Hyaluronic acid for the treatment of knee osteoarthritis: long-term outcomes from a naturalistic primary care experience

Am J Phys Med Rehabil. 2005 Apr;84(4):278-83; quiz 284, 293. doi: 10.1097/01.phm.0000156899.18885.06.


Objective: Intraarticular hyaluronic acid is indicated for patients with osteoarthritis of the knee. However, clinical experience, especially efficacy and adverse events, with repeated injection series in the long term are limited.

Design: Patients were referred to a large primary care center for management of osteoarthritis of the knee. All were naive to intraarticular hyaluronic acid therapy and met our entry criteria, including resting visual analog scale pain of > 45 mm, radiographic confirmation of unilateral knee grade 1-3 osteoarthritis, and willingness to receive intraarticular therapy. Patients received a three-intraarticular injection series with Suplasyn (10 mg/ml, 2-ml injection) over 3 wks. Patients were instructed to return for consideration of repeat injection series based on their perception of pain restricting daily activity and a resumption of severity similar to their initial presentation. This prospective naturalistic cohort was followed for 6.7 yrs. Patients completed baseline assessment of rest and walking visual analog scale pain (primary efficacy variable), completed a 5-point categorical global satisfaction score, and recorded adverse events and concomitant therapeutic modality use at each study visit. Patients returned for consideration of a repeat injection series based on their perception of symptom severity and were eligible if their resting visual analog scale pain was > 45 mm. The three-injection series and data collection were repeated, and again, patients were given similar instructions regarding consideration of a third injection series.

Results: Of 897 referral patients, 537 (mean age, 68 +/- 8 yrs; mean duration of symptoms, 7.4 +/- 4.1 yrs) met our criteria, and only 21 patients did not return for a second injection series. The mean time between first and second series was 27 +/- 7 wks. The change in walking visual analog scale pain was significantly improved from baseline after the first series (81.3%, P < 0.001) and second series (86.7%, P < 0.0001). Similarly, resting visual analog scale pain was significantly decreased from baseline after the first (P < 0.001) and second (P < 0.001) series, and patient satisfaction was significantly improved with each injection series (P < 0.03 and P < 0.01). Very few adverse events were recorded and were limited to local pain and swelling. Use of concomitant therapeutic modalities at presentation for a second injection series included: nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 medications (37%), acetaminophen (31%), oral nutraceuticals (12%), and physical therapy and bracing (12%).

Conclusions: Intraarticular hyaluronic acid injections were highly effective in improving resting and walking pain in patients with osteoarthritis of the knee on a first and a second treatment series. Duration of symptom control was about 6 mos, and the therapy was highly satisfactory to patients and was associated with very few local adverse events and limited use of concomitant therapeutic modalities. These data support the potential role of intraarticular hyaluronic acid as an effective long-term therapeutic option for patients with osteoarthritis of the knee.

Publication types

  • Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Male
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Pain Measurement
  • Patient Satisfaction
  • Prospective Studies
  • Rest / physiology
  • Severity of Illness Index
  • Treatment Outcome
  • Walking / physiology


  • Adjuvants, Immunologic
  • Hyaluronic Acid