Effects of Intra-articular Coinjections of Hyaluronic Acid and Hypertonic Dextrose on Knee Osteoarthritis: A Prospective, Randomized, Double-Blind Trial

Arch Phys Med Rehabil. 2022 Aug;103(8):1505-1514. doi: 10.1016/j.apmr.2022.04.001. Epub 2022 Apr 16.


Objective: To determine whether intra-articular coinjection with hypertonic dextrose improves the outcome of hyaluronic acid (HA) prolotherapy for knee osteoarthritis (OA).

Design: Prospective, randomized, double-blind trial.

Setting: Medical center in Taiwan.

Participants: In total, 104 participants who fulfilled the American College of Rheumatology clinical and radiographic criteria for knee OA with a Kellgren-Lawrence score of 2 or 3 were recruited (N=104).

Interventions: The participants were blocked randomized to the treatment (HA and hypertonic dextrose) or control (HA and normal saline) group. Ultrasound-guided knee intra-articular injections were administered once a week for 3 weeks.

Main outcome measures: The primary outcomes were performance-based physical function measures (regular and fastest walking speed, stair climbing time, and chair rising time), and the secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). The outcome measures were assessed before the injections and at 1 week and 1, 3, and 6 months after the injections. The data were analyzed through repeated-measures analysis of covariance.

Results: Significant intergroup difference-in-differences favoring the treatment group were observed for improvements in stair climbing time (-1.6; 95% confidence interval, -8.56 to 4.16; P=.38) and WOMAC physical function (-21.2; 95% confidence interval, -126.05 to 103.83; P = .045) at 6 months. The group×time interaction effects favored the treatment group for regular (P=.001) and fastest walking speed (P=.001) and chair rising time (P=.038); WOMAC stiffness (P < .001) and physical function (P = .003); and KOOS for pain (P = .035), other symptoms (P=.022), and quality of life (P=.012).

Conclusions: Compared with HA plus normal saline coinjections, HA plus dextrose coinjections resulted in more significant improvements in stair climbing time and physical function at 6 months, effectively decreased pain, and improved physical function and physical functional performance from 1 week to 6 months. HA plus dextrose coinjections could be a suitable adjuvant therapy for patients with knee OA.

Trial registration: ClinicalTrials.gov NCT03238183.

Keywords: Glucose; Hyaluronic acid; Osteoarthritis, knee; Prolotherapy; Rehabilitation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Double-Blind Method
  • Glucose
  • Humans
  • Hyaluronic Acid / therapeutic use
  • Injections, Intra-Articular
  • Osteoarthritis, Knee*
  • Pain / drug therapy
  • Prospective Studies
  • Quality of Life
  • Saline Solution / therapeutic use
  • Treatment Outcome


  • Saline Solution
  • Hyaluronic Acid
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT03238183