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CHICAGO -- Common treatments for people living with osteoarthritis of the knee -- such as steroid injections or anti-inflammatory agents -- reduced pain, but were also associated with increasing damage to the joints, researchers suggested in a series of studies presented here at the annual meeting.

In one study with 4 years of follow-up, regular users of non-steroidal anti-inflammatory drugs (NSAIDs) for moderate to severe osteoarthritis of the knee showed significantly greater 3T MRI signal intensities, indicating worsening osteoarthritis, compared with individuals who used NSAIDs episodically, reported Johanna Luitjens, MD, a postdoctoral scholar in radiology at the University of California San Francisco (UCSF).

In a second study, Azad Darbandi, MS, a medical student/researcher at the Chicago Medical School of Rosalind Franklin University of Medicine and Science, reported that when patients were randomized to receive steroid injections, injections of hyaluronic acid, or no treatment, after 2 years of observation a key marker of knee health -- medial joint space narrowing -- worsened significantly among those getting steroids compared with controls. There was no statistically significant difference in that marker between patients getting hyaluronic acid injections and controls.

And in a third study, which also compared steroids, hyaluronic acid injections, and matched control subjects who received no treatment, the results again showed worsening with steroids after 2 years of follow-up, reported Upasana Upadhyay Bharadwaj, MBBS, a postdoctoral scholar in the Department of Radiology and Biomedical Imaging at UCSF.

Luca Sconfienza, MD, PhD, head of the Unit of Diagnostic and Interventional Radiology at the University of Milan in Italy, told MedPage Today: "We have been aware of this situation in the medical literature -- that steroids may have long-term harm, but these studies confirm this with higher evidence."

"The reason for steroids to be potentially dangerous for the joint is twofold," said Sconfienza, who was not involved with the study. "On the one hand, the steroids may directly damage the joint by weakening the bone which is under the cartilage. The second thing is that steroids are very powerful as painkillers, and therefore after an injection the patient doesn't feel pain anymore and then can resume their activity even though the joint is not perfect. This can further progress the damage."

He also noted that the formulations of the steroids used in injections can remain in the joint for long periods of time, and may attach to crystals and deposit them inside the cartilage. Sconfienza said that steroids may be useful in controlling pain in cases where patients are scheduled to undergo procedures for knee prostheses with a relatively short period of time.

"Hyaluronic acid injections don't do this, because what the injections are doing is to supplement hyaluronic acid in the body. Hyaluronic acid improves the nutrition of the cartilage by hydrating the joint," he explained. "The viscous fluid also helps to lubricate the joint, and it has a mechanical effect -- it acts like a shock absorber, and it also induces the body to produce endogenous hyaluronic acid. Hyaluronic acid cannot heal damage to the joints, but it may be able to slow the damage and preserve what has not been damaged."

NSAIDs

In the study presented by Luitjens, 277 participants from the Osteoarthritis Initiative (OAI) cohort taking NSAIDs were compared with 793 control participants who were not treated with NSAIDs. Both groups underwent 3T MRI of the knee initially and after 4 years. Images were scored for biomarkers of inflammation.

OAI is a multicenter, longitudinal, observational study of nearly 5,000 participants with knee osteoarthritis currently in its 14th year of follow-up.

The results showed no long-term benefit of NSAID use, Luitjens reported. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up, she said.

"On the one hand, the anti-inflammatory effect that normally comes from NSAIDs may not effectively prevent synovitis, with progressive degenerative change resulting in worsening of synovitis over time," Luitjens noted in her presentation. "On the other hand, patients who have synovitis and are taking pain-relieving medications may be physically more active due to pain relief, which could potentially lead to worsening of synovitis, although we adjusted for physical activity in our model."

Sconfienza noted that while NSAIDs do not have a direct effect on the joint, they do have the ability to relieve pain, so like with steroid injections, patients may continue activities and worsen their condition.

Steroid Injections

Darbandi and colleagues also selected patients from the OAI database, enrolling 50 patients who received corticosteroid injections, 50 who received hyaluronic acid injections, and 50 who were not injected over a 36-month time period. The groups were matched by sex, body mass index (BMI), and x-ray findings.

Patients underwent x-ray imaging of the knee at baseline and 2 years later. The researchers analyzed the images, including joint space narrowing, formation of bone spurs, and bone thickening around the knee cartilage.

"Even though imaging findings for all patients were similar at baseline, the imaging hallmarks of osteoarthritis were worse 2 years later in patients who received corticosteroid injections compared to patients who received hyaluronic acid injections or no treatment at all," Darbandi said. "The results suggest that hyaluronic acid injections should be further explored for the management of knee osteoarthritis symptoms, and that steroid injections should be utilized with more caution."

Upadhyay Bharadwaj also accessed patients from the OAI. Her team's study included 210 patients; 44 were injected with corticosteroids, and 26 with hyaluronic acid. The treatment and control groups were matched by age, sex, BMI, pain and physical activity scores, and severity of disease.

MRI was performed on all patients at the time of the injection and 2 years before and after. Corticosteroid knee injections were significantly associated with the overall progression of osteoarthritis in the knee, specifically in the lateral meniscus, lateral cartilage, and medial cartilage, Upadhyay Bharadwaj reported.

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