Steroid injections, which are often used to treat pain in knee osteoarthritis (KOA), may actually make arthritis worse, according to two new studies comparing steroid injections with hyaluronic acid, another common therapy to treat pain in the condition. The findings were presented on November 29, 2022, at RSNA 2022, the annual meeting of the Radiological Society of North America (RSNA) in Chicago.

Osteoarthritis (OA) is the most common kind of arthritis, and it’s estimated that 38 to 45 percent of people develop KOA over their lifetime, according to the Centers for Disease Control and Prevention (CDC). More than 10 percent of patients with knee osteoarthritis seek pain relief through corticosteroid or hyaluronic acid injections.

Steroid Injections Significantly Associated With Progression of Knee OA

Researchers in both studies used participants from the Osteoarthritis Initiative, a multicenter, longitudinal, observational study of nearly 5,000 participants with KOA, currently in its 14th year of follow-up.

The first study, conducted by the researchers at the University of California in San Francisco, included 210 participants; a total of 70 subjects received intraarticular injections- 44 with steroids and 26 with hyaluronic acid. The remaining 140 participants (the control group) didn’t get any injections.

Hyaluronic acid injections are used to reduce knee pain, especially when other treatments haven’t been effective. It’s theorized that the injections could help lubricate joints where cartilage has been eroded by osteoarthritis.

The treatment and control groups were matched by age, sex, body mass index, pain and physical activity scores, and severity of their knee osteoarthritis.

All the participants had an MRI at the time of the injection and two years before and after, and the researchers tracked osteoarthritis progression by comparing the imaging scores from the initial scans and two-year follow-up scans.

Investigators found that steroid knee injections were significantly associated with the overall progression of osteoarthritis in the knee, specifically in the lateral meniscus, lateral cartilage, and medial cartilage.

In contrast, hyaluronic acid knee injections were not significantly associated with the progression of osteoarthritis in the knee. Compared with the control group, the group who received hyaluronic injections showed a decreased progression of osteoarthritis, specifically in bone marrow lesions.

“While both corticosteroid and hyaluronic acid injections are reported to help with symptomatic pain relief for knee osteoarthritis, our results conclusively show that corticosteroids are associated with significant progression of knee osteoarthritis up to two years post-injection and must be administered with caution,” said coauthor Upasana Upadhyay Bharadwaj, MD, a research fellow in the department of radiology at University of California in San Francisco, in a press release. The results suggest that hyaluronic acid may slow down progression of knee osteoarthritis while also providing symptomatic relief, he added.

X-Ray Reveals Greater KOA Progression at 2 Years in Group That Received Steroid Injections

In the second study, researchers conducted an observational study that compared the radiographic progression (the most commonly used imaging method to diagnose OA) of osteoarthritis in patients who received injections of corticosteroids versus hyaluronic acid.

Researchers chose a group of 150 patients with similar baseline characteristics from the Osteoarthritis Initiative database, including 50 patients who received corticosteroid injections, 50 who received hyaluronic acid injections, and 50 who were not injected over a three-year time period. The groups were matched by sex, body mass index and X-Ray findings.

Researchers compared X-ray images of the knees at baseline and two years later with detect changes in joint space narrowing, formation of bone spurs, and bone thickening around the knee cartilage.

Compared with patients who received an injection of hyaluronic acid or no injections, those who had a steroid injection had significantly more osteoarthritis progression, including medial joint space narrowing, a hallmark of KOA.

“Even though imaging findings for all patients were similar at baseline, the imaging hallmarks of osteoarthritis were worse two years later in patients who received corticosteroid injections compared with patients who received hyaluronic acid injections or no treatment at all,” said coauthor Azad Darbandi, a researcher and medical student at Chicago Medical School of Rosalind Franklin University of Medicine and Science. The results suggest that hyaluronic acid injections should be further explored for the management of KOA symptoms, and that steroid injections should be utilized with more caution, said Darbandi.

Experts Agree: Better Options for Treating Knee OA Are Needed

Both studies have a small sample size and are non-randomized — typically these types of studies are more likely to have biases and statistical errors, says Bruno R. da Costa, PhD, associate professor at the Institute of Health Policy, Management, and Evaluation at the University of Toronto, whose research interests include osteoarthritis. Dr. da Costa was not involved in either of the studies.

MRI assessments are costly and so it’s often not feasible to use them in research, says da Costa. “The use of Osteoarthritis Initiative data to address this research question is a clever way to go about it,” he says. Although the level of the evidence generated is rather low given the methodological shortcomings, these findings could be used to help further research in larger, randomized trials, he says.

Steroid injections can be harmful if not used properly, says da Costa. “There is good evidence that steroids are more effective than placebo in the short-term but not in the mid to long term.”

There is also conclusive evidence that hyaluronic acid injections aren’t better than a placebo injection to treat osteoarthritis pain, says da Costa. “At the same time, there is strong evidence that this treatment is associated with serious adverse events,” he says.

Da Costa was the coauthor of meta-analysis published in the BMJ in July 2022 that found hyaluronic acid injections did not lead to a clinically significant reduction in pain in KOA and were associated with an increased risk of serious adverse events compared with placebo. The authors of that study wrote, “The findings do not support broad use of viscosupplementation (with hyaluronic acid injections) for the treatment of knee osteoarthritis.”