Summary Objective The Osteoarthritis Initiative (OAI) is aimed at validating (imaging) biomarkers for monitoring progression of knee OA. Here we analyze regional femorotibial (FT) cartilage thickness ...changes over 1 year using 3 Tesla MRI. Specifically, we tested whether changes in central subregions exceed those in the total cartilage plates. Methods The right knees of a subsample of the OAI progression subcohort ( n = 156, age 60.9 ± 9.9 years) were studied. Fifty-four participants had definite radiographic osteoarthritis (OA) (KLG 2 or 3) and a BMI > 30. Mean and minimal cartilage thickness were determined in subregions of the medial/lateral tibia (MT/LT), and of the medial/lateral weight-bearing femoral condyle (cMF/cLF), after paired (baseline, follow up) segmentation of coronal FLASHwe images with blinding to the order of acquisition. Results The central aspect of cMF displayed a 5.8%/2.8% change in mean thickness in the group of 54/156 participants, respectively, with a standardized response mean (SRM) of −0.47/−0.31, whereas cartilage loss in the total cMF was 4.1%/1.9% (SRM −0.49/−0.30). In the central MT, the rate of change was −1.6%/−0.9% and the SRM −0.29/−0.20, whereas for the entire MT the rate was −1.0%/−0.5% and the SRM −0.21/−0.12. Minimal thickness displayed greater rates of change, but lower SRMs than mean thickness. Conclusions This study shows that the rate of cartilage loss is greater in central subregions than in entire FT cartilage plates. The sensitivity to change in central subregions was higher than for the total cartilage plate in the MT and was similar to the total plate in the medial weight-bearing femur.
To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees ...from subjects with bilaterally radiographically normal knees.
828 radiographically normal knees (Kellgren Lawrence grade KLG 0) from the Osteoarthritis Initiative OAI were studied; 150 case knees displayed definite radiographic knee OA (KLG ≥ 2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA.
Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing JSN), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (−858 μm; 95% confidence interval −1016, −701 μm) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (−634 μm; −673, −596 μm), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (−530 μm, −631, −428 μm). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment.
Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change.
NCT00080171.
Summary Objective To explore whether subregional laminar femorotibial cartilage spin-spin relaxation time (T2) is associated with subsequent radiographic progression and cartilage loss and/or whether ...one-year change in subregional laminar femorotibial cartilage T2 is associated with concurrent progression in knees with established radiographic OA (ROA). Methods In this case-control study, Osteoarthritis Initiative (OAI) knees with medial femorotibial progression were selected based on one-year loss in both quantitative cartilage thickness (MRI) and radiographic JSW. Non-progressor knees were matched by sex, BMI, baseline Kellgren-Lawrence-grade (2/3), and pain. Baseline and 1-year follow-up superficial and deep cartilage T2 was analyzed in 16 femorotibial subregions using multi-echo spin-echo MRI. Results 37 knees showed medial femorotibial progression whereas 37 matched controls had no medial or lateral compartment progression. No statistically significant baseline differences between progressor and non-progressor knees in medial femorotibial cartilage T2 were observed in the superficial (48.9±3.0ms; 95%CI:47.9,49.9 vs. 47.8±3.6ms; 95%CI:46.6,49.0, p=0.07) or deep cartilage layer (40.8±3.6ms; 95%CI:39.5,42.0 vs. 40.1±4.7ms; 95%CI:38.5,41.6, p=0.29). Concurrent T2 change was more pronounced in the deep than the superficial cartilage layer. In the medial femorotibial compartment, longitudinal change was greater in the deep layer of progressor than non-progressor knees (1.8±4.5ms; 95%CI:0.3,3.3 vs. -0.2±1.9ms; 95%CI:-0.8,0.5, p=0.02), whereas no difference was observed in the superficial layer. Conclusion Medial compartment cartilage T2 did not appear to be a strong prognostic factor for subsequent structural progression in the same compartment of knees with established ROA, when appropriately controlling for covariates. Yet, deep layer T2 change in the medial compartment occurred concurrent with medial femorotibial progression.
To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display ...greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees.
120 radiographically normal knees (Kellgren Lawrence grade KLG 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus.
Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m2), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval CI 0.4, 2.0) than in matched KLG0 reference knees (0.1 ms; 95% CI −0.5, 0.7). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment.
Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees.
NCT00080171.
Summary Objective To compare the rate and sensitivity to change of quantitative cartilage thickness change with magnetic resonance imaging (MRI) across specific radiographic strata of knee ...osteoarthritis (KOA) from central expert readings of the Osteoarthritis Initiative (OAI). Specifically, we explored whether Kellgren Lawrence grade (KLG) 2 knees with radiographic joint space narrowing (JSN) displayed greater cartilage loss than those without JSN, and whether knees with medial JSN grade2 had greater loss than those with grade1. Methods One-year femorotibial cartilage thickness change was obtained for 836 knees, 112 without, and 724 with definite radiographic KOA based on baseline site readings. The maximum subregional cartilage loss, and cartilage thickness change in the total femorotibial joint (FTJ) and medial femorotibial compartment (MFTC) were analyzed across different radiographic strata (central vs site readings). Results The maximum subregional rate of change was significantly greater in central_KLG2 knees with than in those without JSN (172 ± 152 vs 134 ± 100 μm; P = 0.03). In contrast, the rate did not differ significantly between central_KLG1 knees with and without JSN. MFTC cartilage loss in central_medial_grade2 JSN knees was substantially and significantly greater than in grade1 knees (−70 ± 159 vs −31 ± 126 μm; P = 0.02). For comparison, the loss in grade3 knees was −72 ± 122 μm. Conclusions In KLG2 knees, presence of radiographic JSN was associated with significantly and substantially greater rates of subregional cartilage loss. Differentiating knees with mild vs moderate medial JSN, and definite radiographic OA knees with vs without JSN is important in predicting structural progression of KOA, and for planning clinical trials testing the efficacy of disease modifying drugs (DMOADs).
Magnetic resonance imaging (MRI)-based spin-spin relaxation time (T2) mapping has been shown to be associated with cartilage matrix composition (hydration, collagen content &orientation). To ...determine the impact of early radiographic knee osteoarthritis (ROA) and ROA risk factors on femorotibial cartilage composition, we studied baseline values and one-year change in superficial and deep cartilage T2 layers in 60 subjects (age 60.6 ± 9.6 y; BMI 27.8 ± 4.8) with definite osteophytes in one knee (earlyROA, n = 32) and with ROA risk factors in the contralateral knee (riskROA, n = 28), and 89 healthy subjects (age 55.0 ± 7.5 y; BMI 24.4 ± 3.1) without signs or risk factors of ROA. Baseline T2 did not differ significantly between earlyROA and riskROA knees in the superficial (48.0 ± 3.5 ms vs. 48.1 ± 3.1 ms) or the deep layer (37.3 ± 2.5 ms vs. 37.3 ± 1.8 ms). However, healthy knees showed significantly lower superficial layer T2 (45.4 ± 2.3 ms) than earlyROA or riskROA knees (p ≤ 0.001) and significantly lower deep layer T2 (35.8 ± 1.8 ms) than riskROA knees (p = 0.006). Significant longitudinal change in T2 (superficial: 0.5 ± 1.4 ms; deep: 0.8 ± 1.3 ms) was only detected in healthy knees. These results do not suggest an association of early ROA (osteophytes) with cartilage composition, as assessed by T2 mapping, whereas cartilage composition was observed to differ between knees with and without ROA risk factors.
Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition ...(transverse relaxation-time T2) are greater in radiographically normal knees “at risk” of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations.
755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade KLG 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were “at risk”, whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n = 59/52). Subregion values were used to compute location-independent change scores.
In KLG0 knees “at risk”, the femorotibial cartilage thinning score (−634 ± 516 μm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p < 0.01; Cohen D −0.27) than the thinning score in “non-exposed” knees (−501 ± 319 μm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p ≥ 0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance.
Knees “at risk” of incident knee OA displayed greater cartilage thinning scores than those “non-exposed”. Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.
The Osteoarthritis Initiative (OAI) is a multicentre study targeted at identifying biomarkers for evaluating the progression and risk factors of symptomatic knee OA. Here cartilage loss using 3 Tesla ...(3 T) MRI is analysed over 1 year in a subset of the OAI, together with its association with various risk factors.
An age- and gender-stratified subsample of the OAI progression subcohort (79 women and 77 men, mean (SD) age 60.9 (9.9) years, body mass index (BMI) 30.3 (4.7)) with both frequent symptoms and radiographic OA in at least one knee was studied. Coronal FLASHwe (fast low angle shot with water excitation) MRIs of the right knee were acquired at 3 T. Seven readers segmented tibial and femoral cartilages blinded to order of acquisition. Segmentations were quality controlled by one expert.
The reduction in mean cartilage thickness (ThC) was greater (p = 0.004) in the medial than in the lateral compartment, greater (p = 0.001) in the medial femur (-1.9%) than in the medial tibia (-0.5%) and greater (p = 0.011) in the lateral tibia (-0.7%) than in the lateral femur (0.1%). Multifactorial analysis of variance did not reveal significant differences in the rate of change in ThC by sex, BMI, symptoms and radiographic knee OA status. Knees with Kellgren-Lawrence grade 2 or 3 and with a BMI >30 tended to display greater changes.
In this sample of the OAI progression subcohort, the greatest, but overall very modest, rate of cartilage loss was observed in the weight-bearing medial femoral condyle. Knees with radiographic OA in obese participants showed trends towards higher rates of change than those of other participants, but these trends did not reach statistical significance.
PDF
