The preventive and therapeutic role of physical activity in knee osteoarthritis

Submitted: 20 October 2021
Accepted: 18 February 2022
Published: 3 May 2022
Abstract Views: 5472
PDF: 2406
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

The aim of this narrative review is to discuss the results of studies investigating the role of physical activity in knee osteoarthritis (OA). We also formulated two evidence-based exercise programs that could be prescribed to patients with symptomatic knee OA or after joint replacement. The PubMed and Google Scholar databases were searched for articles related to knee OA and physical activity. A total of 86 papers written in English and published from 1957 to 2021 were selected. Adapted physical activity, even at high intensity, does not appear to trigger or exacerbate knee OA; on the contrary, it may prevent obesity or lower limb muscle weakness, both of which are considered predisposing factors for the disease. In patients already diagnosed with knee OA, scientific evidence suggests that both land-based and aquatic activities combining aerobics, strength, and endurance programs are safe and effective. Physical interventions tailored to the patient may also accelerate recovery time after knee arthroplasty. Knee OA is a painful and disabling rheumatic disease that is very common in the elderly population. Pharmacotherapy has a modest effect in controlling disease progression, possibly due to the still limited understanding of OA pathogenesis. Non-pharmacologic interventions, including dietary and lifestyle changes and physical activity, may be more effective and safer than drugs in preventing or treating knee OA.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019; 393: 30417-9. DOI: https://doi.org/10.1016/S0140-6736(19)30417-9
Wallace IJ, Worthington S, Felson DT, et al. Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci. 2017; 114: 9332-6. DOI: https://doi.org/10.1073/pnas.1703856114
Kohn MD, Sassoon AA, Fernando ND. IN BRIEF Classifications in Brief Kellgren-Lawrence Classification of Osteoarthritis. Clin Orthop Relat Res. 2016; 474: 1886-93. DOI: https://doi.org/10.1007/s11999-016-4732-4
Firestein GS. Kelley’s Textbook of Rheumatology, Eighth Edition. Vol. 8, Kelley’s Textbook of Rheumatology; 2009.
Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: Structure, function and cartilage bone crosstalk. Vol. 12, Nature Reviews Rheumatology. Nature Publishing Group; 2016. p. 632-44. DOI: https://doi.org/10.1038/nrrheum.2016.148
Deveza LA, Loeser RF. Is osteoarthritis one disease or a collection of many? Rheumatology. 2018; 57: iv34-iv42. DOI: https://doi.org/10.1093/rheumatology/kex417
Bierma-Zeinstra SMA, Verhagen AP. Osteoarthritis subpopulations and implications for clinical trial design. Arthrit Res Therapy. 2011; 13. DOI: https://doi.org/10.1186/ar3299
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957; 16: 494-502. DOI: https://doi.org/10.1136/ard.16.4.494
Dell’Isola A, Allan R, Smith SL, et al. Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature. BMC Musculoskelet Disord. 2016; 17: 425. DOI: https://doi.org/10.1186/s12891-016-1286-2
Felson DT. Identifying different osteoarthritis phenotypes through epidemiology. Osteoarthr Cartil. 2010; 18: 601-4. DOI: https://doi.org/10.1016/j.joca.2010.01.007
Dell’isola A, Steultjens M. Classification of patients with knee osteoarthritis in clinical phenotypes: Data from the osteoarthritis initiative. PLoS One. 2018; 13: e0191045. DOI: https://doi.org/10.1371/journal.pone.0191045
Leblanc DR, Schneider M, Angele P, et al. The effect of estrogen on tendon and ligament metabolism and function. J Steroid Biochem Mol Biol. 2017; 172: 106-16. DOI: https://doi.org/10.1016/j.jsbmb.2017.06.008
Wang T, He C. Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine Growth Factor Rev. 2018; 44: 38-50. DOI: https://doi.org/10.1016/j.cytogfr.2018.10.002
Corti MC, Rigon C. Epidemiology of osteoarthritis: prevalence, risk factors and functional impact. Aging Clin Exp Res. 2003; 15: 359-63. DOI: https://doi.org/10.1007/BF03327356
Lee Y, Lee S-H, Lim SM, Baek SH, Ha I-H. Mental health and quality of life of patients with osteoarthritis pain: The sixth Korea National Health and Nutrition Examination Survey (2013–2015). PLoS One. 2020; 15: e0242077-undefined. DOI: https://doi.org/10.1371/journal.pone.0242077
da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017; 390: e21-33. DOI: https://doi.org/10.1016/S0140-6736(17)31744-0
Kan H, Chan P, Chiu K, et al. Non-surgical treatment of knee osteoarthritis. Hong Kong Med J. 2019; 127-33. DOI: https://doi.org/10.12809/hkmj187600
Wang ZY, Shi SY, Li SJ, et al. Efficacy and safety of duloxetine on osteoarthritis knee pain: a meta-analysis of randomized controlled trials. Pain Med. 2015; 16: 1373-85. DOI: https://doi.org/10.1111/pme.12800
Altman R, Hackel J, Niazi F, et al. Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review. Semin Arthritis Rheum. 2018; 48: 168-75. DOI: https://doi.org/10.1016/j.semarthrit.2018.01.009
Davatchi F, Abdollahi BS, Mohyeddin M, et al. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011; 14: 211-5. DOI: https://doi.org/10.1111/j.1756-185X.2011.01599.x
Chapman K, Valdes AM. Genetic factors in OA pathogenesis. Bone. 2012; 51: 258-64. DOI: https://doi.org/10.1016/j.bone.2011.11.026
Roos EM, Arden NK. Strategies for the prevention of knee osteoarthritis. Nat Rev Rheumatol. 2016; 12: 92-101. DOI: https://doi.org/10.1038/nrrheum.2015.135
Neogi T, Zhang Y. Osteoarthritis prevention. Curr Opin Rheumatol. 2011; 23: 185-91. DOI: https://doi.org/10.1097/BOR.0b013e32834307eb
Sadeghi A, Rad ZA, Sajedi B, et al. Effect of weight losing on the clinical status improvement of patients with knee osteoarthritis. Reumatol Clínica. 2019; 15: 73-6. DOI: https://doi.org/10.1016/j.reuma.2017.06.016
Runhaar J, Deroisy R, van Middelkoop M, et al. The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study. Semin Arthritis Rheum. 2016; 45: S42-8. DOI: https://doi.org/10.1016/j.semarthrit.2015.11.001
Harber VJ, Sutton JR. Endorphins and Exercise. Sport Med. 1984; 1: 154-71. DOI: https://doi.org/10.2165/00007256-198401020-00004
Semanik PA, Chang RW, Dunlop DD. Aerobic activity in prevention and symptom control of osteoarthritis. PM&R. 2012; 4: S37-44. DOI: https://doi.org/10.1016/j.pmrj.2012.02.015
Driban JB, Hootman JM, Sitler MR, et al. Is participation in certain sports associated with knee osteoarthritis? A Systematic Review. J Athl Train. 2017; 52: 497-506. DOI: https://doi.org/10.4085/1062-6050-50.2.08
Golightly YM, Marshall SW, Callahan LF, Guskiewicz K. Early-onset arthritis in retired national football league players. J Phys Act Heal. 2009; 6: 638-43. DOI: https://doi.org/10.1123/jpah.6.5.638
Chang AH, Lee J, Chmiel JS, et al. Association of Long-term Strenuous Physical Activity and Extensive Sitting With Incident Radiographic Knee Osteoarthritis. JAMA Netw Open. 2020; 3: e204049-undefined. DOI: https://doi.org/10.1001/jamanetworkopen.2020.4049
Smith JK. Exercise as an adjuvant to cartilage regeneration therapy. Int J Mol Sci. 2020; 21: 9471-undefined. DOI: https://doi.org/10.3390/ijms21249471
Castrogiovanni P, Di Rosa M, Ravalli S, et al. Moderate physical activity as a prevention method for knee osteoarthritis and the role of synoviocytes as biological key. Int J Mol Sci. 2019; 20: 511-undefined. DOI: https://doi.org/10.3390/ijms20030511
Bricca A, Wirth W, Juhl CB, et al. Moderate physical activity and prevention of cartilage loss in people with knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Care Res (Hoboken). 2019; 71: 218-26. DOI: https://doi.org/10.1002/acr.23791
Rabe KG, Matsuse H, Jackson A, Segal NA. Evaluation of the combined application of neuromuscular electrical stimulation and volitional contractions on thigh muscle strength, knee pain, and physical performance in women at risk for knee osteoarthritis: a randomized controlled trial. PM&R. 2018; 10: 1301-10. DOI: https://doi.org/10.1016/j.pmrj.2018.05.014
Karamanidis K, Oberländer KD, Niehoff A, et al. Effect of exercise-induced enhancement of the leg-extensor muscle-tendon unit capacities on ambulatory mechanics and knee osteoarthritis markers in the elderly. PLoS One. 2014; 9: e99330-undefined. DOI: https://doi.org/10.1371/journal.pone.0099330
Song R, Roberts BL, Lee E-O, et al. A randomized study of the effects of T’ai Chi on muscle strength, bone mineral density, and fear of falling in women with osteoarthritis. J Altern Complement Med. 2010; 16: 227-33.
Rausch Osthoff A-K, Niedermann K, Braun J, et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis. 2018; 77: 1251-60. DOI: https://doi.org/10.1136/annrheumdis-2018-213585
Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020; 72: 220-33. DOI: https://doi.org/10.1002/art.41142
Dong R, Wu Y, Xu S, et al. Is aquatic exercise more effective than land-based exercise for knee osteoarthritis? Medicine (Baltimore). 2018; 97: e13823-undefined. DOI: https://doi.org/10.1097/MD.0000000000013823
Bartels EM, Juhl CB, Christensen R, et al. Aquatic exercise for the treatment of knee and hip osteoarthritis. Cochrane Database Syst Rev. 2016 Mar 23. DOI: https://doi.org/10.1002/14651858.CD005523.pub3
Lau MC, Lam JK, Siu E, et al. Physiotherapist-designed aquatic exercise programme for community-dwelling elders with osteoarthritis of the knee: a Hong Kong pilot study. Hong Kong Med J. 2013; 20: 16-23. DOI: https://doi.org/10.12809/hkmj133931
Dias JM, Cisneros L, Dias R, et al. Hydrotherapy improves pain and function in older women with knee osteoarthritis: a randomized controlled trial. Brazilian J Phys Ther. 2017; 21: 449-56. DOI: https://doi.org/10.1016/j.bjpt.2017.06.012
Taglietti M, Facci LM, Trelha CS, et al. Effectiveness of aquatic exercises compared to patient-education on health status in individuals with knee osteoarthritis: a randomized controlled trial. Clin Rehabil. 2018; 32: 766-76. DOI: https://doi.org/10.1177/0269215517754240
Munukka M, Waller B, Rantalainen T, et al. Efficacy of progressive aquatic resistance training for tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis: a randomised controlled trial. Osteoarthr Cartil. 2016; 24: 1708-17. DOI: https://doi.org/10.1016/j.joca.2016.05.007
Bekkers JEJ, Bartels LW, Benink RJ, et al. Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) can be effectively applied for longitudinal cohort evaluation of articular cartilage regeneration. Osteoarthr Cartil. 2013; 21: 943-9. DOI: https://doi.org/10.1016/j.joca.2013.03.017
Waller B, Munukka M, Rantalainen T, et al. Effects of high intensity resistance aquatic training on body composition and walking speed in women with mild knee osteoarthritis: a 4-month RCT with 12-month follow-up. Osteoarthr Cartil. 2017; 25: 1238-46. DOI: https://doi.org/10.1016/j.joca.2017.02.800
Cheung C, Wyman JF, Bronas U, et al. Managing knee osteoarthritis with yoga or aerobic/strengthening exercise programs in older adults: a pilot randomized controlled trial. Rheumatol Int. 2017; 37: 389-98. DOI: https://doi.org/10.1007/s00296-016-3620-2
Helmark IC, Mikkelsen UR, Børglum J, et al. Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Res Ther. 2010; 12: R126-undefined. DOI: https://doi.org/10.1186/ar3064
Messier SP, Loeser RF, Miller GD, et al. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: The arthritis, diet, and activity promotion trial. Arthritis Rheum. 2004; 50: 1501-10. DOI: https://doi.org/10.1002/art.20256
Barry E, Galvin R, Keogh C, et al. Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis. BMC Geriatr. 2014; 14: 14-undefined. DOI: https://doi.org/10.1186/1471-2318-14-14
Lin D-H, Lin C-HJ, Lin Y-F, Jan M-H. Efficacy of 2 non-weight-bearing interventions, proprioception training versus strength training, for patients with knee osteoarthritis: a randomized clinical trial. J Orthop Sport Phys Ther. 2009; 39: 450-7. DOI: https://doi.org/10.2519/jospt.2009.2923
Hall M, Dobson F, Van Ginckel A, et al. Comparative effectiveness of exercise programs for psychological well-being in knee osteoarthritis: A systematic review and network meta-analysis. Semin Arthritis Rheum. 2021; 51: 1023-32. DOI: https://doi.org/10.1016/j.semarthrit.2021.07.007
Hall M, Hinman RS, Wrigley TV, et al. Knee extensor strength gains mediate symptom improvement in knee osteoarthritis: secondary analysis of a randomised controlled trial. Osteoarthr Cartil. 2018; 26: 495-500. DOI: https://doi.org/10.1016/j.joca.2018.01.018
Liao C De, Liao YH, Liou TH, et al. Effects of protein-rich nutritional composition supplementation on sarcopenia indices and physical activity during resistance exercise training in older women with knee osteoarthritis. Nutrients. 2021; 13(8). DOI: https://doi.org/10.3390/nu13082487
Sayers SP, Gibson K, Cook CR. Effect of high-speed power training on muscle performance, function, and pain in older adults with knee osteoarthritis: A pilot investigation. Arthritis Care Res (Hoboken). 2012; 64: 46-53. DOI: https://doi.org/10.1002/acr.20675
Sayers SP, Gibson K. High-speed power training in older adults. J Strength Cond Res. 2014; 28: 616-21. DOI: https://doi.org/10.1519/JSC.0b013e3182a361b8
Van Ginckel A, Hall M, Dobson F, Calders P. Effects of long-term exercise therapy on knee joint structure in people with knee osteoarthritis: A systematic review and meta-analysis. Vol. 48, Seminars in Arthritis and Rheumatism. W.B. Saunders; 2019. p. 941-9. DOI: https://doi.org/10.1016/j.semarthrit.2018.10.014
Simic M, Harmer AR, Agaliotis M, et al. Clinical risk factors associated with radiographic osteoarthritis progression among people with knee pain: a longitudinal study. Arthritis Res Ther. 2021; 23(1). DOI: https://doi.org/10.1186/s13075-021-02540-9
Zou L, Sasaki J, Wei G-X, et al. Effects of mind-body exercises (Tai Chi/Yoga) on heart rate variability parameters and perceived stress: a systematic review with meta-analysis of randomized controlled trials. J Clin Med. 2018; 7: 404-. DOI: https://doi.org/10.3390/jcm7110404
Wang C, Schmid CH, Hibberd PL, et al. Tai Chi is effective in treating knee osteoarthritis: A randomized controlled trial. Arthritis Rheum. 2009; 61: 1545-53. DOI: https://doi.org/10.1002/art.24832
Song R, Roberts BL, Lee E-O, et al. A randomized study of the effects of Tai Chi on muscle strength, bone mineral density, and fear of falling in women with osteoarthritis. J Altern Complement Med. 2010; 16: 227-33. DOI: https://doi.org/10.1089/acm.2009.0165
You Y, Liu J, Tang M, et al. Effects of Tai Chi exercise on improving walking function and posture control in elderly patients with knee osteoarthritis: A systematic review and meta-analysis. Medicine (Baltimore). 2021; 100: e25655. DOI: https://doi.org/10.1097/MD.0000000000025655
Hu L, Wang Y, Liu X, et al. Tai Chi exercise can ameliorate physical and mental health of patients with knee osteoarthritis: systematic review and meta-analysis. Clin Rehabil. 2021; 35: 64-79. DOI: https://doi.org/10.1177/0269215520954343
Lauche R, Hunter DJ, Adams J, Cramer H. Yoga for osteoarthritis: a systematic review and meta-analysis. Curr Rheumatol Rep. 2019; 21. DOI: https://doi.org/10.1007/s11926-019-0846-5
Brouwer RW, Huizinga MR, Duivenvoorden T, et al. Osteotomy for treating knee osteoarthritis. Cochrane Database Syst Rev. 2014; 2014(12). DOI: https://doi.org/10.1002/14651858.CD004019.pub4
Wang B, Sun H, Fu Z, et al. Application of unicompartmental knee arthroplasty in the treatment of knee osteoarthritis. Arthroplasty. 2021; 3: 12-undefined. DOI: https://doi.org/10.1186/s42836-020-00065-1
Torres-Claramunt R, Gil-González S, Hinarejos-Gómez P, et al. Resultados funcionales y de calidad de vida tras una artroplastía total de rodilla al año y cinco años de seguimiento [Functional and quality of life results after a total knee replacement per year and five years of follow-up]. Acta Ortop Mex. 2020; 34: 211-4. DOI: https://doi.org/10.35366/97553
Yuan A, Cai D, Wang K. [Analysis of factors relating to clinical outcomes after total knee replacement]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007; 21: 235-9.
Bade MJ, Struessel T, Dayton M, et al. Early high-intensity versus low-intensity rehabilitation after total knee arthroplasty: a randomized controlled trial. Arthritis Care Res. 2017; 69: 1360-8. DOI: https://doi.org/10.1002/acr.23139
Jørgensen PB, Bogh SB, Kierkegaard S, et al. The efficacy of early initiated, supervised, progressive resistance training compared to unsupervised, home-based exercise after unicompartmental knee arthroplasty: A single-blinded randomized controlled trial. Clin Rehabil. 2017; 31: 61-70. DOI: https://doi.org/10.1177/0269215516640035
Jakobsen TL, Kehlet H, Husted H, et al. Early progressive strength training to enhance recovery after fast-track total knee arthroplasty: A randomized controlled trial. Arthritis Care Res. 2014; 66: 1856-66. DOI: https://doi.org/10.1002/acr.22405
Husby VS, Foss OA, Husby OS, Winther SB. Randomized controlled trial of maximal strength training vs. standard rehabilitation following total knee arthroplasty. Eur J Phys Rehabil Med. 2018; 54: 371-9. DOI: https://doi.org/10.23736/S1973-9087.17.04712-8
Hsu WH, Hsu W Bin, Shen WJ, et al. Twenty-four-week hospital-based progressive resistance training on functional recovery in female patients post total knee arthroplasty. Knee. 2019; 26: 729-36. DOI: https://doi.org/10.1016/j.knee.2019.02.008
Hamilton DF, Beard DJ, Barker KL, et al. Targeting rehabilitation to improve outcomes after total knee arthroplasty in patients at risk of poor outcomes: Randomised controlled trial. BMJ. 2020; 371. DOI: https://doi.org/10.1136/bmj.m3576
Moutzouri M, Coutts F, Gliatis J, et al. Early initiation of home-based sensori-motor training improves muscle strength, activation and size in patients after knee replacement: A secondary analysis of a controlled clinical trial. BMC Musculoskelet Disord. 2019; 20(1). DOI: https://doi.org/10.1186/s12891-019-2575-3
Bedekar N, Shyam A, Sancheti P, et al. Comparative study of conventional therapy and additional yogasanas for knee rehabilitation after total knee arthroplasty. Int J Yoga. 2012; 5: 118-22. DOI: https://doi.org/10.4103/0973-6131.98226
Lee H-G, An J, Lee B-H. The effect of progressive dynamic balance training on physical function, the ability to balance and quality of life among elderly women who underwent a total knee arthroplasty: a double-blind randomized control trial. Int J Environ Res Public Health. 2021; 18: 2513-. DOI: https://doi.org/10.3390/ijerph18052513
Valtonen A, Pöyhönen T, Sipilä S, Heinonen A. Effects of aquatic resistance training on mobility limitation and lower-limb impairments after knee replacement. Arch Phys Med Rehabil. 2010; 91: 833-9. DOI: https://doi.org/10.1016/j.apmr.2010.03.002
Valtonen A, Pöyhönen T, Sipilä S, Heinonen A. Maintenance of aquatic training-induced benefits on mobility and lower-extremity muscles among persons with unilateral knee replacement. Arch Phys Med Rehabil. 2011; 92: 1944-50. DOI: https://doi.org/10.1016/j.apmr.2011.07.191
Harmer AR, Naylor JM, Crosbie J, Russell T. Land-based versus water-based rehabilitation following total knee replacement: A randomized, single-blind trial. Arthritis Rheum. 2009; 61: 184-91. DOI: https://doi.org/10.1002/art.24420
Grässel S, Muschter D. Recent advances in the treatment of osteoarthritis. Vol. 9, F1000Research. F1000 Research Ltd; 2020. DOI: https://doi.org/10.12688/f1000research.22115.1
Toyoda E, Maehara M, Watanabe M, Sato M. Candidates for intra-articular administration therapeutics and therapies of osteoarthritis. Vol. 22, International Journal of Molecular Sciences. MDPI; 2021. DOI: https://doi.org/10.3390/ijms22073594
Veenhof C, Van Den Ende CHM, Dekker J, et al. Which patients with osteoarthritis of hip and/or knee benefit most from behavioral graded activity? Int J Behav Med. 2007; 14: 86-91. DOI: https://doi.org/10.1007/BF03004173
Lim BW, Hinman RS, Wrigley TV, et al. Does knee malalignment mediate the effects of quadriceps strengthening on knee adduction moment, pain, and function in medial knee osteoarthritis? A randomized controlled trial. Arthritis Care Res. 2008; 59: 943-51. DOI: https://doi.org/10.1002/art.23823
Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. 2019; 27: 1578-89. DOI: https://doi.org/10.1016/j.joca.2019.06.011
Wang TJ, Lee SC, Liang SY, et al. Comparing the efficacy of aquatic exercises and land-based exercises for patients with knee osteoarthritis. J Clin Nurs. 2011; 20: 2609-22. DOI: https://doi.org/10.1111/j.1365-2702.2010.03675.x

How to Cite

Restuccia, R., Ruggieri, D., Magaudda, L., & Talotta, R. (2022). The preventive and therapeutic role of physical activity in knee osteoarthritis. Reumatismo, 74(1). https://doi.org/10.4081/reumatismo.2022.1466