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Intra-Articular Therapy in Osteoarthritis I Uthman, J-P Raynauld, B Haraoui

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Intra-Articular Therapy in Osteoarthritis I Uthman, J-P Raynauld, B Haraoui 449 REVIEW Intra-articular therapy in osteoarthritis I Uthman, J-P Raynauld, B Haraoui ............................................................................................................................. Postgrad Med J 2003;79:449–453 The medical literature was reviewed from 1968–2002 symptomatic treatment of osteoarthritis.1 A sur- using Medline and the key words “intra-articular” and vey of rheumatologists in the US suggested that “ ” - more than 95% use this treatment sometimes and osteoarthritis to determine the various intra articular more than half of them, frequently.2 Intra- therapies used in the treatment of osteoarthritis. articular corticosteroids are also recommended in Corticosteroids and hyaluronic acid are the most the recent American College of Rheumatology frequently used intra-articular therapies in osteoarthritis. guidelines for the management of acute knee pain in patients with osteoarthritis.3 Other intra-articular substances such as orgotein, Corticosteroids exert their anti-inflammatory radiation synovectomy, dextrose prolotherapy, silicone, action by interrupting the inflammatory and saline lavage, saline injection without lavage, analgesic immune cascade at several levels including: impairment of antigen opsonisation, interference agents, non-steroidal anti-inflammatory drugs, with inflammatory cell adhesion and migration glucosamine, somatostatin, sodium pentosan through vascular endothelium, interruption of polysulfate, chloroquine, mucopolysaccharide cell-cell communication by alteration of release or antagonism of cytokines (interleukin-1), impair- polysulfuric acid ester, lactic acid solution, and thiotepa ment of leukotriene and prostaglandin synthesis, cytostatica have been investigated as potentially inhibition of production of neutrophil superoxide, therapeutic in the treatment of arthritic joints. Despite the metalloprotease and metalloprotease activator (plasminogen activator), and decreased immu- lack of strong, convincing, and reproducible evidence noglobulin synthesis.4 that any of the intra-articular therapies significantly Earlier studies have reported that cortico- alters the progression of osteoarthritis, corticosteroids steroids injections may suppress cartilage prote- oglycan synthesis, worsen cartilage lesion, or even and hyaluronic acid are widely used in patients who cause degenerative lesions in normal cartilage.5 In have failed other therapeutic modalities for lack of more recent reports, using animal model (rabbits efficacy or toxicity. As a practical approach for a knee and guinea pigs) of osteoarthritis, several investi- gators have reported that low dose intra-articular with effusion, steroid injections should be considered corticosteroids (sufficient to suppress catabolism) while the presence of symptomatic “dry” knees may normalised cartilage proteoglycan synthesis and favour the hyaluronic acid approach. The virtual significantly reduced the incidence and severity of cartilage erosions and osteophyte formation.6 absence of serious side effects, coupled with the In a study using the Pond-Nuki dog model of perceived benefits, make these approaches attractive. osteoarthritis, an animal model which closely resembles the changes observed in human osteo- .......................................................................... arthritis, intra-articular injection of low dose tri- amcinolone acetonide (5 mg), a long acting steoarthritis is a disease characterised by corticosteroid preparation, reduced osteophyte a mixture of degradative and reparative formation and cartilage lesions and exerted a Oprocesses in the articular cartilage, protective effect on cartilage histological changes subchondral bone associated with marginal os- (confined the spread of cartilage erosions, re- teophyte formation, and low grade inflammation. duced the formation of fissures and cell clones, 6 Osteoarthritis involves mainly the hips, knees, and preserved matrix proteoglycans). In a more spine, and the interphalangeal joints. Its clinical recent study, also using a dog experimental model presentation is usually monoarticular or oligoar- of osteoarthritis, intra-articular injections with See end of article for ticular with fluctuations in intensity and localisa- methylprednisolone acetate (MPA) significantly authors’ affiliations reduced the incidence and size of osteophytes and ....................... tion over time. It is therefore logical to consider local therapeutic modalities in order to avoid the severity of cartilage lesions; this was associ- Correspondence and untoward systemic effects. Several compounds ated with a decrease in chondrocyte stromelysin 7 reprint requests to: Dr Imad have been used intra-articularly in open label and synthesis. The beneficial effect of corticosteroids W Uthman, American on cartilage can be due to several possible mecha- University of Beirut Medical in double blind randomised clinical trials. In this Centre, PO Box: article we review the various intra-articular nisms: in vivo suppression of metalloproteases 113–6044, Hamra, therapeutic modalities used in the treatment of synthesis (probably by suppression of gene 1103 2090, Beirut, osteoarthritis. Lebanon; [email protected] ................................................. CORTICOSTEROIDS Abbreviations: kD, kilodalton; MPA, methylprednisolone Submitted Corticosteroids are very potent anti- 26 November 2002 acetate; NaPP, sodium pentosan polysulfate; NSAIDs, Accepted 17 March 2003 inflammatory agents. Intra-articular injections non-steroidal anti-inflammatory drugs; WOMAC, Western ....................... have been used for nearly five decades for the Ontario and McMaster Universities Osteoarthritis Index www.postgradmedj.com 450 Uthman, Raynauld, Haraoui expression), decreasing the synthesis of possible physiological HYALURONIC ACID activators such as plasminogen activator/plasmin or by Viscosupplementation is a novel, safe, and possibly effective increasing the level of tissue inhibitors of metalloproteases, or form of local treatment for osteoarthritis.21 It aims at supply- by suppression of the synthesis of synovial factors such as ing replacement hyaluronic acid into the joint space to return interleukin-1.6–8 the elasticity and viscosity of the synovial fluid to normal.22 In humans, repeated corticosteroid injections in knees of Hyaluronic acid, a polysaccharide consisting of a long chain of patients with chronic arthritis presented no evidence of disaccharides (β-D-glucuronyl-β-D-N-acethylglucosamine), is destruction or accelerated deterioration.9 In a recent study, a a natural component of cartilage and plays an essential part in single intra-articular injection of triamcinolone acetonide to the viscoelastic properties of the synovial fluid. Because of its patients with knee osteoarthritis provided short term pain hyaluronic acid content, joint fluid acts as a viscous lubricant relief.10 Increased benefit was associated with both clinical during slow movement of the joint, as in walking, and as an evidence of joint effusion and successful aspiration of synovial elastic shock absorber during rapid movement, as in running. fluid at the time of injection.10 It is considered not only a joint lubricant, but also a To demonstrate the difference in outcome and rate of carti- physiological factor in the trophic status of cartilage. lage degradation among patients with knee osteoarthritis Hyaluronic acid has a very high water binding capacity: when treated with intra-articular corticosteroid injections, we have 1 g of hyaluronic acid is dissolved in physiological saline, it studied 70 patients fulfilling the American College of occupies three litres of solution.23 The estimated total Rheumatology criteria for primary knee osteoarthritis who hyaluronic acid in a human knee joint is from 4–8 mg.23 were randomly chosen to receive intra-articular injections of a Intra-articular injections of hyaluronic acid with a molecu- corticosteroid (40 mg triamcinolone acetonide ) or a vehicle, at lar weight between 500 and 750 kilodaltons (kD) have been three month intervals, for a prospective period of two years. studied using corticosteroid injections24–28 or NSAIDs29 as con- Patients with a standing radiograph showing a joint space trol treatment, and by conducting placebo controlled clinical width of the knee internal compartment of less than 2 mm trials.30–37 These studies suggested that intra-articular injection were excluded. Conventional treatment (analgesics and of hyaluronic acid may improve the clinical condition and have non-steroidal anti-inflammatory drugs (NSAIDs) except a long term beneficial effect in knee osteoarthritis patients indomethacin) was prescribed according to the practitioner’s especially if osteoarthritis was less than moderate in usage and was systemically recorded. The radiological grade.30–37 A review by Maheu looked at five different clinical progression of joint space narrowing of the injected knee over trials, comparing different regimens of Hyalgan (a hyaluronan two years was our primary outcome variable. The progression preparation; Sanofi-Synthelabo) versus corticosteroid injec- was assessed blindly at one and two years of treatment with tions in the osteoarthritis knee, with follow ups from 2–12 the validated Buckland-Wright protocol. Clinical evaluation of months.38 One study showed initial superiority of Hyalgan the patients using validated measures Western Ontario and over corticosteroid injections and in three studies, equal McMaster Universities Osteoarthritis Index (WOMAC), global efficacy
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