Efficacy of strength and aerobic exercise on patient-reported outcomes and structural changes in patients with knee osteoarthritis: study protocol for a randomized controlled trial

BMC Musculoskeletal Disorders

May Arna Risberg⁶  Helga Brøgger⁵  Margreth Grotle²  Richard Frobell⁴  Nina Østerås¹  Britt Elin Øiestad³ 

[1] National Resource Center for Rehabilitation in Rheumatology, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway;Oslo University College, Oslo, Norway;Norwegian Research Center for Active Rehabilitation (NAR), Department of Orthopedics, Oslo University Hospital, Kirkeveien 166, 0407 Oslo, Norway;Department of Orthopaedics, Lund University Hospital, Lund, Sweden;Department of Radiology, Oslo University Hospital Ullevaal, Oslo, Norway;Department of Sport Medicine, Norwegian School of Sport Sciences, Oslo, Norway

关键词: Cost-effectiveness;    Articular cartilage;    Exercise therapy;    Osteoarthritis;    Knee;   

Others  :  1129769
DOI  :  10.1186/1471-2474-14-266

 received in 2013-07-29, accepted in 2013-09-11,  发布年份 2013

【 摘 要 】

Background

Despite an extensive literature on treatment interventions for patients with knee osteoarthritis, studies comparing the efficacy of different exercise interventions and living the life as usual on quality of life, cartilage quality and cost-effectiveness are lacking. The aim of the present study is to compare the efficacy of two different exercise programs compared to a control group in individuals with established radiographic and symptomatic knee osteoarthritis on self-reported knee-related quality of life, knee pain, physical function, and cartilage quality.

Methods/Design

A three-armed randomized controlled trial involving two exercise interventions and a control group of individuals doing as they usually do is described. The patients will have mild to moderate radiographic osteoarthritis according to the Kellgren and Lawrence classification (grade 2–3), and fulfill the American College of Rheumatology clinical criteria, be aged between 45 and 65 years, and have no other serious physical or mental illnesses. The patients will be randomly allocated to a strength exercise group; a cycling group, or a control group. The primary outcome is the Knee injury and Osteoarthritis Outcome Score knee-related quality of life subscale. Secondary outcomes include all five Knee Injury and Osteoarthritis Outcome Score subscales, morphological evaluation of cartilage including focal thickness, subchondral bone marrow edema, proteoglycan content and collagen degradation (measured using magnetic resonance imaging clinical sequences, T2 mapping and T1ρ), specific serum biomarkers, isokinetic muscle strength, maximal oxygen uptake, quality of life (EuroQol 5D), and self-efficacy (Arthritis Self-Efficacy Scale). A sample size calculation on the primary outcome showed that 207 individuals, 69 in each group, is needed to detect a clinically relevant difference of 10 points with 80% power and a significance level of 5%. Assessments will be conducted at baseline, 14 weeks, 1 year and 2 years post-randomization. The interventions will be a 14 weeks exercise program.

Discussion

Although exercise therapy has been found to be effective in knee osteoarthritis, the knowledge of the underlying mechanisms for why exercise works is lacking. This study will contribute with knowledge on the efficacy of strength exercise versus cycling on patient-reported outcomes, cartilage quality and cost-effectiveness.

Trial registration

Clinicaltrial.gov Identifier: NCT01682980.

【 授权许可】

   
2013 Øiestad et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Conaghan PG, Dickson J, Grant RL: Care and management of osteoarthritis in adults: summary of NICE guidance. BMJ 2008, 336:502-503.
• [2]Bennell KL, Hinman RS: A review of the clinical evidence for exercise in osteoarthritis of the hip and knee. J Sci Med Sport 2011, 14:4-9.
• [3]Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al.: OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010, 18:476-499.
• [4]Fransen M, McConnell S: Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev 2008, 8(4):CD004376.
• [5]Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al.: American college of rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken ) 2012, 64:455-474.
• [6]Fernandes L, Hagen KB, Bijlsma JW, Andreassen O, Christensen P, Conaghan PG, et al.: EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis 2013, 72(7):1125-1135.
• [7]vos-Comby L, Cronan T, Roesch SC: Do exercise and self-management interventions benefit patients with osteoarthritis of the knee? A metaanalytic review. J Rheumatol 2006, 33:744-756.
• [8]Roddy E, Zhang W, Doherty M, Arden NK, Barlow J, Birrell F, et al.: Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee–the MOVE consensus. Rheumatology (Oxford) 2005, 44:67-73.
• [9]Roper JA, Bressel E, Tillman MD: Acute aquatic treadmill exercise improves gait and pain in people with knee osteoarthritis. Arch Phys Med Rehabil 2012, 94(3):419-425.
• [10]Salacinski AJ, Krohn K, Lewis SF, Holland ML, Ireland K, Marchetti G: The effects of group cycling on gait and pain-related disability in individuals with mild-to-moderate knee osteoarthritis: a randomized controlled trial. J Orthop Sports Phys Ther 2012, 42:985-995.
• [11]Brosseau L, Wells GA, Kenny GP, Reid R, Maetzel A, Tugwell P, et al.: The implementation of a community-based aerobic walking program for mild to moderate knee osteoarthritis: a knowledge translation randomized controlled trial: part II: clinical outcomes. BMC Public Health 2012, 12:1073.
• [12]Wang SY, Olson-Kellogg B, Shamliyan TA, Choi JY, Ramakrishnan R, Kane RL: Physical therapy interventions for knee pain secondary to osteoarthritis: a systematic review. Ann Intern Med 2012, 157:632-644.
• [13]McKnight PE, Kasle S, Going S, Villanueva I, Cornett M, Farr J, et al.: A comparison of strength training, self-management, and the combination for early osteoarthritis of the knee. Arthritis Care Res (Hoboken) 2010, 62:45-53.
• [14]Lange AK, Vanwanseele B, Fiatarone Singh MA: Strength training for treatment of osteoarthritis of the knee: a systematic review. Arthritis Rheum 2008, 59:1488-1494.
• [15]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.
• [16]Jan MH, Lin JJ, Liau JJ, Lin YF, Lin DH: Investigation of clinical effects of high- and low-resistance training for patients with knee osteoarthritis: a randomized controlled trial. Phys Ther 2008, 88:427-436.
• [17]Roddy E, Zhang W, Doherty M: Aerobic walking or strengthening exercise for osteoarthritis of the knee? A systematic review. Ann Rheum Dis 2005, 64:544-548.
• [18]Fransen M, McConnell S: Land-based exercise for osteoarthritis of the knee: a metaanalysis of randomized controlled trials. J Rheumatol 2009, 36:1109-1117.
• [19]Knoop J, van der LM, Thorstensson CA, Roorda LD, Lems WF, Knol DL, et al.: Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Care Res (Hoboken) 2011, 63:1535-1542.
• [20]Bennell KL, Hunt MA, Wrigley TV, Lim BW, Hinman RS: Role of muscle in the genesis and management of knee osteoarthritis. Rheum Dis Clin North Am 2008, 34:731-754.
• [21]Bennell KL, Hunt MA, Wrigley TV, Lim BW, Hinman RS: Muscle and exercise in the prevention and management of knee osteoarthritis: an internal medicine specialist’s guide. Med Clin North Am 2009, 93:161-177. xii
• [22]Bennell KL, Egerton T, Wrigley TV, Hodges PW, Hunt M, Roos EM, et al.: Comparison of neuromuscular and quadriceps strengthening exercise in the treatment of varus malaligned knees with medial knee osteoarthritis: a randomised controlled trial protocol. BMC Musculoskelet Disord 2011, 12:276.
• [23]Gahunia HK, Pritzker KP: Effect of exercise on articular cartilage. Orthop Clin North Am 2012, 43:187-199. v
• [24]Brandt KD, Dieppe P, Radin EL: Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am 2008, 34:531-559.
• [25]Berenbaum F: Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013, 21:16-21.
• [26]Helmark IC, Mikkelsen UR, Borglum J, Rothe A, Petersen MC, Andersen O, 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.
• [27]Helmark IC, Petersen MC, Christensen HE, Kjaer M, Langberg H: Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligomeric matrix protein. Rheumatol Int 2012, 32:1009-1014.
• [28]O’Kane JW, Hutchinson E, Atley LM, Eyre DR: Sport-related differences in biomarkers of bone resorption and cartilage degradation in endurance athletes. Osteoarthritis Cartilage 2006, 14:71-76.
• [29]Helmark IC, Mikkelsen UR, Krogsgaard MR, Belhage B, Petersen MC, Langberg H, et al.: Early osteoarthritis and microdialysis: a novel in vivo approach for measurements of biochemical markers in the perisynovium and intraarticularly. Knee Surg Sports Traumatol Arthrosc 2010, 18:1617-1623.
• [30]Pinto D, Robertson MC, Hansen P, Abbott JH: Cost-effectiveness of nonpharmacologic, nonsurgical interventions for hip and/or knee osteoarthritis: systematic review. Value Health 2012, 15:1-12.
• [31]Prasad AP, Nardo L, Schooler J, Joseph GB, Link TM: T(1)rho and T(2) relaxation times predict progression of knee osteoarthritis. Osteoarthritis Cartilage 2013, 21:69-76.
• [32]Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, et al.: SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Ann Intern Med 2013, 158:200-207.
• [33]Osteras N, Risberg MA, Kvien TK, Engebretsen L, Nordsletten L, Bruusgaard D, et al.: Hand, hip and knee osteoarthritis in a Norwegian population-based study–the MUST protocol. BMC Musculoskelet Disord 2013, 14:201.
• [34]Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al.: Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American rheumatism association. Arthritis Rheum 1986, 29:1039-1049.
• [35]Roos EM, Roos H, Ekdahl C, Lohmander LS, Beynnon BD: Knee injury and osteoarthritis outcome score (KOOS)-Development of a self-administered outcome measure. J Orthop Sports Phys 1998, 78:88-96.
• [36]Roos EM, Roos HP, Lohmander LS: WOMAC osteoarthritis index–additional dimensions for use in subjects with post-traumatic osteoarthritis of the knee. Western Ontario and MacMaster Universities. Osteoarthritis Cartilage 1999, 7:216-221.
• [37]Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW: Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988, 15:1833-1840.
• [38]Oiestad BE, Holm I, Engebretsen L, Risberg MA: The association between radiographic knee osteoarthritis and knee symptoms, function and quality of life 10–15 years after anterior cruciate ligament reconstruction. Br J Sports Med 2011, 45:583-588.
• [39]Kothari M, Guermazi A, von IG, Miaux Y, Sieffert M, Block JE, Kothari M, Guermazi A, Von IG, Miaux Y, Sieffert M, Block JE, et al.: Fixed-flexion radiography of the knee provides reproducible joint space width measurements in osteoarthritis. Eur Radiol 2004, 14:1568-1573.
• [40]Kellgren JH, Lawrence JS: Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957, 16:494-502.
• [41]Felson DT, Niu J, Guermazi A, Sack B, Aliabadi P: Defining radiographic incidence and progression of knee osteoarthritis: suggested modifications of the Kellgren and Lawrence scale. Ann Rheum Dis 2011, 70:1884-1886.
• [42]Reichmann WM, Maillefert JF, Hunter DJ, Katz JN, Conaghan PG, Losina E: Responsiveness to change and reliability of measurement of radiographic joint space width in osteoarthritis of the knee: a systematic review. Osteoarthritis Cartilage 2011, 19:550-556.
• [43]Conaghan PG, Hunter DJ, Maillefert JF, Reichmann WM, Losina E: Summary and recommendations of the OARSI FDA osteoarthritis assessment of structural change working group. Osteoarthritis Cartilage 2011, 19:606-610.
• [44]Fransen M, Edmonds J: Reliability and validity of the EuroQol in patients with osteoarthritis of the knee. Rheumatology (Oxford) 1999, 38:807-813.
• [45]Impellizzeri FM, Bizzini M, Rampinini E, Cereda F, Maffiuletti NA: Reliability of isokinetic strength imbalance ratios measured using the Cybex NORM dynamometer. Clin Physiol Funct Imaging 2008, 28:113-119.
• [46]Menashe L, Hirko K, Losina E, Kloppenburg M, Zhang W, Li L, et al.: The diagnostic performance of MRI in osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage 2012, 20:13-21.
• [47]Nishioka H, Hirose J, Nakamura E, Oniki Y, Takada K, Yamashita Y, et al.: T1rho and T2 mapping reveal the in vivo extracellular matrix of articular cartilage. J Magn Reson Imaging 2012, 35:147-155.
• [48]Carballido-Gamio J, Stahl R, Blumenkrantz G, Romero A, Majumdar S, Link TM: Spatial analysis of magnetic resonance T1rho and T2 relaxation times improves classification between subjects with and without osteoarthritis. Med Phys 2009, 36:4059-4067.
• [49]Felson DT, Lawrence RC, Hochberg MC, McAlindon T, Dieppe PA, Minor MA, et al.: Osteoarthritis: new insights. Part 2: treatment approaches. Ann Intern Med 2000, 133:726-737.
• [50]Brekke M, Hjortdahl P, Kvien TK: Changes in self-efficacy and health status over 5 years: a longitudinal observational study of 306 patients with rheumatoid arthritis. Arthritis Rheum 2003, 49:342-348.
• [51]Lorig K, Chastain RL, Ung E, Shoor S, Holman HR: Development and evaluation of a scale to measure perceived self-efficacy in people with arthritis. Arthritis Rheum 1989, 32:37-44.
• [52]Hinman RS, May RL, Crossley KM: Is there an alternative to the full-leg radiograph for determining knee joint alignment in osteoarthritis? Arthritis Rheum 2006, 55:306-313.
• [53]American College of Sports Medicine position stand: Progression models in resistance training for healthy adults. Med Sci Sports Exerc 2009, 41:687-708.
• [54]Pham T, van der HD, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al.: OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004, 12:389-399.
• [55]Eitzen I, Moksnes H, Snyder-Mackler L, Risberg MA: A progressive 5-week exercise therapy program leads to significant improvement in knee function early after anterior cruciate ligament injury. J Orthop Sports Phys Ther 2010, 40:705-721.
• [56]Sun HB: Mechanical loading, cartilage degradation, and arthritis. Ann N Y Acad Sci 2010, 1211:37-50.
• [57]Kapstad H, Hanestad BR, Langeland N, Rustoen T, Stavem K: Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery. BMC Musculoskelet Disord 2008, 9:55.
• [58]Roos EM, Lohmander LS: The Knee injury and osteoarthritis outcome score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes 2003, 1:64.
• [59]Hawthorne G, Elliott P: Imputing cross-sectional missing data: comparison of common techniques. Aust N Z J Psychiatry 2005, 39:583-590.