Intra-articular use of hyaluronic acid in osteoarthritis Intervention Hyalgan, Synvisc,Artzal, Suplasyn, BioHy, Orthovisc Table 2 Recent clinical trials using HA Author / Year Lo et al 2004 N trials 22 selected trials Aggarwal et al 2004 Five case series 13 RCTs Synvisc low-molecular-weight HA Wang et al 2004 Axe et al 2005 Goldberg et al 2005 Twenty blinded randomized controlled trials Potential use in the treatment of inﬂammatory arthropathies (eg, acute joint trauma and fractures) A review on a Medline search through June 2004 Hyaluronic acid versus placebo Hyaluronans Hyalgan, Supartz, Synvisc Arrich et al 2005 Twenty-two trials Hyaluronic acid Bellamy et al 2005 Pagnano et al 2005 Thirty-seven trials included comparisons of hyaluronan/hylan and placebo, nine trials included comparisons of intra-articular corticosteroids, and ﬁve trials included comparisons of (NSAIDs) Databases were searched using the terms hyaluronan, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20 Adant,Arthrum H,Artz (Artzal, Supartz), BioHy (Arthrease), Duro- lane, Fermathron, Go-on, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), NRD-101, Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum Hyaluronan, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20 Abbreviations: IA, intra articular; RCT, randomized controlled trials; HA, hyaluronic acid; OA, osteoarthritis. Conclusions Measurable effect when compared with placebo. Highest-molecular-weight HAs may be more. Heterogeneity of these studies limits deﬁnitive conclusions. High-molecular-weight HAs effective. Conﬂicting results with low-molecular- weight. Slower onset of action than intra-articular steroids, but the effect last longer. Therapeutic efﬁcacy and safety Trials limited in design and patient number. Moderate results. Controlled clinical trials are warranted. In addition to relieving the symptoms, HAs also modify the structure of the diseased joint and the rate of OA disease progression. The data available did not allow an appropriate assessment of any end point. Adverse events occurred slightly more often. The effects against ‘placebo’ controls generally supported the efﬁcacy. Delayed effects on pain and function. Comparable efﬁcacy against NSAIDs and longer-term beneﬁts against IA corticosteroids. Few adverse events were reported. Hyaluronans are safe and effective in the treatment of pain. Sodium hyaluronate decrease the rate of deterioration of joint structure OA disease progression, at least early in the evolution of the disease process (Ohkawara et al 2000). Based on the aforementioned analyses, viscosupple- mentation is an effective treatment for OA of the knee with beneﬁcial effects on pain, function and patient global assess- ment at different post injection periods but especially at the 5 to 13 week post injection period with a dramatic effect on the reduction of NSAIDs monthly consumption. However, there are few randomized head-to-head com- parisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. In some analyses, viscosupplements were comparable in efﬁcacy to systemic forms of treatment, with more local reac- tions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the Clinical Interventions in Aging 2008:3(2) HA class of products in the treatment of knee OA (Lo et al 2003). In one systematic review, IA HA has not been proven clinically effective and may be associated with minimal and transient risk of adverse events (Arrich et al 2005). At present no case of septic arthritis has been reported in any clinical trial. Most adverse events are minor and transient at the injection site. Painful post-injection reac- tion occurred in 1%–2% of patients, the pain did not last more than 72 hours. Systemic allergic reactions due to individual hypersensitivity were rarely recorded. Therefore viscosupplementation seems to be an efﬁcacious and safe treatment. The heterogeneity of these studies limits definitive conclusions on different treatment regimen with diverse molecular weight HA but in our opinion we think that the different HA products act with the same class effect (Axe and Shields 2005). 367