It is well established that damaged articular cartilage has a very limited potential for healing, and articular defects larger than two to four millimeters in diameter rarely heal even with such advances as the use of continuous passive motion26,36,70,98,101,128,130,138,162,163,208. Damage to articular cartilage is a common problem: in one study, it was associated with 16 percent (twenty-one) of 132 injuries of the knee that were sufficient to cause intra-articular bleeding88. Furthermore, damage to a joint surface can lead to premature arthritis128. Twyman et al. prospectively followed twenty-two knees in which osteochondritis dissecans had been diagnosed before skeletal maturity; at an average of thirty-four years, 32 percent had radiographic evidence of moderate or severe osteoarthritis235. Only 50 percent had a good or excellent functional result.

Elderly patients (those who are sixty-five years of age or older) who have an arthritic condition can obtain dramatic relief from pain and restoration of function after total joint replacement. However, such procedures have higher rates of failure in young and early-middle-aged patients (those who are less than forty years old and those who are forty to sixty years old, respectively) than in elderly patients194. This leaves a large group of patients spanning a broad age-group, many of whom are in their prime, for whom there is no currently acceptable and reliable treatment. A typical example is that of a young, healthy individual who has arthrosis or osteochondritis dissecans following an injury to a joint. It might be possible to solve this patient's problems if the lost or damaged segment of articular cartilage inside the involved joint could be regenerated. After it had been restored, the …

Current Concepts Review - The Healing and Regeneration of Articular Cartilage*

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

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

Objective
To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA)

Methods
In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC) Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50-foot walking time Clinical symptoms were assessed just before each injection

Results
At the 1-year and 2-year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time The steroid-injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 005) compared with the saline-injected knees Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide, but not saline (P < 005)

Conclusion
Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted Moreover, long-term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10777

Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: A randomized, double-blind, placebo-controlled trial

OBJECTIVE--To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy. METHODS--Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ). RESULTS--Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p

https://ard.bmj.com/content/annrheumdis/54/5/379.full.pdf

Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response.

The medical treatment of osteoarthritis (OA) in the horse is one of the most utilized therapeutic regimens in the equine practice. It is important to understand the anatomy of synovial joints and the pathophysiology of the disease process to treat OA adequately. Once a thorough understanding of the disease process is comprehended the proper combination of systemic nonsteroidal anti-inflammatory drugs (NSAIDs), intraarticular steroids, viscosupplementation and chondroprotectants can be used to treat the disease and inhibit further progression of degenerative changes to the cartilage surface. The equine practitioner is faced with many choices for controlling inflammation in OA. This review presents the background and appropriate uses of various NSAIDs such as phenylbutazone, flunixin meglumine, ketoprofen, naproxen, and carprofen as well as their associated toxicities. Various steroid formulations exist for intraarticular (IA) administration and much has been learned in the past decade regarding correct dosage, frequency of administrations, indications and toxicity. This review presents IA steroids and their indications in addition to various chondroprotective drugs that also exist to control inflammation and provide viscosupplementation. Data are also given on disease modifying OA drugs such as glucosamine and chondroitin sulphate that have more recently become available to the equine practitioner.

Medical treatment of osteoarthritis in the horse - a review.

The destruction of rabbit articular cartilage after intra-articular injections of hydrocortisone acetate was investigated using histological, biochemical, and tracer methods. Fissures and cysts increased in number as increasing amounts of hydrocortisone were given. A linear decrease of hexosamine to less than 50 per cent after twelve injections was accompanied by insigificant changes in deoxyribonucleic acid and hydroxyproline content. The synthesis of proteoglycans and proteins was reduced to one-third, while the production of collagen dropped to less than one-fifth. The changes in thymidine incorporation were not significant. Based on these data, a model indicating the sequence of events which leads to joint destruction after intra-articular injections of glucocorticoid is proposed.

Alterations of rabbit articular cartilage by intra-articular injections of glucocorticoids.

The recovery of adult rabbit articular cartilage after nine weekly intra-articular injections of hydrocortisone acetate was investigated using biochemical, autoradiographic, and tracer methods. After the cessation of steroid injections, the rates of synthesis of proteoglycans and collagen increased by up to 900 per cent. The increase occurred because of accelerated metabolism of existing cells and an increase (caused by mitosis) in the number of functioning chondrocytes. The proteoglycan concentration only returned to normal values after six months.

N Shepard

Papers

Alterations of rabbit articular cartilage by intra-articular injections of glucocorticoids.

Metabolic recovery of articular cartilage after intra-articular injections of glucocorticoid.