Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial | Geriatrics | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Lawrence  RC, Felson  DT, Helmick  CG,  et al; National Arthritis Data Workgroup.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States, II.  Arthritis Rheum. 2008;58(1):26-35.PubMedGoogle ScholarCrossref
Mapel  DW, Shainline  M, Paez  K, Gunter  M.  Hospital, pharmacy, and outpatient costs for osteoarthritis and chronic back pain.  J Rheumatol. 2004;31(3):573-583.PubMedGoogle Scholar
Losina  E, Paltiel  AD, Weinstein  AM,  et al.  Lifetime medical costs of knee osteoarthritis management in the United States: impact of extending indications for total knee arthroplasty.  Arthritis Care Res (Hoboken). 2015;67(2):203-215.PubMedGoogle ScholarCrossref
Berenbaum  F.  Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!).  Osteoarthritis Cartilage. 2013;21(1):16-21.PubMedGoogle ScholarCrossref
Hill  CL, Hunter  DJ, Niu  J,  et al.  Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis.  Ann Rheum Dis. 2007;66(12):1599-1603.PubMedGoogle ScholarCrossref
Roemer  FW, Guermazi  A, Felson  DT,  et al.  Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study.  Ann Rheum Dis. 2011;70(10):1804-1809.PubMedGoogle ScholarCrossref
Ayral  X, Pickering  EH, Woodworth  TG, Mackillop  N, Dougados  M.  Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis—results of a 1 year longitudinal arthroscopic study in 422 patients.  Osteoarthritis Cartilage. 2005;13(5):361-367.PubMedGoogle ScholarCrossref
Jüni  P, Hari  R, Rutjes  AWS,  et al.  Intra-articular corticosteroid for knee osteoarthritis.  Cochrane Database Syst Rev. 2015;(10):CD005328.PubMedGoogle Scholar
Hartmann  K, Koenen  M, Schauer  S,  et al.  Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy.  Physiol Rev. 2016;96(2):409-447.PubMedGoogle ScholarCrossref
Wada  J, Koshino  T, Morii  T, Sugimoto  K.  Natural course of osteoarthritis of the knee treated with or without intraarticular corticosteroid injections.  Bull Hosp Jt Dis. 1993;53(2):45-48.PubMedGoogle Scholar
Haddad  IK.  Temporomandibular joint osteoarthrosis: histopathological study of the effects of intra-articular injection of triamcinolone acetonide.  Saudi Med J. 2000;21(7):675-679.PubMedGoogle Scholar
Wernecke  C, Braun  HJ, Dragoo  JL.  The effect of intra-articular corticosteroids on articular cartilage: a systematic review.  Orthop J Sports Med. 2015;3(5):2325967115581163.PubMedGoogle ScholarCrossref
Raynauld  JP, Buckland-Wright  C, Ward  R,  et al.  Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial.  Arthritis Rheum. 2003;48(2):370-377.PubMedGoogle ScholarCrossref
Guermazi  A, Roemer  FW, Burstein  D, Hayashi  D.  Why radiography should no longer be considered a surrogate outcome measure for longitudinal assessment of cartilage in knee osteoarthritis.  Arthritis Res Ther. 2011;13(6):247.PubMedGoogle ScholarCrossref
Altman  R, Asch  E, Bloch  D,  et al; Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.  Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee.  Arthritis Rheum. 1986;29(8):1039-1049.PubMedGoogle ScholarCrossref
Zhang  Y, Woods  R, Chaisson  CE,  et al.  Alcohol consumption as a trigger of recurrent gout attacks.  Am J Med. 2006;119(9):800.e13-800.e18.PubMedGoogle ScholarCrossref
Kellgren  JH, Lawrence  JS.  The Epidemiology of Chronic Rheumatism: Atlas of Standard Radiographs. Vol 2. Oxford, UK: Blackwell Scientific; 1962.
Tarhan  S, Unlu  Z.  Magnetic resonance imaging and ultrasonographic evaluation of the patients with knee osteoarthritis: a comparative study.  Clin Rheumatol. 2003;22(3):181-188.PubMedGoogle ScholarCrossref
Rubaltelli  L, Fiocco  U, Cozzi  L,  et al.  Prospective sonographic and arthroscopic evaluation of proliferative knee joint synovitis.  J Ultrasound Med. 1994;13(11):855-862.PubMedGoogle ScholarCrossref
Karim  Z, Wakefield  RJ, Quinn  M,  et al.  Validation and reproducibility of ultrasonography in the detection of synovitis in the knee: a comparison with arthroscopy and clinical examination.  Arthritis Rheum. 2004;50(2):387-394.PubMedGoogle ScholarCrossref
Sarmanova  A, Hall  M, Moses  J, Doherty  M, Zhang  W.  Synovial changes detected by ultrasound in people with knee osteoarthritis—a meta-analysis of observational studies.  Osteoarthritis Cartilage. 2016;24(8):1376-1383.PubMedGoogle ScholarCrossref
Atukorala  I, Kwoh  CK, Guermazi  A,  et al.  Synovitis in knee osteoarthritis: a precursor of disease?  Ann Rheum Dis. 2016;75(2):390-395.PubMedGoogle ScholarCrossref
Stratford  PW, Kennedy  DM, Woodhouse  LJ, Spadoni  GF.  Measurement properties of the WOMAC LK 3.1 pain scale.  Osteoarthritis Cartilage. 2007;15(3):266-272.PubMedGoogle ScholarCrossref
Buckland-Wright  JC, Wolfe  F, Ward  RJ, Flowers  N, Hayne  C.  Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: a comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views.  J Rheumatol. 1999;26(12):2664-2674.PubMedGoogle Scholar
Kraus  VB, Vail  TP, Worrell  T, McDaniel  G.  A comparative assessment of alignment angle of the knee by radiographic and physical examination methods.  Arthritis Rheum. 2005;52(6):1730-1735.PubMedGoogle ScholarCrossref
Zhang  M, Driban  JB, Price  LL, Lo  GH, Miller  E, McAlindon  TE.  Development of a rapid cartilage damage quantification method for the lateral tibiofemoral compartment using magnetic resonance images: data from the osteoarthritis initiative.  Biomed Res Int. 2015;2015:634275. doi:10.1155/2015/634275PubMedGoogle Scholar
Zhang  M, Driban  JB, Price  LL,  et al.  Development of a rapid knee cartilage damage quantification method using magnetic resonance images.  BMC Musculoskelet Disord. 2014;15:264.PubMedGoogle ScholarCrossref
Peterfy  CG, Guermazi  A, Zaim  S,  et al.  Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis.  Osteoarthritis Cartilage. 2004;12(3):177-190.PubMedGoogle ScholarCrossref
Xu  L, Hayashi  D, Roemer  FW, Felson  DT, Guermazi  A.  Magnetic resonance imaging of subchondral bone marrow lesions in association with osteoarthritis.  Semin Arthritis Rheum. 2012;42(2):105-118.PubMedGoogle ScholarCrossref
Jungius  KP, Schmid  MR, Zanetti  M, Hodler  J, Koch  P, Pfirrmann  CW.  Cartilaginous defects of the femorotibial joint: accuracy of coronal short inversion time inversion-recovery MR sequence.  Radiology. 2006;240(2):482-488.PubMedGoogle ScholarCrossref
McAlindon  T, LaValley  M, Schneider  E,  et al.  Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial.  JAMA. 2013;309(2):155-162.PubMedGoogle ScholarCrossref
Eckstein  F, Boudreau  RM, Wang  Z,  et al; OAI investigators.  Trajectory of cartilage loss within 4 years of knee replacement—a nested case-control study from the osteoarthritis initiative.  Osteoarthritis Cartilage. 2014;22(10):1542-1549.PubMedGoogle ScholarCrossref
Larsson  E, Erlandsson Harris  H, Larsson  A, Månsson  B, Saxne  T, Klareskog  L.  Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP.  Rheumatology (Oxford). 2004;43(4):428-434.PubMedGoogle ScholarCrossref
Pelletier  JP, DiBattista  JA, Raynauld  JP, Wilhelm  S, Martel-Pelletier  J.  The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis.  Lab Invest. 1995;72(5):578-586.PubMedGoogle Scholar
Houard  X, Goldring  MB, Berenbaum  F.  Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis.  Curr Rheumatol Rep. 2013;15(11):375.PubMedGoogle ScholarCrossref
Altman  RD, Devji  T, Bhandari  M, Fierlinger  A, Niazi  F, Christensen  R.  Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: a systematic review and meta-analysis of randomized trials.  Semin Arthritis Rheum. 2016;46(2):151-159.PubMedGoogle ScholarCrossref
Arroll  B, Goodyear-Smith  F.  Corticosteroid injections for osteoarthritis of the knee: meta-analysis.  BMJ. 2004;328(7444):869.PubMedGoogle ScholarCrossref
Bannuru  RR, McAlindon  TE, Sullivan  MC, Wong  JB, Kent  DM, Schmid  CH.  Effectiveness and implications of alternative placebo treatments: a systematic review and network meta-analysis of osteoarthritis trials.  Ann Intern Med. 2015;163(5):365-372.PubMedGoogle ScholarCrossref
Chao  J, Wu  C, Sun  B,  et al.  Inflammatory characteristics on ultrasound predict poorer longterm response to intraarticular corticosteroid injections in knee osteoarthritis.  J Rheumatol. 2010;37(3):650-655.PubMedGoogle ScholarCrossref
Original Investigation
May 16, 2017

Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial

Author Affiliations
  • 1Division of Rheumatology, Tufts Medical Center, Boston, Massachusetts
  • 2Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  • 3Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts
  • 4Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts
  • 5Division of Musculoskeletal Imaging and Intervention, Tufts Medical Center, Boston, Massachusetts
JAMA. 2017;317(19):1967-1975. doi:10.1001/jama.2017.5283
Key Points

Question  What are the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain in patients with osteoarthritis?

Findings  In a randomized clinical trial of 140 patients with symptomatic knee osteoarthritis, the use of intra-articular triamcinolone compared with intra-articular saline resulted in greater cartilage volume loss. There was no significant difference on knee pain severity between treatment groups.

Meaning  Among patients with symptomatic knee osteoarthritis, intra-articular triamcinolone, compared with intra-articular saline, increased cartilage volume loss and had no effect on knee pain over 2 years.


Importance  Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone.

Objective  To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain.

Design, Setting, and Participants  Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015.

Interventions  Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years.

Main Outcomes and Measures  Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94).

Results  Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of −0.21 mm vs −0.10 mm (between-group difference, −0.11 mm; 95% CI, −0.20 to −0.03 mm); and no significant difference in pain (−1.2 vs −1.9; between-group difference, −0.6; 95% CI, −1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, −0.2%; 95% CI, −0.5% to −0.007%).

Conclusions and Relevance  Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis.

Trial Registration  ClinicalTrials.gov Identifier: NCT01230424