. E., van Herwaarden, N., Bergstra, S. A., Bouman, C. A. M., van den Hoogen, F. H. J., Verhoef, L. M., den Broeder, A. A., & van der Maas, A. (2025). Effect of using the Simple Erosion Narrowing Score or Sharp/van der Heijde score on the power of rheumatoid arthritis clinical trials to detect differences in radiographic progression. Rheumatology (Oxford), 64(3), 1464–1468. https://doi.org/10.1093/rheumatology/keae328
Dey, M., Parodis, I., & Nikiphorou, E. (2021). Fatigue in systemic lupus erythematosus and rheumatoid arthritis: A comparison of mechanisms, measures and management. Journal of Clinical Medicine, 10(16), 3566. https://doi.org/10.3390/jcm10163566
Dures, E., Almeida, C., Caesley, J., Peterson, A., Amour, A., & Hewlett, S. (2020). Physical activity and psychological well-being in patients with rheumatoid arthritis. Musculoskeletal Care, 18(2), 150–159. https://doi.org/10.1002/msc.1447
England, B. R., Smith, B. J., Baker, N. A., Barton, J. L., Oatis, C. A., Guyatt, G., ... & Treadwell, J. R. (2023). 2022 American College of Rheumatology guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis. Arthritis Care & Research, 75(8), 1603–1615. https://doi.org/10.1002/acr.25117
Gabay, C. (2006). Interleukin-6 and chronic inflammation. Arthritis Research & Therapy, 8 Suppl 2(Suppl 2), S3. https://doi.org/10.1186/ar1917
Gillick, J. L., Wainwright, J., & Das, K. (2015). Rheumatoid arthritis and the cervical spine: A review on the role of surgery. International Journal of Rheumatology, 2015, 252456. https://doi.org/10.1155/2015/252456
Haack, M., Simpson, N., Sethna, N., Kaur, S., & Mullington, J. (2020). Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 45(1), 205–216. https://doi.org/10.1038/s41386-019-0439-z
Hein, T. R., Peterson, L., Bartikoski, B. J., Portes, J., Espírito Santo, R. C., & Xavier, R. M. (2022). The effect of disease-modifying anti-rheumatic drugs on skeletal muscle mass in rheumatoid arthritis patients: a systematic review with meta-analysis. Arthritis Research & Therapy, 24(1), 171. https://doi.org/10.1186/s13075-022-02858-y
Hemat Jouy, S., Mohan, S., Scichilone, G., Mostafa, A., & Mahmoud, A. M. (2024). Adipokines in the crosstalk between adipose tissues and other organs: Implications in cardiometabolic diseases. Biomedicines, 12(9), 2129. https://doi.org/10.3390/biomedicines12092129
Hornberger, T. A. (2011). Mechanotransduction and the regulation of mTORC1 signaling in skeletal muscle. The International Journal of Biochemistry & Cell Biology, 43(9), 1267–1276. https://doi.org/10.1016/j.biocel.2011.05.007
Hurkmans, E., van der Giesen, F. J., Vliet Vlieland, T. P., Schoones, J., & Van den Ende, E. C. (2009). Dynamic exercise programs (aerobic capacity and/or muscle strength training) in patients with rheumatoid arthritis. Cochrane Database of Systematic Reviews, (4), CD006853. https://doi.org/10.1002/14651858.CD006853.pub2
Jahid, M., Khan, K. U., Rehan-Ul-Haq, & Ahmed, R. S. (2023). Overview of rheumatoid arthritis and scientific understanding of the disease. Mediterranean Journal of Rheumatology, 34(3), 284–291. https://doi.org/10.31138/mjr.20230801.oo
Jiang, X., Yu, L., Yan, Y., Zhou, S., & Zheng, Q. (2025). The effect of exercise on fatigue in rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. International Journal of Osteopathic Medicine, 58, 100794. https://doi.org/10.1016/j.ijosm.2025.100794
Jin, H., Wang, G., Lu, Q., Rawlins, J., Chen, J., Kashyap, S., Charlesworth, O., Xu, D., Dai, L., Zhu, S., & Xu, J. (2025). Pathophysiology of myopenia in rheumatoid arthritis. Bone Research, 13(1), 64. https://doi.org/10.1038/s41413-025-00438-9
Kareem, R., Botleroo, R. A., Bhandari, R., Ogeyingbo, O. D., Ahmed, R., Gyawali, M., Venkatesan, N., & Elshaikh, A. O. (2021). The impact of rheumatoid arthritis on bone loss: Links to osteoporosis and osteopenia. Cureus, 13(8), e17519. https://doi.org/10.7759/cureus.17519
Kenkre, J. S., & Bassett, J. (2018). The bone remodelling cycle. Annals of Clinical Biochemistry, 55(3), 308–327. https://doi.org/10.1177/0004563218759371
Kim, H. R., Kim, K. W., Kim, B. M., Jung, H. G., Cho, M. L., & Lee, S. H. (2014). Reciprocal activation of CD4+ T cells and synovial fibroblasts by stromal cell-derived factor 1 promotes RANKL expression and osteoclastogenesis in rheumatoid arthritis. Arthritis & Rheumatology, 66(3), 538–548. https://doi.org/10.1002/art.38286
Lemmey, A. B., Marcora, S. M., Chester, K., Wilson, S., Casanova, F., & Maddison, P. J. (2009). Effects of high-intensity resistance training in patients with rheumatoid arthritis: a randomized controlled trial. Arthritis & Rheumatism, 61(12), 1726–1734. https://doi.org/10.1002/art.24891
Lemmey, A. B., Williams, J. E., Marcora, S. M., Jones, J., & Maddison, P. J. (2012). Tight control of disease activity fails to improve body composition or muscle strength in early rheumatoid arthritis. Rheumatology (Oxford), 51(12), 2235–2243. https://doi.org/10.1093/rheumatology/kes223
Lourenzi, F. M., Jones, A., Pereira, D. F., Santos, J. H. C. A. D., Furtado, R. N. V., & Natour, J. (2017). Effectiveness of an overall progressive resistance strength program for improving the functional capacity of patients with rheumatoid arthritis: a randomized controlled trial. Clinical Rehabilitation, 31(11), 1482–1491. https://doi.org/10.1177/0269215517698732
Metsios, G. S., Stavropoulos-Kalinoglou, A., Veldhuijzen van Zanten, J. J., Nightingale, P., Sandoo, A., Dimitroulas, T., Kitas, G. D., & Koutedakis, Y. (2014). Individualised exercise improves endothelial function in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases, 73(4), 748–751. https://doi.org/10.1136/annrheumdis-2013-203291
Meyer, E. G., Buckley, C. T., Steward, A. J., & Kelly, D. J. (2011). The effect of cyclic hydrostatic pressure on the functional development of cartilaginous tissues engineered using bone marrow derived mesenchymal stem cells. Journal of the Mechanical Behavior of Biomedical Materials, 4(7), 1257–1265. https://doi.org/10.1016/j.jmbbm.2011.04.012
Munneke, M., de Jong, Z., Zwinderman, A. H., Ronday, H. K., van den Ende, C. H., Vliet Vlieland, T. P., Hazes, J. M., & CROON study group. (2005). Effect of a high-intensity weight-bearing exercise program on radiologic damage progression of the large joints in subgroups of patients with rheumatoid arthritis. Arthritis & Rheumatism, 53(3), 410–417. https://doi.org/10.1002/art.21175
Ogawa, K., Sanada, K., Machida, S., Okutsu, M., & Suzuki, K. (2010). Resistance exercise training-induced muscle hypertrophy was associated with reduction of inflammatory markers in elderly women. Mediators of Inflammation, 2010, 171023. https://doi.org/10.1155/2010/171023
Ollewagen, T., Myburgh, K. H., van de Vyver, M., & Smith, C. (2021). Rheumatoid cachexia: the underappreciated role of myoblast, macrophage and fibroblast interplay in the skeletal muscle niche. Journal of Biomedical Science, 28(1), 15. https://doi.org/10.1186/s12929-021-00714-w
Oranchuk, D. J., Storey, A. G., Nelson, A. R., & Cronin, J. B. (2019). Isometric training and long-term adaptations: Effects of muscle length, intensity, and intent: A systematic review. Scandinavian journal of medicine & science in sports, 29(4), 484–503. https://doi.org/10.1111/sms.13375
Pedersen, B. K., & Fischer, C. P. (2007). Physiological roles of muscle-derived interleukin-6 in response to exercise. Current Opinion in Clinical Nutrition & Metabolic Care, 10(3), 265–271. https://doi.org/10.1097/MCO.0b013e3280ebb5b3
Pedersen, B. K., Steensberg, A., & Schjerling, P. (2001). Muscle-derived interleukin-6: possible biological effects. The Journal of Physiology, 536(Pt 2), 329–337. https://doi.org/10.1111/j.1469-7793.2001.0329c.xd
Petersen, A. M., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of Applied Physiology, 98(4), 1154–1162. https://doi.org/10.1152/japplphysiol.00164.2004
Pineda-Juárez, J. A., Lozada-Mellado, M., Hinojosa-Azaola, A., García-Morales, J. M., Ogata-Medel, M., Llorente, L., Alcocer-Varela, J., Orea-Tejeda, A., Martín-Nares, E., & Castillo-Martínez, L. (2022). Changes in hand grip strength and body weight after a dynamic exercise program and Mediterranean diet in women with rheumatoid arthritis: a randomized clinical trial. Physiotherapy Theory and Practice, 38(4), 504–512. https://doi.org/10.1080/09593985.2020.1777605
Rausch Osthoff, A. K., Vlieland, T. P. M. V., Ferreira, R. J. O., Amarnani, R., Battista, S., Orlinov, D., ... & Niedermann, K. (2026). EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis: 2025 update. Annals of the Rheumatic Diseases, 85(6), 1026–1038. https://doi.org/10.1016/j.ard.2026.03.006
Schett, G., & Gravallese, E. (2012). Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nature Reviews Rheumatology, 8(11), 656–664. https://doi.org/10.1038/nrrheum.2012.153
Shrager, J. B., Randle, R., Lee, M., Ahmed, S. S., Trope, W., Lui, N., ... & Tang, H. (2024). JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle. Life Science Alliance, 7(11), e202402885. https://doi.org/10.26508/lsa.202402885
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M. S., Lüthy, R., ... & Boyle, W. J. (1997). Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell, 89(2), 309–319. https://doi.org/10.1016/s0092-8674(00)80209-3
Smolen, J. S., Aletaha, D., Barton, A., Burmester, G. R., Emery, P., Firestein, G. S., Kavanaugh, A., McInnes, I. B., Solomon, D. H., Strand, V., & Yamamoto, K. (2018). Rheumatoid arthritis. Nature Reviews Disease Primers, 4, 18001. https://doi.org/10.1038/nrdp.2018.1
Steensberg, A., Fischer, C. P., Keller, C., Møller, K., & Pedersen, B. K. (2003). IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. American Journal of Physiology. Endocrinology and Metabolism, 285(2), E433–E437. https://doi.org/10.1152/ajpendo.00074.2003
Sveaas, S. H., Smedslund, G., Hagen, K. B., & Dagfinrud, H. (2017). Effect of cardiorespiratory and strength exercises on disease activity in patients with inflammatory rheumatic diseases: a systematic review and meta-analysis. British Journal of Sports Medicine, 51(14), 1065–1072. https://doi.org/10.1136/bjsports-2016-097149
Tan, Z., Jiang, Y., Candow, D. G., Castagna, C., Wang, X., & Zheng, H. (2026). Optimizing prescription of resistance training for body composition, muscle strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis. European Review of Aging and Physical Activity, 23(1), 8. https://doi.org/10.1186/s11556-025-00399-2
van der Heijde D. (2000). How to read radiographs according to the Sharp/van der Heijde method. The Journal of rheumatology, 27(1), 261–263.
Velloso, C. P. (2008). Regulation of muscle mass by growth hormone and IGF-I. British Journal of Pharmacology, 154(3), 557–568. https://doi.org/10.1038/bjp.2008.153
Wada, E., Tanihata, J., Iwamura, A., Takeda, S., Hayashi, Y. K., & Matsuda, R. (2017). Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice. Skeletal Muscle, 7(1), 23. https://doi.org/10.1186/s13395-017-0140-z
Wen, Z., & Chai, Y. (2021). Effectiveness of resistance exercises in the treatment of rheumatoid arthritis: A meta-analysis. Medicine (Baltimore), 100(13), e25019. https://doi.org/10.1097/MD.0000000000025019
Wu, M. L., Ma, J. K., Tsui, K., Hoens, A. M., & Li, L. C. (2022). Tailoring strength training prescriptions for people with rheumatoid arthritis: A scoping review. American Journal of Lifestyle Medicine, 18(2), 200–215. https://doi.org/10.1177/15598276221125415
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Wiktoria Napiórkowska, Aleksandra Izabela Masłowska, Zuzanna Chmielewska, Oliwia Lenkiewicz, Agata Kotłowska, Julia Lenkiewicz, Anna Gwóźdź-Broczkowska, Gabriela Luba, Marcin Trzciński
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
