title: 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.
abstract: 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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrial.gov Identifier: NCT01682980.
authors.affiliation: Norwegian Research Center for Active Rehabilitation (NAR), Department of Orthopedics, Oslo University Hospital, Kirkeveien 166, 0407 Oslo, Norway. britt.e.oiestad@nimi.no.
authors.forename: Britt Elin
authors.initials: BE
authors.lastname: Øiestad
authors.forename: Nina
authors.initials: N
authors.lastname: Østerås
authors.forename: Richard
authors.initials: R
authors.lastname: Frobell
authors.forename: Margreth
authors.initials: M
authors.lastname: Grotle
authors.forename: Helga
authors.initials: H
authors.lastname: Brøgger
authors.forename: May Arna
authors.initials: MA
authors.lastname: Risberg
mesh_terms: D000368:Aged; D018771:Arthralgia / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D001642:Bicycling / Q000191:economics; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000503:physiopathology; D003362:Cost-Benefit Analysis; D005081:Exercise Therapy / Q000191:economics / Q000379:methods*; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009664:Norway; D020370:Osteoarthritis, Knee / Q000150:complications / Q000175:diagnosis / Q000191:economics / Q000503:physiopathology / Q000628:therapy*; D010147:Pain Measurement; D011788:Quality of Life; D011859:Radiography; D012107:Research Design; D055070:Resistance Training / Q000191:economics; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
references.citation: Arthritis Rheum. 2003 Jun 15;49(3):342-8
references.pmid: 12794789
references.citation: Osteoarthritis Cartilage. 2010 Apr;18(4):476-99
references.pmid: 20170770
references.citation: Osteoarthritis Cartilage. 1999 Mar;7(2):216-21
references.pmid: 10222220
references.citation: Cochrane Database Syst Rev. 2008 Oct 08;(4):CD004376
references.pmid: 18843657
references.citation: Osteoarthritis Cartilage. 2006 Jan;14(1):71-6
references.pmid: 16188465
references.citation: Osteoarthritis Cartilage. 2004 May;12(5):389-99
references.pmid: 15094138
references.citation: J Rheumatol. 1988 Dec;15(12):1833-40
references.pmid: 3068365
references.citation: Phys Ther. 2008 Apr;88(4):427-36
references.pmid: 18218827
references.citation: Arthritis Care Res (Hoboken). 2012 Jan;64(1):46-53
references.pmid: 22012877
references.citation: J Orthop Sports Phys Ther. 1998 Aug;28(2):88-96
references.pmid: 9699158
references.citation: Ann Intern Med. 2000 Nov 7;133(9):726-37
references.pmid: 11074906
references.citation: BMC Musculoskelet Disord. 2013 Jul 05;14:201
references.pmid: 23826721
references.citation: Rheumatol Int. 2012 Apr;32(4):1009-14
references.pmid: 21246372
references.citation: J Orthop Sports Phys Ther. 2012 Dec;42(12):985-95
references.pmid: 22951360
references.citation: Ann Rheum Dis. 2011 Nov;70(11):1884-6
references.pmid: 21908453
references.citation: BMJ. 2008 Mar 1;336(7642):502-3
references.pmid: 18310005
references.citation: Osteoarthritis Cartilage. 2013 Jan;21(1):69-76
references.pmid: 23059757
references.citation: Arthritis Res Ther. 2010;12(4):R126
references.pmid: 20594330
references.citation: Br J Sports Med. 2011 Jun;45(7):583-8
references.pmid: 20647299
references.citation: Arch Phys Med Rehabil. 2013 Mar;94(3):419-25
references.pmid: 23131526
references.citation: Arthritis Care Res (Hoboken). 2011 Nov;63(11):1535-42
references.pmid: 21954070
references.citation: Med Clin North Am. 2009 Jan;93(1):161-77, xii
references.pmid: 19059027
references.citation: Osteoarthritis Cartilage. 2011 May;19(5):550-6
references.pmid: 21396469
references.citation: BMC Musculoskelet Disord. 2011 Dec 05;12:276
references.pmid: 22141334
references.citation: Value Health. 2012 Jan;15(1):1-12
references.pmid: 22264966
references.citation: Ann N Y Acad Sci. 2010 Nov;1211:37-50
references.pmid: 21062294
references.citation: Osteoarthritis Cartilage. 2011 May;19(5):606-10
references.pmid: 21396466
references.citation: Arthritis Rheum. 1986 Aug;29(8):1039-49
references.pmid: 3741515
references.citation: Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74
references.pmid: 22563589
references.citation: Aust N Z J Psychiatry. 2005 Jul;39(7):583-90
references.pmid: 15996139
references.citation: Ann Rheum Dis. 1957 Dec;16(4):494-502
references.pmid: 13498604
references.citation: Osteoarthritis Cartilage. 2012 Jan;20(1):13-21
references.pmid: 22044841
references.citation: Ann Rheum Dis. 2013 Jul;72(7):1125-35
references.pmid: 23595142
references.citation: Arthritis Rheum. 1989 Jan;32(1):37-44
references.pmid: 2912463
references.citation: Rheumatology (Oxford). 1999 Sep;38(9):807-13
references.pmid: 10515639
references.citation: Rheum Dis Clin North Am. 2008 Aug;34(3):531-59
references.pmid: 18687271
references.citation: BMC Musculoskelet Disord. 2008 Apr 21;9:55
references.pmid: 18426591
references.citation: Rheumatology (Oxford). 2005 Jan;44(1):67-73
references.pmid: 15353613
references.citation: Osteoarthritis Cartilage. 2013 Jan;21(1):16-21
references.pmid: 23194896
references.citation: Med Sci Sports Exerc. 2009 Mar;41(3):687-708
references.pmid: 19204579
references.citation: Eur Radiol. 2004 Sep;14(9):1568-73
references.pmid: 15150666
references.citation: Arthritis Care Res (Hoboken). 2010 Jan 15;62(1):45-53
references.pmid: 20191490
references.citation: Orthop Clin North Am. 2012 Apr;43(2):187-99, v
references.pmid: 22480468
references.citation: Ann Intern Med. 2012 Nov 6;157(9):632-44
references.pmid: 23128863
references.citation: Ann Rheum Dis. 2005 Apr;64(4):544-8
references.pmid: 15769914
references.citation: Knee Surg Sports Traumatol Arthrosc. 2010 Nov;18(11):1617-23
references.pmid: 20405106
references.citation: Ann Intern Med. 2013 Feb 5;158(3):200-7
references.pmid: 23295957
references.citation: Arthritis Rheum. 2006 Apr 15;55(2):306-13
references.pmid: 16583430
references.citation: J Magn Reson Imaging. 2012 Jan;35(1):147-55
references.pmid: 21990043
references.citation: J Sci Med Sport. 2011 Jan;14(1):4-9
references.pmid: 20851051
references.citation: J Rheumatol. 2009 Jun;36(6):1109-17
references.pmid: 19447940
references.citation: Health Qual Life Outcomes. 2003 Nov 03;1:64
references.pmid: 14613558
references.citation: BMC Public Health. 2012 Dec 12;12:1073
references.pmid: 23234575
references.citation: Rheum Dis Clin North Am. 2008 Aug;34(3):731-54
references.pmid: 18687280
references.citation: J Rheumatol. 2006 Apr;33(4):744-56
references.pmid: 16583478
references.citation: Med Phys. 2009 Sep;36(9):4059-67
references.pmid: 19810478
references.citation: J Orthop Sports Phys Ther. 2010 Nov;40(11):705-21
references.pmid: 20710097
references.citation: Clin Physiol Funct Imaging. 2008 Mar;28(2):113-9
references.pmid: 18070123
references.citation: Arthritis Rheum. 2008 Oct 15;59(10):1488-94
references.pmid: 18821647