Changes in Cartilage Thickness and Denuded Bone Area after Knee Joint Distraction and High Tibial Osteotomy—Post-Hoc Analyses of Two Randomized Controlled Trials

High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments that unload the more affected compartment (MAC) in knee osteoarthritis. This post-hoc study compares two-year cartilage-thickness changes after treatment with KJD vs. HTO, and identifies factors predicting cartilage restoration. Patients indicated for HTO were randomized to KJD (KJDHTO) or HTO treatment. Patients indicated for total knee arthroplasty received KJD (KJDTKA). Outcomes were the MRI mean MAC cartilage thickness and percentage of denuded bone area (dABp) change two years after treatment, using radiographic joint space width (JSW) as the reference. Cohen’s d was used for between-group effect sizes. Post-treatment, KJDHTO patients (n = 18) did not show significant changes. HTO patients (n = 33) displayed a decrease in MAC cartilage thickness and an increase in dABp, but an increase in JSW. KJDTKA (n = 18) showed an increase in MAC cartilage thickness and JSW, and a decrease in dABp. Osteoarthritis severity was the strongest predictor of cartilage restoration. Kellgren–Lawrence grade ≥3 showed significant restoration (p < 0.01) after KJD; grade ≤2 did not. Effect sizes between severe KJD and HTO patients were large for MAC MRI cartilage thickness (d = 1.09; p = 0.005) and dABp (d = 1.13; p = 0.003), but not radiographic JSW (d = 0.28; p = 0.521). This suggests that in knee osteoarthritis patients with high disease severity, KJD may be more efficient in restoring cartilage thickness.

. Two-year cartilage thickness changes in each of the 16 subregions. Subregions are the central (c), external (e), internal (i), anterior (a) and posterior (p) parts of the tibia (T) and the central, external and internal parts of the femur (F) for both the most (MAC) and least (LAC) affected compartment. KJDHTO = KJD patients from the high tibial osteotomy (HTO) trial; KJDTKA = knee joint distraction (KJD) patients from the total knee arthroplasty trial. Significant two-year changes are indicated with *. Means and standard errors are shown.

Longitudinal changes by patient group: location-independent results
The location-independent cartilage thickening scores were 0.81±0.93 mm for KJDHTO, 0.55±0.48 mm for HTO, and 1.62±0.95 mm for KJDTKA. The thinning scores were −1.14±0.95 for KJDHTO, −1.14±1.48 for HTO, and −0.72±0.69 for KJDTKA. Kruskal-Wallis tests showed no statistically significant difference between the three groups in thinning scores (p = 0.23) but the thickening score was significantly greater for KJDTKA than for the other two groups as confirmed by post-hoc Dunn tests (KJDHTO p = 0.016; HTO p = 0.001). Yet, this was no longer true for the comparison KJDTKA vs KJDHTO when correcting for significantly different baseline characteristics using linear regression (p = 0.505).

Prediction of cartilage thickness changes
A multivariable linear regression model, using patient baseline characteristics and baseline MAC cartilage thickness as independent variables, revealed that only the Kellgren-Lawrence grade was a significant predictor (B = 0.105; p= 0.01) of MAC cartilage thickness change in all KJD and HTO patients together: a higher Kellgren-Lawrence grade was associated with in a greater increase in cartilage thickness during treatment.
Using treatment as independent variable resulted in a better fit of the univariable model (R 2 = 0.120 with p= 0.004 compared to R 2 = 0.095 with p = 0.01), therefore KJD and HTO treated patients were evaluated in separate models as well. For HTO-patients, none of the parameters, including leg axis deviation, significantly predicted the MAC cartilage thickness or JSW change. In contrast, in KJD patients a multivariable linear regression model left only Kellgren-Lawrence grade as a significant predictor for MAC cartilage thickness change.

Supplementary discussion
In KJD patients, the anterior region of the MAC tibia and the central and external regions of the MAC tibia and femur clearly showed the most substantial cartilage restoration. The baseline cartilage thickness in the central femur and external tibia and femur was much smaller than that of the other regions (≥40%; data not shown). This could explain the greater restoration in these three areas. In another MRI cartilage study, the anterior tibial region has been shown to be frequently involved in both thickening and thinning of cartilage [36]. Similarly, in another study, the central tibial and femoral regions showed a greater loss of cartilage than the other regions [37]. As such, the higher rate of cartilage restoration at the central, anterior, and external parts of the MAC may be the result of natural sensitivity to change.