Synovitis mediates cartilage outcomes during weight-loss in knee osteoarthritis - 4-year follow-up data from the Osteoarthritis Initiative

Abstract

Objective: Weight loss can modify the progression of osteoarthritis (OA), and this may, in part, be achieved by decreased synovitis, a known accelerator of cartilage degeneration. The purpose of this study was to investigate whether change in synovitis mediates the beneficial effect of weight loss on longitudinal cartilage outcomes.

Method: We analyzed right knees with baseline Kellgren & Lawrence grades 1-3 of 1153 obese and overweight participants of the Osteoarthritis Initiative (OAI) cohort with Whole Organ MRI Scores (WORMS) and semi-quantitative assessment of effusion synovitis and synovial proliferation scores form 3T MRIs at baseline and 48 months. There were 295 participants with weight-loss >5 ​% and 858 stable weight controls. Ordered logistic regression was used to assess the association of weight-loss status with concurrent changes in synovitis as well as cartilage WORMS scores; models were adjusted for age, gender, race, presence of radiographic OA, and abdominal circumference at baseline. A mediation analysis was used to determine whether change in overall cartilage degeneration was mediated by change in synovitis scores.

Results: Individuals who lost weight had significantly lower odds for a higher grade on the scale assessing change in overall synovitis (OR 0.72; 95%CI 0.54, 0.95; p ​= ​0.018). Mediation analysis showed that slowing synovitis during weight loss had a small mediating effect on longitudinal cartilage outcomes.

Conclusion: Decreased cartilage degeneration during weight loss was partially mediated by concurrent deceleration in synovitis, showing that decreasing systemic inflammation during weight-loss may not be mirrored in imaging markers of joint inflammation.

Keywords: MRI; Osteoarthritis; Synovitis; Weight-loss.

Fig. 1

Flowchart of patient selection with exclusion criteria and demographics.

Fig. 2

Adjusted mean change in synovitis over 4 years. Mean synovitis scores with change over 4 years. A: Effusion synovitis (difference in slope not statistically significant). B: synovial proliferation, significantly steeper slope in stable weight participants (blue line). C: Sum score of both markers, significantly steeper slope in stable weight participants (blue line). All analyses adjusted for age, sex, gender, race, baseline BMI, baseline abdominal circumference.

Fig. 3

Mediation of weight-loss effects on cartilage by synovitis. Directed acyclic graph (DAG) of mediation analysis. All analyses adjusted for age, sex, gender, race, and baseline abdominal circumference.