Comparison of Low-, Moderate-, and High-Molecular-Weight Hyaluronic Acid Injections in Delaying Time to Knee Surgery

J Arthroplasty. 2017 Oct;32(10):2952-2957.e21. doi: 10.1016/j.arth.2017.04.041. Epub 2017 May 2.


Background: We compared the effectiveness of low-molecular-weight (MW) hyaluronic acid (HA) injections (LMWHA), moderate-MW HA injections (MMWHA), and high-MW HA injections (HMWHA) for prevention or delay of knee surgery in patients with knee osteoarthritis.

Methods: An observational cohort study using LifeLink Plus claims (2006-2015) was used. The primary outcome measure of the study included all surgical interventions of the knee. The secondary outcome measures were the following: (1) unicompartmental knee arthroplasty or total knee arthroplasty and (2) total knee arthroplasty only. A high-dimensional propensity score (hdPS) using 1:1 matching was used to adjust for confounding. The likelihood of each outcome was assessed using Cox proportional hazard models.

Results: A cohort of 30,417 incident HA users with knee osteoarthritis met our inclusion-exclusion criteria. There was no difference in the likelihood of composite surgical events between LMWHA users (hazard ratio, 0.939; 95% confidence interval, 0.870-1.013) and MMWHA users (hazard ratio, 1.032; 95% confidence interval, 0.952-1.119) when compared with HMWHA users in a matched hdPS analysis. However, a significantly lower likelihood for all outcome measures was demonstrated in LMWHA and MMWHA users compared with HMWHA users when hdPS was not used.

Conclusion: There was no significant difference in the likelihood of surgical interventions between LMWHA, MMWHA, and HMWHA users after accounting for empirically derived confounders.

Keywords: arthroplasty; comparative effectiveness; high-dimensional propensity score; hyaluronic acid; knee osteoarthritis; knee surgery.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Arthroplasty, Replacement, Knee
  • Cohort Studies
  • Female
  • Humans
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Knee Joint / surgery
  • Male
  • Middle Aged
  • Molecular Weight
  • Orthopedic Procedures
  • Osteoarthritis, Knee / therapy*
  • Propensity Score
  • Viscosupplements / therapeutic use*


  • Viscosupplements
  • Hyaluronic Acid