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Objective To assess whether the presence of structural osteoarthritis (OA) features over as many as 4 years prior to incident radiographic OA increases the risk of radiographic OA in a nested, case-control design. Methods We studied 355 knees from the Osteoarthritis Initiative cohort that developed radiographic OA before the 48-month visit. They were matched one-to-one by sex, age, and contralateral knee radiographic status with a control knee. Magnetic resonance images (MRIs) were read for bone marrow lesions (BMLs), cartilage damage, meniscal damage (including tears and extrusion), Hoffa synovitis, and effusion synovitis. Conditional logistic regression was applied to assess the risk of radiographic OA with regard to the presence of BMLs (score ≥2), cartilage lesions (score ≥1.1), meniscal damage (any) and extrusion of ≥3 mm ± (score ≥2), and Hoffa and effusion synovitis (any). Time points were defined as incident radiographic OA visit (P0), 1 year prior to the detection of radiographic OA (P −1), 2 years prior to the detection of radiographic OA (P −2), etc. Results The presence of Hoffa synovitis (hazard ratio [HR] 1.76 [95% confidence interval (95% CI) 1.18-2.64]), effusion synovitis (HR 1.81 [95% CI 1.18-2.78]), and medial meniscal damage (HR 1.83 [95% CI 1.17-2.89]) at P −2 predicted radiographic OA incidence. At P −1, all features but meniscal extrusion predicted radiographic OA, with highest odds for medial BMLs (HR 6.50 [95% CI 2.27-18.62]) and effusion synovitis (HR 2.50 [95% CI 1.76-3.54]). The findings at P −3 and P −4 did not reach statistical significance. Conclusion Our findings indicate that the presence of specific structural features of MRI-detected joint damage 2 years prior to incident radiographic OA increases the risk of incident radiographic OA. However, 1 year prior to radiographic OA, the presence of almost any abnormal morphologic feature increases the risk of radiographic OA in the subsequent year. [ABSTRACT FROM AUTHOR]

Objective To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. Methods Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. Results Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA ( P < 0.01 for 24 months), 24-month change in tibial ( P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW ( P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated ( P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. Conclusion BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Knee pain and muscle weakness confer risk for knee osteoarthritis incidence and progression. The purpose of this study was to determine whether unilateral knee pain influences contralateral thigh muscle strength. Design: Of 4796 Osteoarthritis Initiative participants, 224 (mean T SD age, 63.9 T 8.9 yrs) cases could be matched to a control. Cases were defined as having unilateral knee pain (numerical rating scale, Q 4/10; Qinfrequent pain) and one pain-free knee (numerical rating scale, 0Y1; einfrequent pain; Western Ontario and McMaster Universities Arthritis Index, e 1). Controls were defined as having bilaterally pain-free knees (numerical rating scale, 0Y1; einfrequent pain; Western Ontario and McMaster Universities Arthritis Index, e 1). Maximal isometric muscle strength (N) was compared between limbs in participants with unilateral pain (cases) as well as between pain-free limbs of cases and controls. Results: Knee extensor/flexor strength in pain-free limbs of the cases was lower than that in bilaterally pain-free controls (j5.5%/j8.4%; P = 0.043/P = 0.022). Within the cases, maximum extensor/flexor strength was significantly lower in the painful limb than in the pain-free limb (j6.3%/4.1%; P G 0.0001/P = 0.015). Conclusions: These results suggest that strength in limbs without knee pain is associated with the pain status of the contralateral knee. The strength difference between unilateral pain-free cases and matched bilateral pain-free controls was similar to that between limbs in persons with unilateral knee pain. Lower strength caused by contralateral knee pain might be centrally mediated. [ABSTRACT FROM AUTHOR]

Objective: To investigate which magnetic resonance imaging (MRI)-based articular pathologies are predictive of subsequent medial femorotibial compartment quantitative cartilage thickness loss and therefore suitable for enrichment of clinical trials with participants showing a high likelihood for structural progression., Methods: Semiquantitative MRI Osteoarthritis Knee Score (MOAKS) assessments at baseline and quantitative cartilage thickness measurements at baseline and year-2 follow-up were performed in 599 participants (age 62 years; body mass index 31 kg/m 2 ; 59% female) from the Osteoarthritis Initiative-based Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium. Knees were classified as medial femorotibial compartment (MFTC) progressors or nonprogressors based on MFTC cartilage thickness change (smallest detectable change threshold -111 μm). Logistic regression was used to investigate the association between baseline presence and severity of MFTC MOAKS pathologies with subsequent MFTC progression. The standardized response mean (SRM) was computed to estimate the sensitivity to change that can be achieved when selecting knees based on MOAKS pathologies., Results: Presence of MFTC MOAKS cartilage damage (odds ratio [OR] 2.77 [95% confidence interval (95% CI) 1.76, 4.36]), MFTC bone marrow lesions (OR 2.69 [95% CI 1.89, 3.83]), medial meniscus extrusion or damage (OR 2.21 [95% CI 1.37, 3.55]), as well as MOAKS severity subscales for cartilage and meniscus damage were associated with subsequent progression. The SRM was greater in knees with than in knees without the presence of these pathologies and was associated with the severity of those pathologies., Conclusion: MRI-based grading of articular pathologies makes it possible to specifically select progressor knees suitable for inclusion in clinical trials but also to identify knees in which treatment is not indicated (e.g., knees without cartilage damage despite presence of radiographic osteoarthritis)., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To study whether layer-specific cartilage transverse relaxation time (T2) and/or longitudinal change is associated with clinically relevant knee osteoarthritis (OA) disease progression., Methods: The Foundation for the National Institutes of Health Biomarker Consortium was a nested case-control study on 600 knees from 600 Osteoarthritis Initiative participants. Progressor knees had both medial tibiofemoral radiographic joint space width (JSW) loss (≥0.7 mm) and a persistent increase in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (≥9 on a 0-100 scale) at 24-48 months from baseline (n = 194). Multiecho spin-echo (MESE) magnetic resonance images (MRIs) for cartilage T2 analysis had been acquired in the right knees only (97 progressor knees). These were compared to 104 control knees without JSW or pain progression. Fifty-three knees had JSW progression, and 57 pain progression only. Cartilage thickness segmentations obtained from double-echo steady-state MRI were matched to MESE MRI to extract superficial and deep femorotibial cartilage T2. Superficial medial femorotibial compartment (MFTC) T2 at baseline was the primary, and change in deep MFTC T2 between baseline and 12 months was the secondary analytic outcome of this post hoc exploratory study., Results: Baseline superficial MFTC T2 was significantly elevated in progressor knees (adjusted mean 47.2 msec [95% confidence interval (95% CI) 46.5, 48.0]) and JSW progression only knees (adjusted mean 47.3 msec [95% CI 46.3, 48.3]), respectively, versus non-progressor knees (45.8 msec [95% CI 45.0, 46.5]) after adjustment for age, sex, body mass index, WOMAC pain score, and medial joint space narrowing grade (analysis of covariance). Change in T2 was not significantly associated with case status., Conclusion: Baseline superficial, but not deep, medial cartilage T2 is associated with clinically relevant disease progression in knee OA., (© 2021 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression., Methods: The present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of <0.10 in univariate analysis were selected, including quantitative cartilage thickness and volume on magnetic resonance imaging (MRI), semiquantitative MRI markers, bone shape and area, quantitative meniscal volume, radiographic progression (trabecular bone texture [TBT]), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using 3 different stepwise selection methods (complex models versus parsimonious models)., Results: Among baseline biomarkers, the number of locations affected by osteophytes (semiquantitative), quantitative central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and semiquantitative Hoffa-synovitis predicted OA progression in most models (C statistic 0.641-0.671). In most models, 24-month changes in semiquantitative MRI markers (effusion-synovitis, meniscal morphologic changes, and cartilage damage), quantitative central medial femoral cartilage thickness, quantitative medial tibial cartilage volume, quantitative lateral patellofemoral bone area, horizontal TBT (intercept term), and urine N-telopeptide of type I collagen predicted OA progression (C statistic 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, which had a higher C statistic of 0.716-0.832., Conclusion: The present study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to experience progression of knee OA., (© 2021 American College of Rheumatology.)

Objective: To study the longitudinal performance of fully automated cartilage segmentation in knees with radiographic osteoarthritis (OA), we evaluated the sensitivity to change in progressor knees from the Foundation for the National Institutes of Health OA Biomarkers Consortium between the automated and previously reported manual expert segmentation, and we determined whether differences in progression rates between predefined cohorts can be detected by the fully automated approach., Methods: The OA Initiative Biomarker Consortium was a nested case-control study. Progressor knees had both medial tibiofemoral radiographic joint space width loss (≥0.7 mm) and a persistent increase in Western Ontario and McMaster Universities Osteoarthritis Index pain scores (≥9 on a 0-100 scale) after 2 years from baseline (n = 194), whereas non-progressor knees did not have either of both (n = 200). Deep-learning automated algorithms trained on radiographic OA knees or knees of a healthy reference cohort (HRC) were used to automatically segment medial femorotibial compartment (MFTC) and lateral femorotibial cartilage on baseline and 2-year follow-up magnetic resonance imaging. Findings were compared with previously published manual expert segmentation., Results: The mean ± SD MFTC cartilage loss in the progressor cohort was -181 ± 245 μm by manual segmentation (standardized response mean [SRM] -0.74), -144 ± 200 μm by the radiographic OA-based model (SRM -0.72), and -69 ± 231 μm by HRC-based model segmentation (SRM -0.30). Cohen's d for rates of progression between progressor versus the non-progressor cohort was -0.84 (P < 0.001) for manual, -0.68 (P < 0.001) for the automated radiographic OA model, and -0.14 (P = 0.18) for automated HRC model segmentation., Conclusion: A fully automated deep-learning segmentation approach not only displays similar sensitivity to change of longitudinal cartilage thickness loss in knee OA as did manual expert segmentation but also effectively differentiates longitudinal rates of loss of cartilage thickness between cohorts with different progression profiles., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: A high degree of meniscal body extrusion on knee magnetic resonance imaging has been shown to be strongly associated with development of knee osteoarthritis. However, very little is known about meniscal position in the asymptomatic knee and its natural history. Hence our objective was to study meniscal body position and its change over 4 years in asymptomatic adults., Methods: Cohort study using data from the Osteoarthritis Initiative (OAI) involving four clinical sites in the United States (Baltimore, Maryland, Pawtucket, Rhode Island, Columbus, Ohio, and Pittsburgh, Pennsylvania). We studied both knees from 118 subjects (mean age 55 years, 61% women, mean body mass index 24.4) from the OAI "non-exposed" reference cohort free of knee pain, radiographic knee osteoarthritis and risk factors for knee osteoarthritis at baseline. We assessed mid-coronal intermediate-weighted 3-Tesla magnetic resonance images from baseline and the 2- and 4-year follow-up visit. One observer measured tibia plateau, meniscal body width and meniscal body extrusion in both compartments. We calculated meniscal overlap distance on the tibial plateau, % coverage, and extrusion index compared to tibia width. Potential trends in position over the 4-year period were evaluated using a linear mixed-effects regression model., Results: The mean (SD) values at baseline for medial meniscal body extrusion and overlap distance were 1.64 mm (0.92) and 10.1 mm (3.5), and coverage was 34.4% (11.9). The corresponding values for the lateral compartment were 0.63 mm (0.73), 9.8 mm (2.4), and 31.0% (7.7). Medial meniscus body extrusion index was greater in female knees (p = 0.03). There was slight increase in medial meniscal body extrusion over 4 years (0.040 mm/year [95% CI: 0.019-0.062]). The other variables were relatively stable., Conclusions: In asymptomatic adults, the relative degree of meniscus body extrusion is more pronounced in female knees. Although a slight increase in extrusion over time was noted for the medial body, positions were relatively stable within subjects over time.