“With an absence of effective, licensed disease-modifying treatments for OA, attention has turned to identifying clinically important targets for clinical trials,” explains Thomas Perry, PhD. “Synovitis, which is present at all stages of knee osteoarthritis (KOA), has shown promise as a potential treatment target. Imaging biomarkers used to evaluate synovitis are likely to play an increasing role in identifying participants for OA clinical trials and assessing treatment efficacy in which synovitis is the treatment target. However, most data from clinical trials have been inconclusive, and there is currently no consensus on the optimal approach for the assessment of synovitis on MRI in KOA.”

For a study published in Rheumatology (Oxford), Dr. Perry and colleagues aimed to examine the relationship between MRI measures of synovitis and knee symptoms in symptomatic KOA. They used data from a randomized, multicenter, placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Knee symptom data were captured at baseline and annually using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). In addition, utilizing contrast-enhanced (CE)-MRI, synovial thickness was measured using semi-quantitative scoring methods, while synovial tissue volume (STV) was assessed as absolute STV (aSTV) and relative to the width of femoral condyle (rSTV). STV of the infrapatellar region was also assessed.

STV Measures May Prove to Be Useful Outcomes

The study team found that whole joint aSTV (0.88, 95% confidence interval [CI]: 0.17, 1.59) and infrapatellar aSTV (5.96, 95% CI: 1.22, 10.7) were positively linked with knee pain. Whole joint rSTV had a stronger association with pain (7.96, 95% CI: 2.60, 13.33) and total scores (5.63, 95% CI: 0.32, 10.94). Even stronger associations were found for infrapatellar rSTV with pain (55.47, 95% CI: 19.99, 90.96), function (38.59, 95% CI: 2.1, 75.07) and total scores (41.64, 95% CI:6.56. 76.72).

“Our findings show that whole-joint and site-specific infrapatellar STV measures on CE-MRI were associated with knee pain, respectively,” Dr. Perry says. “The size of the knee joint appears to be important in the degree of inflammatory response seen, independent of the disease severity, in symptomatic KOA. Relative measures were more strongly associated with knee symptoms, and there was no linear association between synovial thickness and knee symptoms. Therefore, relative measures of STV may prove to be useful outcomes in trials of KOA.”

Link Between Relative Synovitis Volume & Symptoms

The researchers found specific associations between relative synovitis volume and symptoms. “We discovered that whole knee joint STV and site-specific Hoffa’s-synovitis volume were associated with knee pain, respectively,” Dr. Perry says. “However, volumes relative to the size of the femur were more strongly associated with knee symptoms (Table).” Associations between total synovitis thickness severity and symptoms were also observed. “Synovitis measured using established semi-quantitative scoring was not associated with knee symptoms in symptomatic KOA,” he notes. “These data suggest that quantitative measures of STV are more sensitive in detecting a relationship with knee symptoms than semi-quantitative scores.”

Dr. Perry and colleagues acknowledge that the current study was a secondary analysis of a randomized trial and, thus, the study sample reported was relatively small, thereby reducing statistical power and their ability to detect true associations. “A second limitation is the generalizability of our infrapatellar STV measure,” adds Dr. Perry. “There is great variability in the definition of Hoffa’s synovitis. Also, due to the cross-sectional design of our study, we were unable to determine causality. However, while cross-sectional, the precision of our estimates was likely improved with the addition of data across multiple study visits.” While the study team observed a strong, statistically significant relationship between measures of synovitis and knee symptoms, they cannot completely exclude the contribution of other structural features to knee symptoms, Dr. Perry notes. “Further work is required to confirm these findings using larger observational and/or clinical datasets and to determine measurement error of relative values of STV.”