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Objective: 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., Methods: 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., Results: Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m 2 ), 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., Conclusions: 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. CLINICALTRIALS., Gov Identification: NCT00080171., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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 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., 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., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Cartilage spin-spin magnetic resonance imaging (MRI) relaxation time (T2) represents a promising imaging biomarker of "early" osteoarthritis (OA) known to be associated with cartilage composition (collagen integrity, orientation, and hydration). However, no longitudinal imaging studies have been conducted to examine cartilage maturation in healthy subjects thus far. Therefore, we explore T2 change in the deep and superficial cartilage layers at the end of adolescence., Methods: Twenty adolescent and 20 mature volleyball athletes were studied (each 10 men and 10 women). Multi-echo spin-echo (MESE) images were acquired at baseline and 2-year follow-up. After segmentation, cartilage T2 was calculated in the deep and superficial cartilage layers of the medial tibial (MT) and the central, weight-bearing part of the medial femoral condyle (cMF), using five echoes (TE 19.4-58.2 ms)., Results: 16 adolescent (6 men, 10 women, baseline age 15.8 ± 0.5 years) and 17 mature (nine men, eight women, age 46.5 ± 5.2 years) athletes had complete baseline and follow-up images of sufficient quality to compute T2. In adolescents, a longitudinal decrease in T2 was observed in the deep layers of MT (-2.0 ms; 95% confidence interval (CI): [-3.4, -0.6] ms; P < 0.01) and cMF (-1.3 ms; [-2.4, -0.3] ms; P < 0.05), without obvious differences between males and females. No significant change was observed in the superficial layers, or in the deep or superficial layers of the mature athletes., Conclusion: In this first pilot study on quantitative imaging of cartilage maturation in healthy, athletic subjects, we find evidence of cartilage compositional change in deep cartilage layers of the medial femorotibial compartment in adolescents, most likely related to organizational changes in the collagen matrix., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Substantial changes in articular cartilage composition and mechanical properties occur during the development of osteoarthritis (OA). While softening in the initial stage is reported and sometimes used as an indicator of early OA, there is a lack of data relating the macroscopic appearance of cartilage to its mechanical and histological properties in all stages of degeneration. Knowledge about the mechanical quality of the tissue is important for diagnostic reasons and the understanding of the development of OA., Design: The cartilage areas of 21 osteoarthritic human cadaver tibia plateaus were classified using the International Cartilage Repair Society (ICRS) system. A material testing device determined the Young's modulus of the cartilage by unconfined compression. Histological analysis used haematoxylin and eosin staining and Safranin-O staining for the evaluation of the Mankin score., Results: A correlation between increasing ICRS Grade and stiffness reduction was found (R2=0.69). Stiffness values were for ICRS Grades 1, 2 and 3: E1=0.50+/-0.14 MPa, E2=0.37+/-0.13 MPa and E3=0.28+/-0.12 MPa, respectively. The histological evaluation confirmed the ICRS classification (R2=0.74). A moderate correlation between Mankin score and cartilage stiffness was observed (R2=0.47)., Conclusions: The results indicate a relation between structural, mechanical and histological changes in all stages of the degeneration. With increasing ICRS Grade the cartilage stiffness, which is primarily influenced by the integrity of the extracellular matrix, decreases. Therefore, methods of stiffness determination such as indentation may be used to characterize cartilage in all stages of OA. However, the data suggest that differentiating between healthy cartilage and ICRS Grade 1 may be difficult using mechanical testing alone.