Hyaluronic Acid and Dextrose Coinjections Improve Knee Osteoarthritis Symptoms

knee injection, Hyaluronic acid
knee injection
Researchers investigated whether intra-articular coinjection with hypertonic dextrose improves hyaluronic acid therapy outcomes for patients with knee osteoarthritis.

Coinjections of hyaluronic acid (HA) and dextrose were shown to improve stair-climbing and physical function in patients with knee osteoarthritis (OA) at 6 months, according to study results published in Archives of Physical Medicine and Rehabilitation.

In a prospective, randomized, double-blind trial (ClinicalTrials.gov Identifier: NCT03238183) conducted at a medical center in Taiwan, researchers determined whether intra-articular coinjection with hypertonic dextrose enhances the outcomes of HA prolotherapy in patients with knee OA.

The primary study outcomes were performance-based measures of physical function, including regular and fastest walking speed using the 10-meter walk, stair-climbing time, and chair-raising time. Secondary outcomes included the Chinese versions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) visual analog scale, which evaluated pain, stiffness, and physical function, and the Knee Injury and Osteoarthritis Outcome Score (KOOS), which measured pain, function, disability, and quality of life.

A total of 104 patients who fulfilled American College of Rheumatology (ACR) clinical and radiographic criteria for knee OA (a Kellgren-Lawrence score of 2 or 3) were enrolled in the study. All participants were aged between 40 and 85 years, received 3 weeks of treatment and 6 months of follow-up, and were recommended to avoid the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during the study period. The participants were randomly assigned in a 1:1 ratio to the treatment group (HA plus hypertonic dextrose coinjections) or the control group (HA plus normal saline coinjections). Ultrasound-guided knee intra-articular injections were administered once-weekly for 3 weeks.

Results of the study showed significant intergroup difference-in-difference at 6 months in regular walking speed (P <.001), fastest walking speed (P <.001), stairs ascent time (P =.038), and chair-rising time (P =.023). Stair-climbing time (-1.6; 95% CI, -0.38 to -1.17; P =.38) was the only significant intergroup difference-in-difference favoring the treatment at 6 months. The group x time interaction effects that favored the treatment group were reported in regular walking speed (P =.001), fastest walking speed (P =.011), and chair-rising time (P =.038).

Regarding secondary outcomes, significant intergroup difference-in-differences at 6 months were observed in WOMAC stiffness (P =.044) and physical function (P =.045), as well as KOOS pain (P =.001). Of these measures, the only significant intergroup difference-in-difference that favored the treatment group at 6 months was WOMAC physical function (-21.1; 95% CI, -1.85 to 0.94; P =-.045).

The study was limited by the fact that the sample size was relatively small. Because the follow-up duration was short, the long-term (ie, ≥1 year) therapeutic and adverse effects could not be evaluated.

The study authors concluded, “Prolotherapy is a simple, safe, and inexpensive treatment modality and can easily be administered in clinical settings. Therefore, HA and dextrose coinjections can improve standard care and provide adjuvant therapy for patients with knee OA.”


Hsieh R-L, Lee W-C. Effects of intra-articular coinjections of hyaluronic acid and hypertonic dextrose on knee osteoarthritis: a prospective, randomized, double-blind trial. Arch Phys Med Rehabil. Published online April 16, 2022. doi:10.1016/j.apmr.2022.04.001