In this cross-sectional study of 633 subjects from the OAI we have assessed the presence, location, type and size of dABs within the femorotibial joint. 39% Of the participants were found to display dABs, the majority of those being internal osteophytes. The tibiae were more frequently affected by dAB than the weight-bearing portion of the femoral condyles, and the lateral femorotibial compartment more often than the medial. However, when only considering full thickness cartilage loss, the medial compartment had a more frequent involvement than the lateral one, and cMF had the largest relative area of cartilage loss. To our surprise, the central subregions were not the main location of dABs in any of the cartilage plates as determined by the 10% threshold used in this study. A potential explanation is that because 60% of all dABs were internal osteophytes, the central locations may be less involved due to continuous mechanical loading of these areas. dABs were more frequent in men, and there was a statistically significant, albeit not clinically relevant, relationship with increasing age and BMI. As expected, there was a strong relationship between the presence of dAB and advanced radiographic disease stages, i.e., cKL grade and JSN in the same compartment. In all plates but cLF, there was also a strong correlation between the size of dAB and increasing cKL grades.
Denuded area of subchondral bone (dAB) is a term derived from morphometry where measurements of cartilage are quantified from MR images, dAB representing an area where the subchondral bone is not covered by cartilage1
. Thus, dAB represents an area where the ThC is 0 mm and that could hence represent either full thickness cartilage loss or internal osteophytes. To our knowledge there are no comprehensive reports on the numbers of internal osteophytes in OA subjects by MRI or arthroscopy, and comparative studies between MRI and arthroscopy have so far focussed on focal cartilage lesions/defect24,25
, but not on dABs in general. Further, none of the semi-quantitative methods currently in use to assess knee OA on MR images assesses internal osteophytes26,27
. Therefore, dABs remain an MRI finding and need to be further assessed in the context of their clinical relevance.
Recent studies have shown a significant relationship between dABs and the presence and incidence of pain8
as well as between dABs and the rate of progression of cartilage loss9
. A recent paper in a small cohort of 61 participants with medial femorotibial OA, where one knee per subject was studied, showed that about a third of the participants displayed a dAB in both the medial and the lateral femorotibial compartment, and that dABs were more frequent amongst KL grade 3 than two participants28
. However, little is known about the location, type and size of dABs in the femorotibial joint of participants with medial or lateral disease, and their relation with the entire spectrum of radiographic stages of OA. We therefore performed a comprehensive and descriptive study on regional distribution patterns of dABs in a large sample from the OAI and investigated their relationship with radiographic OA stages.
A limitation of the current study is that only the weight-bearing part of the femoral condyles was assessed in a region of interest covering 60% of the distance between the intercondylar notch and the posterior end of the femoral condyles21
, but did not take into account the patella, femoral trochlea or posterior parts of the femoral condyles. However, these other regions cannot be reliably measured on coronal views. We have given preference to the selection of the coronal FLASHwe in this study, as it has been specifically validated not only for measuring cartilage volume and thickness, but also for the purpose of measuring cAB and dAB23
. Moreover, recent MRI-based studies have shown that the weight-bearing regions of the femoral condyles are more frequently affected by cartilage loss than the posterior regions10,29
. Another limitation was that the cohort was not specifically selected for the purpose of the study question. However, we obtained a sample spanning from healthy knees to severe radiographic OA stages although few participants were cKL grades 0, 1 and 4. Nevertheless, it was interesting to note that despite the uncertainty in assigning a KL 0 grade (no osteophyte) or a KL 1 grade (possible or minute osteophyte) to a knee, those with cKL grade 1 had substantially more dABs than those with cKL grade 0.
In all cartilage plates, internal osteophytes were more commonly seen than actual cartilage loss in cKL grade 2 or 3 knees, whereas cartilage loss was more commonly seen (than internal osteophytes) in cKL grade 4 knees of all plates but LT. This supports the assumption that osteophytes precede cartilage loss, but the natural history of both cartilage loss and osteophytes (including internal osteophytes) needs to be confirmed in longitudinal trials. The external subregion was the most commonly affected subregion on the medial side, where a majority of the dABs represented full thickness cartilage loss (data not shown). On the lateral side, however, the internal- (cLF) and posterior subregion (LT) was most commonly affected by dAB, and in these two subregions dABs most frequently represented internal osteophytes (data not shown).
Since dABs represent a calcified surface (either from internal osteophyte or from missing cartilage), it is plausible to assume that they interfere with load transmission under both static (lack of hydrostatic pressurization) and dynamic conditions (i.e., increased friction), especially when located in the weight-bearing area (i.e., central subregion). Unlike the articular cartilage, the subchondral bone is highly innervated by pain receptors, and focal exposure of subchondral bone is thus likely to produce pain30
. In support, a recent publication showed a significant relationship between the presence of dABs in OA subjects and the presence and incidence of pain8
. In the current study we show that only a minority of the dABs affected central subregions of the femorotibial cartilage plates. Future studies may therefore investigate whether the relationship between dABs and pain becomes stronger when only considering those cases with centrally located dABs, where the highest pressure can be assumed to occur during normal daily activities. Further, only 40% of all dABs represented actual exposure of subchondral bone (i.e., full thickness cartilage loss). We are not aware of studies investigating whether internal osteophytes are or are not innervated with pain receptors or whether they form prior to or after some kind of cartilage lesion. Therefore, it would also be of interest to further investigate relationship of full thickness cartilage loss dABs and internal osteophyte dABs with pain, respectively.
In conclusion, this paper shows that dABs occur already at the earliest stages of radiographic OA and that they become more common with increasing disease severity. The lateral femorotibial compartment was more often affected by “any dAB” than the medial one, this because of the high frequency of internal osteophytes, particularly located in the internal part of the lateral femoral condyle and in the posterior part of the LT. When considering full thickness cartilage loss only, the medial compartment, however, had a more frequent involvement than the lateral one, the external tibia and femur being more frequently affected than other medial subregions. Presence and size of dABs was related to radiographic disease stages, i.e., increasing cKL grade and JSN were in the same compartment as the dAB. Almost all KL grade 4 knees exhibited dABs, with cartilage loss being more frequent than internal osteophytes.