Dataset Information

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

ABSTRACT: OBJECTIVE: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. METHODS: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. RESULTS: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 ?m; [95% confidence interval -1016, -701 ?m]) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (-634 ?m; [-673, -596 ?m]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (-530 ?m, [-631, -428 ?m]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. CONCLUSIONS: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. CLINICALTRIALS. GOV IDENTIFICATION:NCT00080171.

SUBMITTER: Eckstein F

PROVIDER: S-EPMC7246303 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

Eckstein F F Maschek S S Roemer F W FW Duda G N GN Sharma L L Wirth W W

Osteoarthritis and cartilage 20181028 2

<h4>Objective</h4>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.<h4>Methods</h4>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, an ...[more]

PMID: 30394330

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Project description:To examine whether the quantity of cartilage or semiquantitative scores actually differ in knees with mild radiographic osteoarthritis compared with knees without osteoarthritis.Framingham Osteoarthritis Study participants had knee tibiofemoral magnetic resonance imaging-based measurements of cartilage. Using three-dimensional FLASH-water excitation sequences, cartilage volume, thickness and subregional cartilage thickness were measured and cartilage scored semiquantitatively (using the whole-organ magnetic resonance imaging score; WORMS). Using weight-bearing radiographs, mild osteoarthritis was defined as Kellgren/Lawrence (K/L) grade 2 and non-osteoarthritis as K/L grade 0. Differences between osteoarthritis and non-osteoarthritis knees in median cartilage measurements were tested using the Wilcoxon rank sum test.Among 948 participants (one knee each), neither cartilage volume nor regional thickness were different in mild versus non-osteoarthritis knees. In mild osteoarthritis, cartilage erosions in focal areas were missed when cartilage was quantified over large regions such as the medial tibia. For some but not all subregions of cartilage, especially among men, cartilage thickness was lower (p<0.05) in mild osteoarthritis than non-osteoarthritis knees. Because semiquantitative scores captured focal erosions, median WORMS scores were higher in mild osteoarthritis than non-osteoarthritis (all p<0.05). In moderate/severe osteoarthritis (K/L grades 3 or 4), osteoarthritis knees had much lower cartilage thickness and higher WORMS scores than knees without osteoarthritis.In mild osteoarthritis, the focal loss of cartilage is missed by quantitative measures of cartilage volume or thickness over broad areas. Regional cartilage volume and thickness (eg, medial tibia) are not different in mild osteoarthritis versus non-osteoarthritis. Subregional thickness may be decreased in mild osteoarthritis. Semiquantitative scoring that assesses focal cartilage damage differentiates mild osteoarthritis from non-osteoarthritis.

Project description:BackgroundOsteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation.Materials and methodsThe type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.ResultsIn both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011).ConclusionSerum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.Level of evidenceLevel III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.

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Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

Publications

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

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