Trajectory and predictors of cartilage damage in three compartments of the knees at risk for osteoarthritis

To the Editor: Osteoarthritis (OA) is a prominent disabling disease characterized by progressive articular cartilage damage coupled with deterioration in the subchondral bone and other structures of the joint, and is ranked as the 12th highest disease contributing to global disability.[1] The course of knee OA is considerably long and can affect three knee compartments (the patellofemoral joint [PFJ], medial tibiofemoral joint [MTFJ], and lateral tibiofemoral joint [LTFJ]) alone or in combination, resulting in a large variation in the occurrence of cartilage damage in the three compartments.[2] We aimed to determine the baseline predictors associated with distinct tricompartmental trajectories of cartilage damage in knees at risk for OA. This study drew on de-identified and anonymous data from the osteoarthritis initiative (OAI). A total of 923 knees from 855 participants with Kellgren–Lawrence (KL) grades of 0–1 at baseline were selected. An acknowledged group-based trajectory modelling was used to identify tricompartmental trajectories of cartilage damage in this study. The magnetic resonance imaging (MRI, Trio, Siemens Medical Solutions, Erlangen, Germany) scan results of baseline and first, second, third, and fourth year of follow-up were assessed.[3] The MRI Osteoarthritis Knee Score, based on a strict multi-subregional and semi-quantitative scoring system, was used to assess OA-related features of the three compartments of the knee. We categorized the participants into three groups (one-compartment, two-compartment, and three-compartment groups) according to the number of knee compartments involved. Ethics approval was obtained by the OAI project (registry number: NCT00080171). Informed consent was obtained from all individual participants. Multinomial logistic regression was used to evaluate the associations between the baseline characteristics and subgroups. Based on previous evidence of potential determinants of structural progression of OA,[4] the following baseline characteristics were selected to investigate their associations with tricompartmental trajectories of cartilage damage: age, obesity (body mass index ≥ 30 kg/m2), knee pain (assessed by the Western Ontario & McMaster Universities Osteoarthritis Index pain score, 0–20), duration of knee pain, KL grade at baseline, medial joint space narrowing score at baseline, baseline alignment (type based on physical examination, and femorotibial angle based on knee radiography), meniscal tear or extrusion (based on an MRI image), bone marrow lesion (BML, based on an MRI image), patellar grind, and contralateral knee OA (KL grade ≥ 2). All statistical analyses were conducted using Stata version 15.1 (StataCorp, College Station, TX, USA). Six distinct tricompartmental trajectories were identified in the optimal model and divided into three groups according to the number of knee compartments involved [Figure 1]: (1) unicompartmental damage (18.2% [168/923], PFJ; 11.9% [110/923], MTFJ); (2) bicompartmental damage (7.6% [70/923], MTFJ and LTFJ; 24.2% [223/923], PFJ and MTFJ; 18.5% [171/923], PFJ and LTFJ); and (3) tricompartmental damage (19.6% [181/923], PFJ, MTFJ, and LTFJ). Unicompartmental cartilage deterioration showed isolated PFJ damage progression or MTFJ damage progression; bicompartmental cartilage deterioration showed combined damage progression in MTFJ and LTFJ, PFJ and MTFJ, or PFJ and LTFJ; tricompartmental cartilage deterioration involved three cartilage damage progression. The trajectory of cartilage damage in three compartments of the knees was shown in Figure 1. Multinomial logistic regression model results suggest that obese patients had higher risk for developing two-compartment or three-compartment cartilage damage in knees at risk for OA (odd ratio [OR] = 1.74, 95% confidence interval [CI]: [1.13–2.68], P = 0.013; OR = 1.73, 95% CI: [1.05–2.86], P = 0.038). The odds of having two compartments or three compartments involved increased for every 1-year increase in age (OR = 1.02, 95% CI: [1.01–1.03], P = 0.042; OR = 1.05, 95% CI: [1.02–1.08], P = 0.004). Patients with medial meniscal extrusion had more than 1.6 times odds of being in the three-compartment group and two-compartment group compared with patients without medial meniscal extrusion. Patients with lateral meniscal tears had more than 2.7 times odds of being in the two-compartment group or three-compartment group compared with the patients without lateral meniscal tears. Knee valgus or varus was associated with decreased risk for the three-compartment involvement, but the BML at baseline was associated with increased risk for the three-compartment involvement [Supplementary Table 1, https://links.lww.com/CM9/B194].Figure 1: The pattern diagrams and trajectories of cartilage damage progression in the PFJ, MTFJ, and LTFJ compartments of the knee over four years. (A) The trajectories of cartilage damage progression in unicompartmental cartilage deterioration of the PFJ. (B) The trajectories of cartilage damage progression in unicompartmental cartilage deterioration of the MTFJ. (C) The trajectories of cartilage damage progression in bicompartmental cartilage deterioration of MTFJ and LTFJ. (D) The trajectories of cartilage damage progression in bicompartmental cartilage deterioration of MTFJ and PFJ. (E) The trajectories of cartilage damage progression in bicompartmental cartilage deterioration of PFJ and LTFJ. (F) The trajectories of cartilage damage progression in tricompartmental cartilage deterioration. LTFJ: Lateral tibiofemoral joint; MTFJ: Medial tibiofemoral joint; PFJ: Patellofemoral joint.A few previous studies, which divided the knee into two compartments (the PFJ and tibiofemoral joint), have reported the changes in the compartment distribution of structural damage over time, and used different definitions of damage such as the KL grade (≥2) or the semiquantitative Whole-Organ MRI Score (≥2) of cartilage lesions.[5] In contrast with these studies, we first used a data-driven approach to classify subjects with similar cartilage deterioration into the three compartments of the knee with OA risk, which could lead to insights into the interplay among the three compartments of the knee. Whether the cartilage structural integrity, mechanical integrity, and disease process of the LTFJ compartment of the knees will be affected by MTFJ cartilage damage has been debating. The distinct trajectories of MTFJ and LTFJ deterioration revealed that isolated LTFJ cartilage deterioration was rare (less than 5% in the previous meta-analysis reported)[6]; LTFJ cartilage damage is often accompanied by MTFJ and/or PFJ damage. Therefore, we may speculate that the LTFJ is a unique unit in the knee cavity and the structural lesions on it is always accompanied by the damage of MTFJ and/or PFJ compartment. In addition, we found that the three-compartment group had a lower proportion of valgus or varus knees than the one-compartment group. The reason might be that varus/valgus alignment has a role in protecting the cartilage of the LTFJ/MTFJ compartment. In summary, bicompartmental cartilage damage is more common than unicompartmental and tricompartmental cartilage damage, and age, obesity, lateral meniscal tears, and medial meniscus extrusion may lead to an increasing number of involved knee compartments. These findings are significant for clinicians and researchers to understand the disease process of structural damage in the different compartments and develop targeted therapies for the compartments of knees at risk for OA. Funding This study was funded by the National Natural Science Foundation of China (No. 81974347), National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (No. Z20191008), and Science and Technology Foundation of Sichuan Province of China (No. 2021YFH0094). Conflicts of interest None.

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