Within-subregion relationship between bone marrow lesions and subsequent cartilage loss in knee osteoarthritis.

OBJECTIVE: Bone marrow lesions are believed to increase risk of knee osteoarthritis (OA) progression. Whether their effect is local and whether it can be explained by other types of bone lesions concomitantly present in the same subregion is unclear. We evaluated bone lesion frequency in subregions without cartilage lesions and cartilage lesion frequency in subregions without bone lesions, and investigated the within-subregion bone marrow lesion/subsequent cartilage loss relationship after adjusting for other types of bone lesions at baseline. METHODS: Individuals with knee OA had magnetic resonance imaging at baseline and 2 years later. Cartilage integrity and bone marrow lesions, cysts, and attrition were scored within tibiofemoral subregions. Logistic regression, with generalized estimating equations to account for correlation among multiple subregions within a knee, was used to estimate odds ratios (ORs) for cartilage loss associated with bone marrow lesions, adjusting for age, sex, body mass index, and bone attrition and cysts in the same subregion. RESULTS: Analyzing 1,953 subregions among 177 knees, 90% of subregions had no bone lesions at baseline. Only 0-3% of subregions without cartilage lesions had bone lesions in the same subregion; in contrast, 5-33% of subregions without bone lesions had cartilage lesions. Bone marrow lesions at baseline were associated with cartilage loss in the same subregion at 2 years, adjusting for other types of bone lesions at baseline (adjusted OR 3.74, 95% confidence interval 1.59-8.82). CONCLUSION: In subjects with knee OA, bone marrow lesions were rare at early disease stages but predicted subregional cartilage loss after accounting for the presence of other types of bone lesions in the same subregion.

Medial-to-lateral ratio of tibiofemoral subchondral bone area is adapted to alignment and mechanical load.

Malalignment is known to affect the medial-to-lateral load distribution in the tibiofemoral joint. In this longitudinal study, we test the hypothesis that subchondral bone surface areas functionally adapt to the load distribution in malaligned knees. Alignment (hip-knee-ankle angle) was measured from full limb films in 174 participants with knee osteoarthritis. Coronal magnetic resonance images were acquired at baseline and 26.6 +/- 5.4 months later. The subchondral bone surface area of the weight-bearing tibiofemoral cartilages was segmented, with readers blinded to the order of acquisition. The size of the subchondral bone surface areas was computed after triangulation by proprietary software. The hip-knee-ankle angle showed a significant correlation with the tibial (r (2) = 0.25, P < 0.0001) and femoral (r (2) = 0.07, P < 0.001) ratio of medial-to-lateral subchondral bone surface area. In the tibia, the ratio was significantly different between varus (1.28:1), neutral (1.18:1), and valgus (1.13:1) knees (analysis of variance [ANOVA]; P < 0.00001). Similar observations were made in the weight-bearing femur (0.94:1 in neutral, 0.97.1 in varus, 0.91:1 in valgus knees; ANOVA P = 0.018). The annualized longitudinal increase in subchondral bone surface area was significant (P < 0.05) in the medial tibia (+0.13%), medial femur (+0.26%), and lateral tibia (+0.19%). In the medial femur, the change between baseline and follow-up was significantly different (ANOVA; P = 0.020) between neutral, varus, and valgus knees, with the increase in surface area being significantly greater (P = 0.019) in varus than in neutral knees. Tibiofemoral subchondral bone surface areas are shown to be functionally adapted to the medial-to-lateral load distribution. The longitudinal findings indicate that this adaptational process may continue to take place at advanced age.

Patterns of femorotibial cartilage loss in knees with neutral, varus, and valgus alignment.

OBJECTIVE: Malalignment is known to alter medial-to-lateral femorotibial load distribution and to affect osteoarthritis (OA) progression in the mechanically stressed compartment. We investigated the pattern of cartilage loss in neutral, varus, and valgus knees. METHODS: Alignment was measured from full-limb radiographs in 174 participants with symptomatic knee OA. Coronal magnetic resonance images were acquired at baseline and a mean +/- SD of 26.6 +/- 5.4 months later. The weight-bearing femorotibial cartilages were segmented from paired images. Cartilage volume, surface area, and thickness were determined in total cartilage plates and defined subregions using proprietary software. RESULTS: The medial-to-lateral ratio of femorotibial cartilage loss was 1.4:1 in neutral knees (n = 74), 3.7:1 in varus knees (n = 57), and 1:6.0 in valgus knees (n = 43). The relative contribution of cartilage thickness change tended to be greater in knees with mild cartilage loss, whereas the increase of denuded area was greater in knees with accelerated cartilage loss. In both varus and neutral knees, the greatest changes were observed in the same subregions of the medial femorotibial compartment (central and external medial tibia, and central medial femur). In valgus and neutral knees, the subregions with the greatest changes in the lateral femorotibial compartment were also similar (internal and central lateral tibia, external lateral femur). CONCLUSION: The medial-to-lateral rate of femorotibial cartilage loss strongly depended on alignment. Subregions of greater-than-average cartilage loss within the stressed compartment were, however, similar in neutral, varus, and valgus knees. This indicates that the medial-to-lateral loading pattern is different, but that the (sub)regional loading pattern may not differ substantially between neutral and malaligned knees.

Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees.

OBJECTIVE: Progressive knee osteoarthritis (OA) is believed to result from local factors acting in a systemic environment. Previous studies have not examined these factors concomitantly or compared quantitative and qualitative cartilage loss outcomes. The aim of this study was to test whether meniscal damage, meniscal extrusion, malalignment, and laxity each predicted tibiofemoral cartilage loss after controlling for the other factors. METHODS: Laxity and alignment were measured at baseline in individuals with knee OA. Magnetic resonance imaging included spin-echo coronal and sagittal imaging for meniscal scoring and axial and coronal spoiled gradient echo sequences with water excitation for cartilage quantification. Tibial and weight-bearing femoral condylar subchondral bone area and cartilage surface were segmented. Cartilage volume, denuded bone area, and cartilage thickness were quantified in each plate, with progression defined as cartilage loss >2 times the coefficient of variation for each plate. Qualitative outcome was assessed as worsening of the cartilage score. Logistic regression analysis with generalized estimating equations yielded odds ratios for each factor, adjusting for age, sex, body mass index, and the other factors. RESULTS: We studied 251 knees in 153 persons. After full adjustment, medial meniscal damage predicted medial tibial cartilage volume loss and tibial and femoral denuded bone increase, while varus malalignment predicted medial tibial cartilage volume and thickness loss and tibial and femoral denuded bone increase. Lateral meniscal damage predicted every lateral outcome. Laxity and meniscal extrusion had inconsistent effects. After full adjustment, no factor except medial laxity predicted qualitative outcome. CONCLUSION: Using quantitative cartilage loss assessment, local factors that independently predicted tibial and femoral loss included medial meniscal damage and varus malalignment (medially) and lateral meniscal damage (laterally). A measurement of quantitative outcome was more sensitive at revealing these relationships than a qualitative approach.

Full-limb and knee radiography assessments of varus-valgus alignment and their relationship to osteoarthritis disease features by magnetic resonance imaging.

OBJECTIVE: To examine the correlation between hip-knee-ankle and femur-tibia radiograph angles, calculate the offset of the femur-tibia angle with respect to the hip-knee-ankle angle, calculate the sensitivity and specificity and area under the receiver operating characteristic (ROC) curve of the femur-tibia angle, and examine the relationship of malalignment by each approach with osteoarthritis (OA) tissue pathology in the mechanically stressed compartment using magnetic resonance imaging (MRI). METHODS: Individuals with knee OA underwent full-limb and knee radiographs and knee MRI. Linear regression was used to determine if the 2 angles differed systematically and to identify the cutoff. Alignment means for MRI grades were compared using Dunnett's t-test. RESULTS: In the 146 participants (109 women, mean age 70 years, body mass index 30.6 kg/m(2)), femur-tibia and hip-knee-ankle angles correlated (r = 0.86; 95% confidence interval [95% CI] 0.81, 0.90). On average, the femur-tibia angle was 3.4 degrees more valgus (3.0 degrees in women and 4.7 degrees in men); after correction, its sensitivity and specificity (to predict the hip-knee-ankle angle) were 0.84 and 0.84 for identifying varus and 0.98 and 0.73 for valgus, respectively. The area under the ROC curve (95% CI) was 0.91 (0.86, 0.96) for varus and 0.94 (0.89, 0.99) for valgus. Varus severity worsened comparably with each alignment measure as medial lesion score on MRI worsened. Laterally, as lesion score worsened, comparably worse valgus was seen with either assessment approach. CONCLUSION: In knee OA, the knee radiograph femur-tibia and full-limb radiograph hip-knee-ankle angles were correlated. The femur-tibia angle, corrected for mean offset, was sensitive, specific, and had excellent discriminative ability for identifying varus and valgus alignment evidenced by area under the ROC curve. The relationship between alignment and specific OA MRI features was comparable with the 2 approaches. Use of the femur-tibia angle, corrected for offset, should be considered in research and clinical settings.