Which Knee Phenotypes Exhibit the Strongest Correlation With Cartilage Degeneration?
Authors: Khury Farouk , Oltmanns Moritz , Unseld Theresa , Fuchs Michael , Reichel Heiko , Faschingbauer Martin 
Published: September 2023

Abstract

Background
Although articular wear has been thoroughly investigated, the effects of abnormal limb alignment on cartilage degeneration over time remain poorly understood. An exact assessment of the correlation between lower limb alignment abnormalities and MRI-observed articular degradation may be helpful for understanding the progression of osteoarthritis and planning future treatment.

Question/purpose
In patients with moderate to advanced osteoarthritis, (1) is there a correlation between overall alignment of the knee and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? (2) Is there a correlation between tibial alignment and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? (3) Is there a correlation between femoral alignment and the location of cartilage degradation over time, as measured by cartilage metrics on MRI?

Methods
Between April 2020 and September 2022, we retrospectively evaluated 3106 patients aged 45 to 79 years who were at risk of experiencing knee osteoarthritis. Of those, we considered as potentially eligible 600 symptomatic index knees with radiographic evidence of osteoarthritis—Kellgren-Lawrence Grades 2 or 3—at the baseline visit. Of those, 22% (134 of 600) were excluded because of a lack of proper alignment measurements, leaving 466 knees with measurements of radiologic alignment angles and quantitative MRI cartilage measurements of 16 subregions of the femorotibial compartment at baseline and 12 and 24 months, and 64 knees at the 48-month visit for investigation in the current study. Data regarding cartilage measurements of the patellofemoral compartment were not available for analysis. The knees were categorized into one of the possible 25 different phenotypes of the lower extremity established by previous research, based on the neutral, valgus, or varus distal mechanical angle of the femur and proximal tibial mechanical angle on full-limb radiographs. We applied ANOVA to estimate the effect size of the overall, femoral, and tibial alignments on the location of cartilage degradation over time, as measured by cartilage metrics on MRI.

Results
We found that the overall combinations of a valgus femur with valgus tibia or a valgus femur with varus tibia were associated with the highest loss of cartilage in the internal medial tibial subregion and anterior lateral tibial subregion (η2p = 0.39 and 0.17, respectively). For the tibia, we found that the combination of a valgus femur with valgus tibia was associated with an increase in the area of subchondral bone denuded of cartilage in the central lateral tibial subregion (η2p = 0.2). For the femur, we found that the combination of a valgus femur with valgus tibia was associated with loss of cartilage thickness in the central weightbearing lateral femorotibial compartment (η2p = 0.15).

Conclusion
We found that certain alignment patterns are associated with rapid deterioration of cartilage and exposure of subchondral bone, even over short time periods. In particular, the valgus femur with valgus tibia and valgus femur with varus tibia phenotypes deserve special attention, because they exhibited a strong, atypical correlation with the internal medial tibial subregion and anterior lateral tibial subregion, respectively. This is important because valgus and varus malalignment cause isolated lateral and medial compartment disease, respectively. Therefore, these findings suggest that a more individualized approach for limb axis deformities is valuable, and hint at a more meticulous radiologic and clinical investigation, perhaps using different imaging modalities, especially when assessing the exact cartilage state and planning an intervention. Future studies, ideally biomechanical, might help in assessing the long-term effects of the various phenotypes on cartilage degradation and their relevance in reconstructive surgery.

Level of Evidence
Level II, prognostic study.