Infrapatellar steroid injections ineffective for easing knee OA pain and inflammation

medwireNews: Injection of glucocorticoids into the infrapatellar fat pad (IPFP) is no better than placebo for relieving pain or effusion synovitis associated with inflammatory osteoarthritis (OA) of the knee, Chinese researchers have found.

In the 12-week GLITTERS randomized controlled trial, both visual analog (VAS) pain scores (range 100 mm) and effusion synovitis measured by magnetic resonance imaging (MRI) decreased to a similar degree among the 30 patients who were treated with IPFP injections and the 30 patients who were given placebo injections.

VAS pain scores were reduced from baseline by a respective 39.3 mm and 31.4 mm, with a nonsignificant –7.9 mm between-group difference. Effusion volumes were reduced by a respective 4.9 mL and 5.4 mL, again with a nonsignificant between group difference of just 0.5 mL.

“The negative finding of this intra-IPFP glucocorticoid injections trial suggests further work is needed to identify effective interventions in patients with inflammatory knee OA,” Changhai Ding (Zhujiang Hospital, Southern Medical University, Guangzhou City, Guangdong) and co-investigators write in JAMA Network Open.

The researchers explain that the rationale for the study was based on the interconnection of the IPFP with the synovium, a key source of inflammatory markers that when released can “result in changes of the cartilage, synovium, and subchondral bone, ultimately accelerating OA progression.”

The GLITTERS trial enrolled patients aged 45 years and older with symptomatic knee OA, as defined by American College of Rheumatology criteria. The mean age of the 38 women and 22 men who were recruited was 65 years.  

The participants had knee pain lasting at least 6 months and a VAS pain score of 40 mm or greater in the week before recruitment. They all had MRI-assessed synovitis, with a Hoffa synovitis score of 1 point or greater, an effusion synovitis score of 1 point or greater, and a total score of at least 3 points.

Ultrasound was used to guide the administration of a glucocorticoid or placebo preparation, given as 1 mL injections at two consecutive sites at the bottom of the IPFP near the synovium.

The glucocorticoid preparation consisted of 1.0 mL of glucocorticoid (which comprised 5.0 mg of betamethasone dipropionate and 2.0 mg of betamethasone sodium phosphate), 0.5 mL of saline, and 0.5 mL of lidocaine. The placebo preparation included 1.5 mL of saline and 0.5 mL of lidocaine.

Concomitantly, an intra-articular injection of 2.5 mL hyaluronic acid was given to both groups. This was to “facilitate patient recruitment and obtain ethical approval,” the researchers note.

They report that one participant in each group experienced an adverse reaction of increased pain in the knee after the injection.

As well as the primary outcomes, a number of secondary outcome measures were evaluated, including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, pain medication use, and quality of life but no significant differences were seen between the treatment and placebo groups.

However, “certain post-hoc outcomes favored glucocorticoid injections,” Ding and team report. This included a significantly greater mean reduction in WOMAC pain score, from an average of 194.7 points at baseline, than with placebo (113.0 vs 66.8 points) and a significantly greater improvement in cartilage defect score (–0.1 vs 0.4 points), from a mean of 11.6 points at baseline.

Thus, they conclude that further investigation of IPFP injection of glucocorticoids in inflammatory knee OA “may be helpful” and suggest that “clinical trials comparing the effects of intra-articular injections and IPFP injections of glucocorticoid on knee pain are needed.”

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JAMA Netw Open 2026; 9: e2549938