Successful nonoperative management of chronic osteoarthritis pain of the knee: safety and efficacy of retreatment with intra-articular hyaluronans

Osteoarthritis Cartilage. 2005 Sep;13(9):751-61. doi: 10.1016/j.joca.2005.04.012.


Context: Although there are many nonsurgical therapies available for the treatment of pain associated with osteoarthritis (OA), their long-term use and safety have not been systematically followed. Intra-articular hyaluronan therapy has been used in the treatment of symptoms associated with OA of the knee with a very favorable safety profile. Five intra-articular hyaluronan products are approved in the US. No systematic review of the safety and efficacy of their chronic use has been reported.

Objective: To evaluate the literature on the efficacy and safety of repeat courses of hyaluronan therapy in patients with OA of the knee.

Data sources: MEDLINE, EMBASE, searched through October 2004.

Study selection: Databases were searched using the terms hyaluronan, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20, osteoarthritis, adverse events, repeat treatment, and multiple courses.

Data synthesis: There are some data that support the benefit and safety of repeat treatment for all products. Data also indicate that one formulation of sodium hyaluronate (molecular weight [MW] 500-730 kDa) is well tolerated and as effective after multiple courses of treatment as it is after a single course. There is also clinical evidence that prolonged use of sodium hyaluronate (MW 500-730 kDa) may significantly decrease the rate of deterioration of joint structure. Localized severe acute inflammatory reactions reported with repeated treatment in some patients are not a class effect but may be linked to physicochemical characteristics of hylan-based treatment.

Conclusions: Repeat courses of the hyaluronans are safe and effective in the treatment of pain associated with OA of the knee.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Chronic Disease
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / therapeutic use
  • Injections, Intra-Articular
  • Osteoarthritis, Knee / drug therapy*
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Treatment Outcome


  • Hyaluronic Acid