Introduction
Menisci distribute the load in the femorotibial joint [
1], have a lubricative function, and are effective in reducing the stress on the articular cartilage during joint mobility [
2]. Meniscal damage and extrusion are common in older individuals, even in those without knee symptoms or radiographic OA [
3]. The cause for the extrusion has been attributed to the disruption of circumferential collagen bundle fibers in the meniscus [
4] and particularly to a posterior root tear [
5].
The menisci are considered of central importance for knee joint health [
6]. Meniscal damage has been suggested to be a local risk factor for structural progression [
7‐
10] and to be associated with subsequent knee replacement [
11]. Surgical removal of the meniscus after injury was reported to be a significant risk factor for developing radiographic OA [
12]. Quantitative (3D) measurement technology of meniscus position and size from MRI [
13] has been shown to be reliable [
14] and to be associated with development of incident radiographic OA [
15], knee pain [
16], and subsequent knee replacement [
11].
Although knees with radiographic joint space narrowing (JSN) have been reported to show less tibial coverage and greater meniscus extrusion than contralateral knees without JSN [
17], no study has yet explored which of the quantitative measures of medial meniscus position and morphology are most strongly related to subsequent structural progression, by comparing these measures in knees with radiographic knee OA with vs. without subsequent structural progression. Further, it has not been studied whether, and if yes to what extent, lateral meniscus measures are related to medial femorotibial progression.
The primary purpose of the current study was to explore whether quantitative measures of medial and/or lateral meniscus position and morphology differ between knees with and without subsequent medial femorotibial progression, and which of the medial or lateral meniscus 3D measures are most strongly associated with structural progression.
A secondary purpose of the study was to explore to what extent quantitative meniscus measures obtained in a central coronal slice, or in the central 5 coronal slices, correlate with those obtained in the entire meniscus, and whether these measures differentiate equally well between progressors and non-progressors. Such central slice measures may be less prone to partial volume effects in the anterior and posterior parts of the meniscus and also require less segmentation time than the analysis of the entire meniscus.
Discussion
In our study, we investigated whether (and which) quantitative measures of medial and lateral meniscus position and morphology differ between knees with and without subsequent medial femorotibial structural progression using a matched study design and explored whether quantitative measures obtained from the center of the meniscus can serve as surrogate for quantitative measures obtained from the entire meniscus. The results from our study identified several (but not all) meniscus position measures to differ between knees with vs. without subsequent medial compartment structural progression, whereas only one of the medial meniscus morphology measures (height) differed between knees with vs. without subsequent progression. Among the lateral meniscus measures, both height and volume differed between progressor than non-progressor knees, with greater values observed in progressor than non-progressor knees. Quantitative measures obtained in the central 5 or the central slice of the medial meniscus were highly correlated with the respective measures obtained from the entire meniscus and the differences between progressor and non-progressor knees were more pronounced for mean extrusion in the central 5 or the central slice than for mean extrusion in the entire medial meniscus.
Meniscus extrusion and damage have been reported to be important risk factors for the development and progression of knee OA, but most of these studies relied on semi-quantitative scorings of meniscus pathology and meniscus extrusion [
29‐
31]. Quantitative 3D measures of meniscus position and morphology have been developed to provide a comprehensive, quantitative picture that not only includes the meniscus position but also the meniscus morphology. The reproducibility of the methodology has been validated and quantitative 3D meniscus measures have been reported to be associated with relevant outcomes such as development of incident radiographic OA [
15] and presence of pain [
16]. More recently, change in meniscus measures has also been shown to be associated with subsequent knee replacement surgery [
11].
The model of accelerated progression used in the current study has been previously used to study differences in thigh muscle cross-sectional areas [
19], thigh adipose tissue [
32], and cartilage T2 [
22]. In contrast to the findings of the current study, none of these previous measures was, however, observed to be a strong predictor of subsequent structural progression. This is despite the tremendous loss in cartilage thickness observed in progressor knees, which even exceeded the loss in knees in the year before knee replacement surgery [
33]. The meniscus, therefore, seems to play a more immediate role for subsequent progression than thigh muscle and adipose tissue and to be more predictive of subsequent structural progression than cartilage T2 measures.
The results from the current study extend findings from previous studies. Bloecker et al. reported a significantly greater extrusion and a significantly reduced tibia plateau coverage in knees with JSN than in contralateral knees without JSN [
17]. Hunter et al. studied the contribution of meniscus extrusion to radiographic JSN using a quantitative 2D methodology and reported change in meniscal position to account for a substantial proportion of change in radiographic JSW [
34]. Later, Roth et al. investigated change in 3D meniscus measures in knees before joint replacement surgery and reported meniscus measures to not only show a significant change but also to provide independent information in explaining the variance of change in radiographic JSW [
35]. Although these studies already suggested meniscus measures to be associated with structural progression measured from radiographs, none of these studies investigated specifically whether quantitative meniscus measures may predict subsequent structural progression and some of these previous studies focused on the direct contribution of meniscus measures to change in radiographic JSW.
The results from the current study showed medial meniscus extrusion to be greater in knees with vs. without subsequent structural progression, indicating a potential role as predictor for subsequent structural progression in knees with radiographic OA. Across the entire meniscus, the difference did, however, only reach statistical significance for the maximum but not the mean extrusion. Knees with subsequent progression also showed a somewhat greater extrusion area and a somewhat reduced tibia plateau coverage when compared to non-progressor knees, but these differences did also not reach statistical significance. This is in line with findings from a previous study investigating the association between meniscus measures and incident radiographic OA [
15], which suggested tibial coverage to be among the least informative measures and to be of less importance than meniscus extrusion. Whether the coverage of the tibia plateau by the meniscus is also comparable between progressor and non-progressor knees under dynamic, weight-bearing conditions is, however, not known, because analyses of the meniscus from MRI are limited to non-weight-bearing conditions.
Medial meniscus height was significantly greater in knees with than in knees without subsequent progression. This may be the consequence of the greater extrusion of the meniscus in progressor than non-progressor knees, because the greater extrusion results in greater parts of the meniscus positioned outside the joint space, where the meniscus shape adapts due to the constraints imposed by the joint capsule and ligaments. Interestingly, also the lateral meniscus height was significantly greater in knees with than in knees without subsequent progression and displayed the greatest effect size between progressor and non-progressor knees. This difference can, however, not be attributed to differences in extrusion, but might be explained by the greater lateral meniscus volume observed in progressor than non-progressor knees. Increased lateral meniscus height or volume should, however, not be considered as direct risk factors for medial compartment progression because the greater values observed in knees with subsequent medial compartment progression could also be due to preceding loss of lateral meniscus substance in knees without subsequent medial compartment progression.
The high correlation observed between meniscus measures obtained from the entire meniscus and from the central slices indicates that restricting the analysis to the center is a suitable replacement for measures obtained from the entire meniscus. Also, while differences in mean medial meniscus extrusion across the entire meniscus did not reach statistical difference between progressor and non-progressor knees, mean medial meniscus extrusion in the central 5 slices or the central slice was greater in progressor knees than non-progressor knees and showed a greater effect size than that observed for mean extrusion across the entire medial meniscus. An analysis of the central slices of the meniscus may, therefore, not only save segmentation time when compared to the analysis of the entire meniscus, but could also improve the sensitivity to differences between groups.
Differences in meniscus extrusion were observed although medial compartment cartilage thickness and radiographic JSW at baseline did not differ between the knees with vs without subsequent progression studied here. The results from the current study, therefore, suggest that quantitatively measured meniscus extrusion may be a valuable predictor for subsequent structural progression. Given the small sample size, the predictive value of meniscus extrusion still needs to be confirmed in larger studies. The association between meniscus extrusion and subsequent cartilage loss is, however, plausible given that the meniscus plays an important role in distributing loads and in balancing the incongruity of the femorotibial cartilages. Meniscus extrusion and damage have also been suggested to be local risk factors for cartilage loss. Chang et al. reported semi-quantitatively scored meniscus tears to be associated with cartilage thickness loss in adjacent cartilage subregions [
7]. More recently, Bloecker et al. reported the effect of meniscus extrusion on cartilage thickness loss to be most pronounced for the external medial tibia subregion, the cartilage subregion most severely affected from medial–lateral extrusion [
36]. Meniscus damage has also been reported to be associated with elevated superficial cartilage T2 relaxation times in adjacent tibial articular cartilage [
37], indicating detrimental alterations in cartilage composition in the affected regions. In the same sample as studied here, we were, however, not able to observe differences in cartilage T2 relaxation times (or change therein) in the external medial cartilage subregion [
22], the subregion most affected from central medial extrusion.
A limitation of the study is the small sample size. This can be attributed to the strict selection criteria that were applied to ensure to only select knees with definite loss in both MRI-based cartilage thickness and radiographic JSW as progressor knees. The sample size was, however, sufficiently large to observe statistically significant results between progressor and non-progressor knees and the combination of MRI and radiography thresholds ensured significant differences in structural progression between progressor and non-progressor knees. Another limitation of the study is that the coronal MRIs did not allow to assess the anterior and posterior extrusion of the menisci due to partial volume effects. Analyzing the anterior and posterior extrusion would have required to analyze sagittal MRIs of the same knees, which would have, in turn, precluded the assessment of extrusion in the body of the meniscus. Another potential limitation of this study is that the quantitative approach used here is not capable of assessing meniscus damage such as tears. These are, however, highly prevalent in knees with radiographic OA as well as in the general population [
3]. Finally, one of the selection criteria (radiographic JSW) was not independent from the meniscus measures, as meniscus extrusion has been reported to contribute to JSN on radiographs [
34,
38].
In conclusion, medial meniscus extrusion was significantly greater in knees with subsequent progression than in knees without subsequent progression while measures of tibia plateau coverage and most measures of medial meniscus morphology differed not significantly between progressor and non-progressor knees. Meniscus extrusion may, therefore, serve as potential predictor of subsequent structural progression in knees with radiographic OA, in particular when focusing on maximum extrusion or measures obtained from the central slice(s) of the meniscus. The high correlation between central meniscus measures and measures obtained from the entire meniscus indicate that central meniscus measures are suitable substitutes of entire meniscus measures that save analysis time and may be even more sensitive to between-group differences.
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