BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intra-articular (IA)) may relieve inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee. 
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE, EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched.
SELECTION CRITERIA: Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk
AUTHORS CONCLUSIONS : The short-term benefit of IA corticosteroids in treatment of knee OA is well established, and few side effects have been reported. Longer
term benefits have not been confirmed based on the RevMan analysis. The response to HA products appears more durable. In this review, some discrepancies were observed between the RevMan 4.2 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.2. Future trials should have standardised
outcome measures and assessment times, run longer, investigate different patient subgroups, and clinical predictors of response (those associated with inflammation and structural damage)

https://espace.library.uq.edu.au/view/UQ:80236/UQ80236_OA.pdf

Intraarticular corticosteroid for treatment of osteoarthritis of the knee

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, 394) 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 -021 mm vs -010 mm (between-group difference, -011 mm; 95% CI, -020 to -003 mm); and no significant difference in pain (-12 vs -19; between-group difference, -06; 95% CI, -16 to 03) 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, -02%; 95% CI, -05% to -0007%) 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 ClinicalTrialsgov Identifier: NCT01230424

/pdf/effect-of-intra-articular-triamcinolone-vs-saline-on-knee-4nnrdiquzn.pdf

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

BACKGROUND

Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005.

OBJECTIVES

To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety.

SEARCH METHODS

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors.

SELECTION CRITERIA

We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions.

DATA COLLECTION AND ANALYSIS

We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis.

MAIN RESULTS

We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46).

AUTHORS' CONCLUSIONS

Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

/pdf/intra-articular-corticosteroid-for-knee-osteoarthritis-48fkz80qr5.pdf

Intra‐articular corticosteroid for knee osteoarthritis

https://www.amjmed.com/article/0002-9343(85)90057-9/pdf

Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus

Twelve horses with traumatic arthritis were treated with intraarticular injection of hyaluronic acid mixed with cortisone and the results compared with 6 horses treated only with cortisone. There was a significantly better improvement in the group injected with a mixture of hyaluronic acid and cortisone. Further studies have given the same results in traumatic arthritis in horses if hyaluronic acid alone is injected. After injection of hyaluronic acid a large number of granulated monocytes appeared in the synovial fluid, but no inflammatory signs were observed. It is possible that this macrophage invasion is instrumental in producing improvement in the condition of the joint. The injected hyaluronic acid may also adhere to the surface of articular cartilage producing an “clastic cushion” protecting the cartilage surface. Experimental mechanical damage was also inflicted on the surface of articular cartilage in dogs and monkeys, and smoother healing was achieved if hyaluronic acid was injected into the joints after the damage. Injections of hyaluronic acid seem to be of value in treating traumatic arthritis or similar conditions.

/pdf/hyaluronic-acid-in-synovial-fluid-vi-effect-of-intra-3a2r0vndd8.pdf

Hyaluronic Acid in Synovial Fluid: VI. Effect of Intra-Articular Injection of Hyaluronic Acid on the Clinical Symptoms of Arthritis in Track Horses

Alain, M., Saint-Etienne, J., and Reynes, V. (1949). Med. trop., 9, 119. Blanc, G., and Baltazard, M. (1941). Presse mdd., 49, 1293. Couture E. (1935). Rev. Hyg. Mid. pr&v., 57, 190. Grant, A., and Barwell, C. (1943). Lancet, 1, 199. Gutner, L. B., and Fisher, M. W. (1948). Ann. intern. Med., 28, 1157. de Moor, C. E., Soekarnen, and van der Walle, N. (1932). Geneesk. T. Ned.-Ind., 72, 1618. Olds, R. J., and Lewis, F. A. (1954). Aust. vet. J., 30, 253. Stanton, A. T., and Fletcher, W. (1932). Studies from the In.stitute for Medical Research, F.M.S., No. 21. Bale, Sons and Danielsson, London. Sudibyo, R. M. S. (1938). Geneesk. T. Ned.-Ind., 78, 1424. Whitmore, A (1913). J. Hyg. (Camb.), 13, 1. and Krishnaswami, C. S. (1912). Indian med. Gaz., 47, 262.

https://www.bmj.com/content/bmj/1/5127/952.full.pdf

Charcot's arthropathy following intra-articular hydrocortisone.

https://ard.bmj.com/content/annrheumdis/19/3/257.full.pdf

Intra-Articular Therapy in Osteo-Arthritis: Comparison of Hydrocortisone Acetate and Hydro-Cortisone

Intra-articular therapy in rheumatoid arthritis: comparison of hydrocortisone tertiary butyl acetate and hydrocortisone acetate.

SIR,-Professor J. L. Hollander (20 March, p. 794) has rendered a service to medicine in introducing intra-articular corticosteroids in the treatment of rheumatoid arthritis, a debt which we have acknowledged.' He has remained an enthusiastic advocate of this useful treatment, but he does not serve his cause well in depreciating the work of those who have sounded a cautionary note. He claims to have had more experience of intra-synovial steroid injections than we, without knowledge of the total experience we have in fact had. Indeed, one of us (S. J. H.) was carrying out intra-articular aspira'tions and injections using procaine lactic acid long before the cortisone era. We were sorry to note that he could obtain no fluid from the approach to the knee-joint used by us in patients with osteoarthritis, since we find no such difficulty when fluid is present. The sweeping deduction that \" no fluid can be obtained with this method from any osteoarthritic knees \" is therefore a false generalization. It is important to note what we did state in our papers rather than what we are claimed to have stated. We did not say that \" intraarticular steroid therapy is not palliative in osteoarthritis.\" What we stated2 was that \" in the therapy of osteoarthritis of the knees, when the choice lies between short wave diathermy and intra-articular therapy, it would appear that short-wave diathermy should be given first.\" Nor have we suggested that \" intraarticular steroid therapy . . . is so dangerous in rheumatoid arthritis that it should be abandoned.\" What we have in fact said3 is \" intra-articular hydrocortisone acetate and tertiary butyl acetate have a valuable role to play, particularly in patients with rheumatoid arthritis. If a course of such intra-articular therapy is contemplated, however, strict radiological supervision is essential.\" Since we have seen no facts to contradict the careful observations which form the basis of these conclusions, we have not retracted them. May we also be permitted to add that because a paper -is \" studded with controls and statistical analyses \" this does not detract from its value, as some might infer from Professor Hollander's letter. Indeed there are some who are of the opinion that a scientific approach to medicine demands careful control and statistical analysis, particularly in the assessment of treatment of diseases where bias and chance have so commonly led to favourable reports of remedies now discarded. We are not in fact completely out of line with all other reports, as Dr. Hollander's letter suggests, and we would draw his attention to a detailed study4 of 181 patients with osteoarthritis reaching conclusions similar to ours.-We are, etc., V. WRIGHT. S. J. HARTFALL. G. N. CHANDLER. Rheumatism Research Unit, University of Leeds, Leeds 2.

https://www.bmj.com/content/bmj/1/5441/1065.2.full.pdf

G. N. Chandler

Papers

Charcot's arthropathy following intra-articular hydrocortisone.

Intra-Articular Therapy in Osteo-Arthritis: Comparison of Hydrocortisone Acetate and Hydro-Cortisone

Intra-articular therapy in rheumatoid arthritis: comparison of hydrocortisone tertiary butyl acetate and hydrocortisone acetate.

Efficacy of Intra-articular Steroid