Purpose: Early diagnosis and intervention for knee osteoarthritis (OA) are important. The prevalence of abnormalities detected on magnetic resonance imaging (MRI), such as bone marrow lesions, meniscal lesions, and synovitis, were higher in the knees with early knee OA (EKOA) than those with normal knees. Among these abnormalities, synovitis has been reported to be a trigger of cartilage degeneration. The purpose of this study was to investigate the influence of synovitis on progression of knee OA in participants without radiographic abnormalities. It was hypothesized that the presence of synovitis would be demonstrated in knees with EKOA, and that synovitis would be correlate with progression of knee OA.
Methods: Subjects were voluntary participants from the Iwaki Health Promotion Project of 2016 and 2019. We excluded participants whose radiograph showed radiographic knee OA (KL grade ≥ 2) at baseline, whose ultrasonography (US) data was incomplete. Finally, a total of 404 participants were included in this analysis. EKOA was defined according to the international criteria based on the knee injury and OA outcome scales (KOOS), joint line tenderness, and crepitation. Participants were classified into non-OA (i.e. without EKOA) and EKOA group. Furthermore, to investigate an influence of obesity on progression of knee OA, participants with overweight was defined as those with a BMI of 25 or higher. Synovitis was quantified by the effusion area (mm2) at the echo-free space of the suprapatellar pouch detected by US. At 3-year follow-up, we defined knees with KL grade of 0 or 1 as the non-progressors, and knees with radiographic knee OA as the progressors. In addition, we assessed the effusion volume (cm3) using MRI to confirm the US data. 255 womenwithout radiographic abnormalities were randomly enrolled and performed MRI. Receiver operating characteristic (ROC) analysis and logistic regression analysis were performed to investigate the influence of the effusion area on progression of knee OA.
Results: Fifty-five of 404 participants (14%) were classified into the EKOA group at baseline, and its prevalence were 10% in men and 21% in women. The overall mean age was 50.7 ± 13.3 years, and the mean BMI was 22.7 ± 3.1 kg/m2 at baseline. The mean values of the effusion area detected by ultrasonography in the non-OA and EKOA groups were 39.9 ± 34.2 and 54.6 ± 39.5 mm2 in men (p=0.048), and 31.2 ± 30.8 and 50.9 ± 48.1 mm2 in women (p=0.002), respectively.
Table 1Clinical characteristics of participants
| Male | Female | |||||
|---|---|---|---|---|---|---|
| Non-OA | EKOA | p-value | Non-OA | EKOA | p-value | |
| Age | 50.6±13.9 | 55.7±14.1 | 0.118 | 49.8±13.1 | 53.7±10.8 | 0.039 |
| BMI | 23.5±2.8 | 24.6±2.3 | 0.092 | 21.7±2.8 | 23.4±4.6 | 0.027 |
| KOOS | ||||||
| Symptom | 96.2±4.7 | 73.9±16.2 | <0.001 | 95.5±5.1 | 78.5±14.2 | 0.001 |
| Pain | 97.9±4.3 | 75.8±11.8 | <0.001 | 97.8±4.0 | 75.4±14. | 0.001 |
| Function | 99.5±1.3 | 87.9±17.4 | <0.001 | 99.3±1.8 | 88.1±12.4 | 0.001 |
| QOL | 94.5±9.1 | 55.9±17.4 | <0.001 | 90.7±13.1 | 57.9±15.7 | 0.001 |
| KLG 0, n (%) | 130 (78) | 14 (82) | 0.725 | 135 (73 | 25 (66) | 0.343 |
| Effusion- area (mm2) | 39.9±34.2 | 54.6±39.5 | 0.048 | 31.2±30.8 | 50.9±48.1 | 0.002 |
ROC analysis showed that the optimal effusion area cut-off value to diagnose EKOA was 29 mm2 (AUC = 0.587; odds ratio: 2.92; p = 0.025) in women.
The sensitivity was 63%, and specificity was 63%. We could not detect the optimal cut-off value of effusion area in men (p=0.154). In MRI analysis, the effusion volume and synovitis showed higher in the EKOA group than those in the Non-OA group.
The number of non-progressors and progressors were shown in Table 2.
Table 2Knee OA in participants by non-OA and EKOA at baseline, and changes over 3 years
| Baseline | Total | Male | Female | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Non-progressors | Progressors | p-value | Non-OA | EKOA | RKOA | Non-OA | EKOA | RKOA | |
| Non-OA | 235 (60%) | 114 (40%) | 0.003 | 124 (75%) | 4 (2%) | 37 (23%) | 100 (54%) | 7 (4%) | 77 (42%) |
| EKOA | 23 (42%) | 32 (58%) | 7 (41%) | 3 (18%) | 7 (41%) | 11 (29%) | 2 (5%) | 25 (66%) | |
The fraction of progressors was significantly higher in the EKOA groups than those in the Non-OA groups (p=0.003). Next, we compared the effusion area between non-progressors and progressors in the Non-OA and EKOA groups. Progressors tended to show greater effusion area, but there was only significant difference between progressors in the female EKOA and non-progressors in the female Non-OA groups (p=0.006)
Logistic regression analysis showed that women (β=0.60, p<0.001), EKOA (β=0.60, p=0.009), BMI (β=0.10, p=0.002) and effusion area (β=0.01, p=0.008) were significantly correlated with progression of knee OA.
Table 3Examination of factors related to the progression of knee OA in male participan
| Parameter | Univariate crude | Multivariate adjusted (stepwise) | ||||||
|---|---|---|---|---|---|---|---|---|
| Β | p | OR | 95% CI | β | p | OR | 95% CI | |
| Female | 0.49 | <0.001 | 2.67 | 0.27 - 0.71 | 0.60 | <0.001 | 3.36 | 0.37 - 0.84 |
| BMI | 0.05 | 0.098 | 3.70 | -0.01- 0.12 | 0.10 | 0.027 | 2.15 | 0.03 - 0.18 |
| Effusion area | 0.01 | 0.012 | 10.4 | 0.00 - 0.01 | 0.01 | 0.008 | 3.25 | 0.00 - 0.02 |
| EKOA | 0.52 | <0.001 | 2.86 | 0.23 - 0.82 | 0.60 | 0.009 | 2.02 | 0.04 - 0.67 |
Based on the results of logistic regression analysis, ROC analysis was performed to detect the optimal cut-off value of effusion area to predict the progressors in female participants with and without overweight. The cut-off value of effusion area was 31 mm 2 (AUC = 0.691; odds ratio: 6.00; p = 0.029) in women overweight.
Conclusions: Higher effusion area measured by US and higher BMI at baseline were the risk factors for progression of knee OA in those with EKOA patients. Synovitis might be a target for the prevention of knee OA at an early stage.
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