Original research: long-term efficacy and safety of periarticular hyaluronic acid in acute ankle sprain

Phys Sportsmed. 2009 Apr;37(1):64-70. doi: 10.3810/psm.2009.04.1684.


The objectives of this study were to determine the long-term efficacy and safety of periarticular hyaluronic acid (HA) injections in acute lateral ankle sprain. A randomized, controlled, prospective trial in a primary sports medicine and emergency practice involved 158 competitive athletes who suffered an acute grade 1 or 2 lateral ankle sprain, and who were randomly assigned within 48 hours of injury. Patients were randomly assigned at baseline to periarticular injection with HA + standard of care (rest, ice, elevation, and compression [RICE]) or placebo injection (PL) + standard of care (RICE) treatment at baseline assessment and day 4 after injury. Follow-up was at 30, 90, and 712 days after treatment. Assessments at baseline and days 4, 8, 30, 90, and 712 included visual analogue scale (VAS) (0-10 cm) pain on weight bearing and walking 20 m, patient global assessment of ankle injury (5-point categorical scale), patient satisfaction with treatment (5-point categorical scale), time to return to pain-free and disability-free sport, recurrent ankle sprain, total number of days missing from primary sport activity, and adverse events (AEs). Time to intervention was 39 +/- 4 hours with no difference between groups. A significant reduction in VAS pain on both weight bearing and walking was observed at all follow-up assessments for HA compared with PL (P < 0.001). Time to pain-free and disability-free return to sport was 11 (+/- 8) versus 17 (+/- 8) days for HA and PL, respectively (P < 0.05). At 24 months, in the PL versus HA group, there were 2 versus 0 lower limb fractures, 16 versus 7 second ankle sprains (P < 0.05), 3 versus 1 third ankle sprains, and a significantly greater number of days missing primary sport activity (41 vs 21; P < 0.002). Significantly greater patient satisfaction was also observed for HA versus PL at all follow-up assessments. No serious AEs were recorded throughout follow-up. Periarticular HA treatment for acute ankle sprain was highly satisfactory in the short and long term versus PL. This was associated with reduced pain, more rapid return to sport, fewer recurrent ankle sprains, fewer missed days from sport, and with few associated AEs to 24 months.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Ankle Injuries / drug therapy*
  • Chi-Square Distribution
  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Male
  • Pain Measurement
  • Placebos
  • Sprains and Strains / drug therapy*
  • Treatment Outcome
  • Viscosupplements / administration & dosage
  • Viscosupplements / therapeutic use*


  • Placebos
  • Viscosupplements
  • Hyaluronic Acid