This is the first knee OA study exploring associations between multiple tissue abnormalities, biomechanical factors and physical examination findings. The study provided several clinically relevant findings. Firstly, the clinically relevant and new finding that high-resolution 3.0 Tesla MRI-detected effusion and synovitis, associated with quadriceps weakness. Secondly, several tissue abnormalities (that is, cartilage integrity, osteophytes and effusion), but only when detected by MRI, were found to be associated with the presence of crepitus. Thirdly, we found associations of cartilage integrity with quadriceps weakness and reduced varus-valgus laxity.
The present explorative study showed only a limited amount of significant associations, which indicates discordance between tissue abnormalities and clinical features in knee OA patients. The lack of significant associations between radiographic and clinical features is not surprising, as the discordance between radiographic and clinical OA [13
] is well known and, at least partly, related to the heterogeneity of OA. However, since pain severity has been found to be more closely linked to MRI features than to CR features [47
], we were surprised by the limited amount of significant associations between MRI features, biomechanical factors and physical examination findings.
High-resolution MRI and CR provided similar patterns of association. Firstly, reduced PF cartilage integrity, both MRI based and CR based, was associated with quadriceps weakness, which confirms previous studies [18
]. Secondly, MRI-based and CR-based MTF cartilage integrity loss was related to lower varus-valgus laxity. Although these associations were weak and inconsistent with previous studies [8
], they might be indicative for an ankylosing effect of end-stage cartilage integrity (that is, reduced joint motion due to bone-to-bone) [48
]. Others suggested that cartilage loss results in higher laxity due to reduced tension on ligaments (pseudo-laxity [8
]), which might underlie our finding of reduced LTF cartilage integrity (but only on CR) associated with higher laxity. Future studies are needed to clarify the association between cartilage integrity and laxity. Thirdly, neither features from MRI nor from CR were significantly related to hamstrings strength and proprioceptive accuracy. Finally, no associations were found between tissue abnormalities (MRI and CR) and physical examination findings (except for crepitus), which might, at least partly, be explained by the low proportion of persons with bony enlargement (11%) or palpable warmth (4%) in our cohort. These similar patterns of findings from CR and MRI were determined in a study sample of patients with advanced knee OA with knee complaints for more than 10 years on average. Since MRI is able to detect tissue abnormalities at a much earlier stage of the disease than CR [31
], a different pattern of associations with clinical features may possibly be found in an early OA sample. On the other hand, two results from our study may be indicative for an additional value of MRI over CR. Firstly, MRI-based effusion and synovitis, which cannot be detected by CR, were found to be significantly associated with quadriceps weakness. Secondly, crepitus of the knee was associated with multiple MRI features (that is, LTF cartilage integrity, osteophytes in all three compartments and effusion), similar to a recently conducted population-based study [33
], but was not associated with any feature from CR. This indicates that MRI seems to be able to visualize features underlying crepitus, while CR is not.
A new and potentially important finding from our study is the association of OA-related inflammation (effusion and/or synovitis) with quadriceps weakness, which is in line with previous experimental studies demonstrating an effect of effusion on quadriceps function [49
]. Quadriceps muscles are considered the most important muscles for knee movements, stabilization and shock absorption [11
]. Persons with synovitis and/or effusion had significantly lower quadriceps strength compared with persons without synovitis/effusion. In secondary analyses, similar results were yielded after adjustment for pain severity, indicating that pain does not explain the association between inflammation and quadriceps weakness. Because inflammation of the synovial membrane had mostly been identified in the infrapatellar region (that is, in 86% of persons with synovitis), which is adjacent to the patellar tendon of the quadriceps muscles, it seems plausible that quadriceps function is affected by inflammatory processes nearby the patella. In addition, inflammation may occur inside the muscle as well, which could result in decreased muscle strength [52
]. Effusion is presumed to cause muscle weakness by muscle reflex inhibition due to increased intra-articular pressure [49
]. Although knee joint inflammation has been suggested to also affect proprioceptive accuracy [7
], we were not able to demonstrate this. A possible explanation could be that our study participants demonstrated relatively healthy proprioceptive accuracy. Previous studies provided conflicting results for the role of non-inflammatory effusion (that is, saline injections) in proprioceptive accuracy [53
]. Future studies need to focus on OA-related inflammation, instead of non-inflammatory injections, to clarify the role of inflammation in proprioception.
The associations between effusion, synovitis and quadriceps weakness could be highly relevant for selecting knee OA treatment. If inflammatory processes underlie quadriceps weakness, regular quadriceps strengthening exercises are not likely to be beneficial and anti-inflammatory therapy might be needed first. This implication is in line with a recent study in which patients treated with both NSAIDs and exercises improved more in muscle strength compared with patients treated with exercises only [55
]. In addition, our data revealed that physical examination of the knee strongly underestimated the prevalence of inflammation of the knee, since warmth was palpated in only 4% of our participants, compared with a prevalence of 34% for synovitis and 39% for medium/large effusion, detected by MRI. This implies that MRI may have additional value for clinical assessment in patients with inflammation. Our findings also emphasize that OA is not only characterized by cartilage degeneration and bony changes but also by inflammatory changes, which may point out the importance of anti-inflammatory therapies in knee OA.
Our study design has some limitations that need to be noticed. Firstly, we did not use contrast-enhanced MR imaging techniques to minimize risks for participants (for example, risk of allergic reactions, nephropathy). Because of the well-known superiority of contrast-enhanced MRI for synovitis detection [56
], it is remarkable that even without contrast infusions we were able to detect an association of both effusion and synovitis with quadriceps weakness. Although noncontrast-enhanced MRI demonstrated lower specificity for detecting synovitis compared with contrast-enhanced MRI, meaning that signal intensity alterations do not always represent synovitis, it is also been found to be a highly sensitive technique (≈100% sensitivity) for synovitis detection [57
]. This implies that the prevalence of synovitis in our study could be an overestimation, but that all persons with actual synovitis have presumably been detected. Secondly, we are not sure whether the power of our study was sufficient. Most MRI studies included large cohorts (n
>200), while our study consists of 105 participants. This sample size may have resulted in loss of statistical power. In addition, participants had been selected based on the presence of knee joint instability, since they participated in a study on the effectiveness of a knee stabilization exercise program, which may have introduced selection bias in the present study. Thirdly, our study design was cross-sectional with no control group, while a longitudinal design, preferably using a control group of patients at risk, is necessary to unravel interactions between tissue abnormalities, biomechanical factors and physical examination findings. However, this study has a unique design because it is the first study we are aware of in which associations could be explored between both radiography and MRI with biomechanical and physical examination features in a knee OA cohort.