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Objective: To explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures. Materials and Methods: Knees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen's D was used as measure of effect size. Results: Maximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen's D 0.58–0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen's D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen's D 0.46–0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices. Conclusions: 3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus. [ABSTRACT FROM AUTHOR]

Objective: To explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures. Materials and Methods: Knees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen's D was used as measure of effect size. Results: Maximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen's D 0.58–0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen's D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen's D 0.46–0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices. Conclusions: 3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether baseline MRI-defined structural abnormalities are associated with subsequent change in laminar femorotibial cartilage transverse relaxation time (T2) of participants without radiographic signs, symptoms or risk factors for knee osteoarthritis (OA).Method: We studied all right knees with longitudinal MRI data of the refined Osteoarthritis Initiative Healthy Reference cohort. Baseline osteophytes, effusion-synovitis, Hoffa-synovitis, bone marrow lesions, cartilage lesions, and meniscus morphology and - extrusion were scored semiquantitatively from MR images by an expert reader. Deep and superficial layer cartilage T2 was computed in the medial and lateral femorotibial compartment (MFTC/LFTC) at baseline and at 1- and 4-year follow-up from multi-echo spin-echo MR images. Statistical analyses were performed using UNIANOVA.Results: 82 participants (age 54.1 ± 7.2y, BMI 24.2 ± 3.0 kg/m²; 61% women, bilateral Kellgren-Lawrence 0) were studied. Number of baseline MRI pathologies was not significantly associated with longitudinal change in MFTC or LFTC cartilage T2 over 1 or 4 years. Feature-specific analyses suggested that presence of baseline MFTC osteophytes may be associated with prolongation in superficial MFTC cartilage T2 over one (0.8 vs. 0.0 ms, p = 0.02) and four years (2.3 vs. 0.9 ms, p = 0.01), and that MFTC meniscal damage or extrusion may be associated with prolongation in deep layer T2 times over the first year (0.7 vs. 2.1 ms, p = 0.02).Conclusions: Our study does not provide evidence that, in knees without radiographic OA, baseline structural MRI abnormalities are strongly related to compositional progression during normal aging and/or the potentially earliest phases of the disease as measured by cartilage T2. [ABSTRACT FROM AUTHOR]

Objectives: The infrapatellar fat pad (IPFP) represents intraarticular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of proinflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on the IPFP volume. Methods: Intensive Diet and Exercise for Arthritis (IDEA) was a single-blinded, single-center, 18-month, prospective, randomized controlled trial that enrolled 454 overweight and obese older adults with knee pain and radiographic osteoarthritis. Participants were randomized to 1 of 3 groups: exercise-only control (E), diet-induced weight loss (D), and diet-induced weight loss + exercise (D+E). In a subsample (n = 106; E: n = 36, D: n = 35, and D+E: n = 35), magnetic resonance images were acquired at baseline and at the 18-month follow-up, from which we analyzed IPFP volume, surface areas, and thickness in this secondary analysis. Results: The average weight loss amounted to 1.0% in the E group, 10.5% in the Dgroup, and 13.0% in the D+E group. A significant (p < 0.01) reduction in IPFP volume was observed in the E (2.1%), D (4.0%), and D+E (5.2%) groups. The IPFP volume loss in the D+E group was significantly greater than that in the E group (p < 0.05) when not adjusting for parallel comparisons. Across intervention groups, there were significant correlations between IPFP volume change, individual weight loss (r = 0.40), and change in total body fat mass (dual-energy X-ray absorptiometry; r = 0.44, n = 88) and in subcutaneous thigh fat area (computed tomography; r = 0.32, n = 82). Conclusions: As a potential link between obesity and knee osteoarthritis, the IPFP was sensitive to intervention by diet and/or exercise, and its reduction was correlated with changes in weight and body fat. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement.Methods: Knees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T0) and 2 years before T0 (T-2) were compared using conditional logistic regression.Results: One hundred and nineteen knees from 102 participants (55.5 % women; age 64.2 ± 8.7 [mean ± SD] years) were studied. Fixed-location JSW change at 22.5 % from medial to lateral differed more between replaced and control knees (case-control [cc] OR = 1.57; 95 % CI: 1.23-2.01) than minimum medial JSW change (ccOR = 1.38; 95 % CI: 1.11-1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement.Conclusions: Discrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement.Key Points: • Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW. • MRI predicts knee replacement with similar accuracy to radiographic JSW. • MRI reveals greater cartilage thinning and thickening prior to knee replacement. [ABSTRACT FROM AUTHOR]

Objective To determine whether an anabolic drug (sprifermin) is capable of reducing cartilage loss wherever it occurs in a given knee, using a subject-specific, location-independent analysis of cartilage change in patients with knee osteoarthritis (OA). Methods Study participants (n = 168; ages ≥40 years, 69% women) had symptomatic femorotibial OA not confined to the medial compartment. Sprifermin (10, 30, or 100 μg) or placebo was injected intraarticularly 3 times over 3 weeks, both after randomization (baseline) and 3 months later. Coronal magnetic resonance images were acquired at baseline and 3, 6, and 12 months after treatment. The femorotibial cartilage of each subject was segmented, and changes in cartilage thickness were computed across 16 subregions. Location-independent post hoc analysis was used to compute summary scores of negative and positive changes in the subregions, summarized as the total cartilage thinning sum score (ThCTnS) and the total cartilage thickening sum score (ThCTkS), capturing change in either direction in each knee. Ordered values of the magnitude of subject-specific subregional changes in thickness were determined. The ThCTnS and ThCTkS in each sprifermin dose group at 12 months of followup were compared with the values in the matched placebo groups, using the Wilcoxon-Mann-Whitney test. Results The mean ± SD ThCTnS was −591 ± 617 μm (median −360 μm, Q1/Q3 = −820/−200 μm) in patients treated with 100 μg sprifermin (n = 57), and −921 ± 777 μm (median −745 μm, Q1/Q3 = −1,190/−380 μm) in patients given placebo (n = 18). The mean difference in the ThCTnS between the 100-μg sprifermin group and the placebo group was 331 μm (95% confidence interval [95% CI] 24, 685), a difference that was statistically significant ( P = 0.03). The mean difference in the ThCTkS in the 100-μg sprifermin group compared with the placebo group was 237 μm (95% CI 34, 440), also a statistically significant difference ( P = 0.028). Conclusion Sprifermin not only increases cartilage thickness, but also reduces cartilage loss. Subject-specific, location-independent analysis of both cartilage thinning and thickening represents a sensitive and informative approach for studying the effects of disease-modifying OA drugs. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common joint disorder. The Osteoarthritis Initiative (OAI) is a multicentre, longitudinal, prospective observational cohort study of knee OA that aims to provide publicly accessible clinical datasets, images and biospecimens, to enable researchers to investigate factors that influence the onset and development of OA, and evaluate biomarkers that predict and track the course of the disease. In this Perspectives, we describe the rationale and design of the OAI and its cohort, discuss imaging protocols and summarize image analyses completed to date. We include descriptive analyses of publicly available longitudinal (2-year) data of changes in cartilage thickness in a core sample of 600 knees from 590 participants in the OAI progression subcohort. Furthermore, we describe published methodological and applied imaging research that has emerged from OAI pilot studies and OAI data releases, and how these studies might contribute to clinical development of biomarkers for assessing the efficacy of intervention trials. [ABSTRACT FROM AUTHOR]

Objective To investigate whether rates of cartilage loss differ in knees with frequent baseline pain versus those without pain, after adjustment for radiographic osteoarthritis (OA) stage. Methods One knee in each of 718 Osteoarthritis Initiative participants was examined: 310 with calculated Kellgren/Lawrence (K/L) grade 2, 299 with calculated K/L grade 3, and 109 with calculated K/L grade 4. Twelve-month change in (subregional) cartilage thickness was assessed by magnetic resonance imaging. Change in cartilage thickness in the central subregion of the weight-bearing medial femoral condyle and ordered value 1 (OV1) were selected as primary end points. Frequent knee symptoms were defined as pain, aching, or stiffness on most days of at least 1 month during the previous year. Results The mean 12-month rate of change in cartilage thickness in the central subregion of the medial femoral condyle was −12 μm (standardized response mean [SRM] −0.15) in knees without pain (n = 146), −27 μm (SRM −0.25) in those with infrequent pain (n = 255), and −54 μm (SRM −0.32) in those with frequent pain (n = 317). Rates differed significantly between frequently painful knees and pain-free knees after adjustment for age, sex, body mass index, and calculated K/L grade ( P = 0.011, R2 = 2.6%, partial R2 for frequent pain = 1.4%). Similar results were found in stratified samples of calculated K/L grade 2/calculated K/L grade 3 knees, and in analyses restricted to knees with consistent pain frequency between baseline and followup. OV1 results showed similar trends but were not significant. Conclusion Knees with frequent pain display greater rates of medial cartilage loss longitudinally than knees without pain, with or without adjustment or stratification for radiographic disease stage. Enrollment of participants with frequent knee pain in clinical trials can increase the observed rate of structural progression (i.e., cartilage loss) and sensitivity to change. [ABSTRACT FROM AUTHOR]

Quantitative measures of cartilagemorphology (i.e., thickness) represent potentially powerful surrogate endpoints in osteoarthritis (OA). These can be used to identify risk factors of structural disease progression and can facilitate the clinical efficacy testing of structure modifying drugs in OA. This paper focuses on quantitative imaging of articular cartilage morphology in the knee, and will specifically deal with different cartilage morphology outcome variables and regions of interest, the relative performance and relationship between cartilage morphology measures, reference values for MRI-based knee cartilage morphometry, imaging protocols for measurement of cartilage morphology (including those used in the Osteoarthritis Initiative), sensitivity to change observed in knee OA, spatial patterns of cartilage loss as derived by subregional analysis, comparison of MRI changes with radiographic changes, risk factors of MRI-based cartilage loss in knee OA, the correlation of MRI-based cartilage loss with clinical outcomes, treatment response in knee OA, and future directions of the field. [ABSTRACT FROM AUTHOR]

The article presents a study on the relationship between subchondral bone plate exposure and prevalence of knee pain in osteoarthritis (OA) patients. It is stated in the study that knee pain is OA's most common symptom, caused by the loss of articular cartilage and subchondral bone plate exposure. It notes that the study assessed the knee pain and used imaging techniques to analyze the denuded bone areas. It also mentions that the study found that pain was associated with percent denuded bone.

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. [ABSTRACT FROM AUTHOR]

Exercise remains an extremely popular leisure time activity in many countries throughout the western world. It is widely promoted in the lay press as having salutory benefits for weight control, disease management advantages for cardiovascular disease and diabetes, in addition to improving psychological well-being amongst an array of other benefits. In contrast, however, the lay press and community perception is also that exercise is potentially deleterious to one's joints. The purpose of this review is to consider what osteoarthritis (OA) is and provide an overview of the epidemiology of OA focusing on validated risk factors for its development. In particular the role of both exercise and occupational activity in OA will be described as well as the role of exercise to the joints’ tissues (particularly cartilage) and the role of exercise in disease management. Despite the common misconception that exercise is deleterious to one's joints, in the absence of joint injury there is no evidence to support this notion. Rather it would appear that exercise has positive salutory benefits for joint tissues in addition to its other health benefits. [ABSTRACT FROM AUTHOR]

Quantitative imaging of musculoskeletal tissue, including radiography, computed tomography (CT), and magnetic resonance imaging (MRI), has become the essential methodology in clinical practice for diagnosis and monitoring of various musculoskeletal conditions. Furthermore, quantitative imaging technologies have become indispensable for research and development in diseases of the human skeleton. Standardized methods of image analysis have been developed through the years to quantify measurements on bone and cartilage with high precision and accuracy. Key areas of musculoskeletal disease where quantitative imaging is currently employed are osteoporosis and arthritis. [ABSTRACT FROM AUTHOR]

The objective of this work was to develop a methodology for measuring cartilage thickness in anatomically based subregions in the tibial and in the central weight-bearing femoral cartilage from magnetic resonance (MR) images. The tibial plateau was divided into a central area of the total subchondral bone area (tAB), and anterior, posterior, internal, and external subregions surrounding it. In the weight-bearing femoral condyles, central, internal, and external subregions were determined. The Euclidean distance between the tAB and cartilage surface was used for determining cartilage thickness. The reproducibility of the method was evaluated on test-retest data sets of 12 participants (six healthy, six with osteoarthritis). The subregion size was varied systematically to study the influence on the reproducibility. The size of the subregions was highly consistent under conditions of repositioning (standard deviation 0.0%-0.3%). The precision errors for regional mean cartilage thickness measurements ranged from 19 µm (1.5%) to 84 µm (4.7%). The computation of regional cartilage thickness values from segmented MR images is shown to be highly reproducible and robust under conditions of joint repositioning. In longitudinal studies, this technique may substantially enhance the ability of quantitative MRI to monitor structural changes in osteoarthritis at narrow time intervals. [ABSTRACT FROM AUTHOR]

Newly developed fuzzy logic-derived structural parameters were used to characterize trabecular bone architecture in high-resolution magnetic resonance imaging (HR-MRI) of human cadaver calcaneus specimens. These parameters were compared to standard histomorphological structural measures and analyzed concerning performance in discriminating vertebral fracture status and estimating proximal femur fracture load. Sets of 60 sagittal 1.5 T and 3.0 T HR-MRI images of the calcaneus were obtained in 39 cadavers using a fast gradient recalled echo sequence. Structural parameters equivalent to bone histomorphometry and fuzzy logic-derived parameters were calculated using two chosen regions of interest. Calcaneal, spine, and hip bone mineral density (BMD) measurements were also obtained. Fracture status of the thoracic and lumbar spine was assessed on lateral radiographs. Finally, mechanical strength testing of the proximal femur was performed. Diagnostic performance in discriminating vertebral fracture status and estimating femoral fracture load was calculated using regression analyses, two-tailed t-tests of significance, and receiver operating characteristic (ROC) analyses. Significant correlations were obtained at both field strengths between all structural and fuzzy logic parameters ( r up to 0.92). Correlations between histomorphological or fuzzy logic parameters and calcaneal BMD were mostly significant ( r up to 0.78). ROC analyses demonstrated that standard structural parameters were able to differentiate persons with and without vertebral fractures (area under the curve [AZ] up to 0.73). However, none of the parameters obtained in the 1.5-T images and none of the fuzzy logic parameters discriminated persons with and without vertebral fractures. Significant correlations were found between fuzzy or structural parameters and femoral fracture load. Using multiple regression analysis, none of the structural or fuzzy parameters were found to add discriminative value to BMD alone. In summary significant correlations were obtained at both field strengths between all structural and fuzzy logic parameters. However, fuzzy logic-based calcaneal parameters were not well suited for vertebral fracture discrimination. Although significant correlations were found between fuzzy or structural parameters and femoral fracture load, multiple regression analysis showed limited improvement for estimating femoral failure load in addition to femoral BMD alone. Local femoral measurements are still needed to estimate femoral bone strength. Overall, parameters obtained at 3.0 T performed better than those at 1.5 T. [ABSTRACT FROM AUTHOR]

Vertebral fractures represent the hallmark of osteoporosis. Here, we test the hypotheses that (sub)cortical bone strength and density predict failure better than trabecular core strength and density, and that elderly women display lower failure stress of thoracic vertebrae than men. We examined the vertebral bodies T3 to L5 in 39 spines from elderly donors (23 women; 16 men; age 79 ± 11 years). Peripheral quantitative computed tomography was used to measure total, trabecular, and (sub)cortical bone density. Mechanical tests were performed in functional spinal units, planoparallel sections of vertebrae, trabecular cores, and (sub)cortical ring specimens. The failure stress decreased with descending vertebral level. Failure stress was highest for the (sub)cortical rings and planoparallel sections and lowest for the trabecular core. The failure stress did not differ significantly between men and women. Mechanical strength of the functional unit was more strongly correlated with the strength of the (sub)cortical ring (r = 0.78) than with that of the trabecular core (r = 0.62). However, total density was more highly correlated with mechanical strength of the same and remote vertebrae (r = 0.63) than trabecular (r = 0.50) or (sub)cortical density (r = 0.36), respectively. The results show that vertebral strength is similar in elderly women and men. Strength of (sub)cortical bone provides significantly better prediction of strength of functional spinal units than that of the trabecular core. However, total density predicts functional segment failure stress with higher accuracy than (sub)cortical or trabecular density and is thus recommended for predicting fracture strength clinically. [Copyright &y& Elsevier]

Quantifying differences in joint loading for coxa vara and coxa valga is important for understanding what constitutes a pathological deformity. Prior free-body analyses for varus and valgus femora suggest that the loading direction in single-leg stance becomes more vertical for coxa valga and more horizontal for coxa vara. The objectives of this study were: 1) to apply a density-based load estimation technique to varus and valgus femora; 2) to infer potential differences in femoral loading for varus and valgus femora from the density; and 3) to compare the results with previous studies of femoral loading for single-leg stance. Representative valgus, normal, and varus femora from male cadavers were scanned in the plane of the femoral neck using computed tomography. A two-dimensional finite element model, including the density data from the CT scans, was constructed for each femur. A density-based bone load estimation method was used to determine the dominant loading pattern, and an average load direction was calculated. The average load direction varied consistently from more vertical for coxa valga to more horizontal for coxa vara. The results indicate that the differences in loading directions reduce the risk of epiphyseal slip or neck fracture in coxa vara and increase the tendency for subluxation or dislocation in coxa valga. Agreement between relative load angles from the density-based load estimation and free-body analyses confirms that internal femoral density is adapted to applied loads regardless of external femoral geometry. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the use of an unloading brace can increase the thickness of cartilage regenerate after microfracture surgery. Methods: This is a randomized (1:1) controlled clinical trial. Twenty-four patients who underwent microfracture between 2012 and 2015 were identified and were randomly assigned to an unloading brace group or a no-brace group. All patients were kept non-weight bearing for the first eight weeks after surgery and then patients in the intervention group began using an unloading brace for an average of 63.9 (SD = 41.6) days to protect clot stability by exerting a varus or valgus force on the knee to decrease the force on the knee's lateral or medial compartment, respectively. Quality of the cartilage repair was assessed with knee magnetic resonance imaging to determine repair tissue thickness (primary outcome), repair tissue volume, and T2 relaxation times at 12 and 24 months after surgery. Clinical outcomes were evaluated with KOOS, Tegner, SF12, and Lysholm questionnaires at six, 12 and 24 months after surgery. Results: Three patients were lost to follow-up, resulting in 21 patients ultimately analyzed. The unloading brace repair tissue was greater than the no-brace group in volume (26.8 ± 23.7 mm3 vs − 8.4 ± 22.7 mm3, p = 0.005) and thickness (0.2 ± 0.2 mm versus − 0.4 ± 0.3 mm, p = 0.001) at 12 months and in cartilage thickness in the unloading brace group at 24 months (0.4 ± 0.4 mm versus − 0.1 ± 0.3 mm, p = 0.029). There was a positive correlation between wearing the brace longer and improved 6-month KOOS symptom scores (r = 0.82, p = 0.013), 6-month KOOS QOL scores (r = 0.80, p = 0.017), 6-month Tegner scores (r = 0.94, p = 0.002), and Tegner score changes from baseline to 6 months (r = 0.80, p = 0.032). Conclusion: This study found a significant mid-term increase in cartilage repair tissue thickness following unloading bracing in patients recovering from microfracture for isolated chondral defects. Level of evidence: II. [ABSTRACT FROM AUTHOR]

Objectives To describe associations between MRI markers with knee symptoms in young adults. Methods Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008–2010) and at the 6- to 9-year follow-up (CDAH-3; 2014–2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. Results The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s. d. 2.72) and 43.27 (s. d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P  < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P  = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P  = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P  = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P  = 0.001] and knee symptoms assessed after 6–9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P  < 0.001] and 6–9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P  = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6–9 years. Conclusion BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults. [ABSTRACT FROM AUTHOR]

Currently no disease-modifying osteoarthritis drug has been approved for the treatment of osteoarthritis (OA) that can reverse, hold, or slow the progression of structural damage of OA-affected joints. The reasons for failure are manifold and include the heterogeneity of structural disease of the OA joint at trial inclusion, and the sensitivity of biomarkers used to measure a potential treatment effect. This article discusses the role and potential of different imaging biomarkers in OA research. We review the current role of radiography, as well as advances in quantitative three-dimensional morphological cartilage assessment and semiquantitative whole-organ assessment of OA. Although magnetic resonance imaging has evolved as the leading imaging method in OA research, recent developments in computed tomography are also discussed briefly. Finally, we address the experience from the Foundation for the National Institutes of Health Biomarker Consortium biomarker qualification study and the future role of artificial intelligence. [ABSTRACT FROM AUTHOR]

Quantitative measures of cartilage morphology ("cartilage morphometry") extracted from high resolution 3D magnetic resonance imaging (MRI) sequences have been shown to be sensitive to osteoarthritis (OA)-related change and also to treatment interventions. Cartilage morphometry is therefore nowadays widely used as outcome measure for observational studies and randomized interventional clinical trials. The objective of this narrative review is to summarize the current status of cartilage morphometry in OA research, to provide insights into aspects relevant for the design of future studies and clinical trials, and to give an outlook on future developments. It covers the aspects related to the acquisition of MRIs suitable for cartilage morphometry, the analysis techniques needed for deriving quantitative measures from the MRIs, the quality assurance required for providing reliable cartilage measures, and the appropriate participant recruitment criteria for the enrichment of study cohorts with knees likely to show structural progression. Finally, it provides an overview over recent clinical trials that relied on cartilage morphometry as a structural outcome measure for evaluating the efficacy of disease-modifying OA drugs (DMOAD). [ABSTRACT FROM AUTHOR]

The article discusses advances in imaging technology which detailed theories about the pathophysiology of osteoarthritis (OA) in 2013. The advances are attributed to the use of semiquantitative and qualitative image analysis methodology and the availability of public databases. Theories on the relationship between obesity, leptin and OA, knee radiographic OA (ROA) and the application of magnetic resonance imaging (MRI) to the meniscus are enriched with the use of the technology.

2013 has witnessed the maturation of imaging science with rheumatology research, in part due to large, public databases. Using imaging in osteoarthritis (OA) as an example, breakthroughs include further elucidation of the relationship between obesity and OA, and identification of the importance of bone and meniscus shape in OA development. [ABSTRACT FROM AUTHOR]

Background: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.Methods: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.Results: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).Conclusions: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA.Trial Registration: Clinicaltrials.gov identification: NCT03883568. [ABSTRACT FROM AUTHOR]

Objective To investigate whether a clinically relevant change in knee function in patients with or at risk for osteoarthritis (OA) of the knee is associated with concurrent or prior change in thigh muscle strength. Methods Participants in the Osteoarthritis Initiative (n = 2,675 [1,485 women and 1,190 men]) with available measurements of isometric muscle strength at baseline, 2-year follow-up, and 4-year follow-up were grouped into those with greater than minimum clinically important worsening (score of ≥6 [of a possible 68] on the Western Ontario and McMaster Universities Osteoarthritis Index function subscale) between 2-year follow-up and 4-year follow-up, those with greater than minimum clinically important improvement, and those without relevant change. Changes in isometric muscle strength concurrent with function change (between 2-year follow-up and 4-year follow-up) and preceding function change (between baseline and 2-year follow-up), with 95% confidence intervals (95% CIs), were determined, and differences between groups were assessed by analysis of covariance. Results Concurrent loss in extensor muscle strength in participants with worsening knee function during the 2-year follow-up−4-year follow-up period differed significantly from that in participants without change in knee function (−4.6% [95% CI −6.8, −2.4] and −2.2% [95% CI −3.0, −1.4], respectively; P = 0.03), as did the concurrent increase in strength among those with functional improvement (2.2% [95% CI −0.3, 4.7]; P < 0.0001). This increase in strength among subjects with improved function remained significantly different from the change in subjects with no change in function after adjustment for covariates, but was preceded by a greater loss in strength (−7.7% [95% CI −10.3, −5.0], P = 0.02) during the baseline−year 2 period compared to those without change in function during the year 2−year 4 period (−4.3% [95% CI −5.2, −3.4]). The decrease in strength during the baseline−year 2 period in those with worsening knee function during the year 2−year 4 period (−4.5% [95% CI −6.9, −2.2]) did not differ significantly from that in patients without a change in function ( P = 0.87). No differences in changes in flexor muscle strength were observed between groups. Conclusion These findings suggest that there is a positive concurrent longitudinal association between change in extensor muscle strength and worsening/improvement in knee function in patients with knee OA. However, a corresponding change in thigh muscle strength preceding the change in function was not observed. [ABSTRACT FROM AUTHOR]

Thigh subcutaneous (SCF) and intermuscular (IMF) fat have been associated with joint health and function. Here, we explore the (sex-specific) responsiveness of SCF, IMF, and muscle during longitudinal weight loss and gain, as well as the change in questionnaire-based and physical performance-based knee function measures. This exploratory study included 103 Osteoarthritis Initiative (OAI) participants, who displayed a ≥10% weight loss or gain between baseline (BL) and 2-year (Y2) follow-up (and maintained half of that weight loss until year 4) and had axial 3T magnetic resonance images (MRI) for measuring SCF, IMF, and muscle cross sectional areas (CSAs). The standardized response mean (SRM = mean divided by the standard deviation of the change) was used as a measure of responsiveness. A total of 52 OAI participants (73% women) displayed ≥10% weight loss, and 51 (67% women) ≥10% weight gain. Both SCF and IMF CSAs showed a significant decrease (mean change) with weight loss (SCF: −22%, SRM = −1.2; IMF: −15%, SRM = −0.7) and a significant increase with weight gain (SCF: +27%, SRM = 1.1; IMF: +21%, SRM = 0.6). Muscle CSAs showed significant changes during weight loss (extensor: −8.3%, SRM = −1.1; flexor: −7.2%, SRM = −1.0), but not during weight gain. Knee function measures were not relevantly associated with bidirectional changes in body weight. SCF and IMF CSAs are highly responsive to bidirectional weight change, whereas muscle CSAs were only responsive to weight loss. These findings highlight that MRI represents a sensitive tool for monitoring changes in thigh adipose tissue composition that may be applied during specific diet and/or exercise interventions. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Objective: The aim of the study was to determine whether tibiofemoral contact stress predicts risk for worsening knee pain over 84 ms in adults aged 50–79 yrs with or at elevated risk for knee osteoarthritis. Design: Baseline tibiofemoral contact stress was estimated using discrete element analysis. Other baseline measures included weight, height, hip-knee-ankle alignment, Kellgren-Lawrence grade, and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Logistic regression models assessed the association between baseline contact stress and 84-mo worsening of Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Results: Data from the dominant knee (72.6% Kellgren-Lawrence grade 0/1 and 27.4% Kellgren-Lawrence grade ≥ 2) of 208 participants (64.4% female, mean ± SD body mass index = 29.6 ± 5.1 kg/m2) were analyzed. Baseline mean and peak contact stress were 3.3 ± 0.9 and 9.4 ± 4.3 MPa, respectively. Forty-seven knees met the criterion for worsening pain. The highest tertiles in comparison with the lowest tertiles of mean (odds ratio [95% confidence interval] = 2.47 [1.03–5.95], P = 0.04) and peak (2.49 [1.03–5.98], P = 0.04) contact stress were associated with worsening pain at 84 mos, after adjustment for age, sex, race, clinic site, and baseline pain. Post hoc sensitivity analyses including adjustment for body mass index and hip-knee-ankle alignment attenuated the effect. Conclusions: These findings suggest that elevated tibiofemoral contact stress can predict the development of worsening of knee pain. [ABSTRACT FROM AUTHOR]

Purpose: Segmentation of trabecular bone from magnetic resonance (MR) images is a challenging task due to spatial resolution limitations, signal-to-noise ratio constraints, and signal intensity inhomogeneities. This article examines an alternative approach to trabecular bone segmentation using partial membership segmentation termed fuzzy C-means clustering incorporating local second order features for bone enhancement (BE-FCM) at multiple scales. This approach is meant to allow for a soft segmentation that accounts for partial volume effects while suppressing the influence of noise. Methods: A soft segmentation method was developed and evaluated on three different sets of data; interscan reproducibility was evaluated on six test-retest in vivo MR scans of the proximal femur, correlation between MR and HR-pQCT measurements was evaluated on 49 in vivo scans from the distal tibia, and the potential for fracture discrimination was evaluated using MR scans of calcaneus specimens from 15 participants with and 15 participants without vertebral fracture. The algorithm was compared to fuzzy clustering using the intensity as the only feature (I-FCM) and a dual thresholding algorithm. The metric evaluated was bone volume over total volume (BV/TV) within user-defined regions of interest. Results: BE-FCM had a higher interscan reproducibility (rms CV: 2.0%) compared to I-FCM (5.6%) and thresholding (4.2%), and expressed higher correlation to HR-pQCT data (r=0.79, p<10-11) compared to I-FCM (r=0.74, p<10-8) and thresholding (r=0.70, p<10-6). BE-FCM was also the method that was best able to differentiate between a control and a vertebral fracture group at a 95% significance level. Conclusions: The results suggest that trabecular bone segmentation by BE-FCM can provide a precise BV/TV measurement that is sensitive to pathology. The segmentation method may become useful in MR imaging-based quantification of bone microarchitecture. [ABSTRACT FROM AUTHOR]

Abstract: Systematic study of bones'' responses to loading requires simple non-invasive models in appropriate experimental animals where the applied load is controllable and the changes in bone quantifiable. Herein, we validate a model for applying axial loads, non-invasively to murine tibiae. This allows the effects of mechanical loading in both cancellous and cortical bone to be determined within a single bone in which genetic, neuronal and functional influences can also be readily manipulated. Using female C57Bl/J6 mice, peak strains at the tibial mid-shaft were measured during walking (<300 με tension) and jumping (<600 με compression) with single longitudinally oriented strain gauges attached to the bone''s lateral and medial surfaces. Identically positioned gauges were also used to determine, for calibration, the strains engendered by external applied compressive tibial loading between the flexed knee and ankle ex vivo. Applied loads between 5 and 13 N produced strains of 1150–2000 με on the lateral surface, and in vivo repetitions of these loads on alternate days for 2 weeks produced significant load magnitude-related increases in cortical bone formation that were similar in mice at 8, 12 and 20 weeks of age. Micro-CT scans showed that loading significantly increases trabecular bone volume in 8 week old mice, but modifies trabecular organization with decreases in trabecular bone volume in 12 and 20 week old mice. This model for loading the tibia has several advantages over other approaches, including scope to study the effects of loading in cancellous as well as cortical bone, against a background of either disuse or of treatment with osteotropic agents within a single bone in normal, mutant and transgenic mice. [Copyright &y& Elsevier]

It has been well established that articular cartilage is compositionally and mechanically inhomogeneous through its depth. To what extent this structural inhomogeneity is a prerequisite for appropriate cartilage function and integrity is not well understood. The first hypothesis to be tested in this study was that the depth-dependent inhomogeneity of the cartilage acts to maximize the interstitial fluid load support at the articular surface, to provide efficient frictional and wear properties. The second hypothesis was that the inhomogeneity produces a more homogeneous state of elastic stress in the matrix than would be achieved with uniform properties. We have, for the first time, simultaneously determined depth-dependent tensile and compressive properties of human patellofemoral cartilage from unconfined compression stress relaxation tests. The results show that the tensile modulus increases significantly from 4.1 ± 1.9 MPa in the deep zone to 8.3 ±3.7 MPa at the superficial zone, while the compressive modulus decreases from 0.73 ±0.26 MPa to 0.28 ± 0.16 MPa. The experimental measurements were then implemented with the finite-element method to compute the response of an inhomogeneous and homogeneous cartilage layer to loading. The finite-element models demonstrate that structural inhomogeneity acts to increase the interstitial fluid load support at the articular surface. However, the state of stress, strain, or strain energy density in the solid matrix remained inhomogeneous through the depth of the articular layer, whether or not inhomogeneous material properties were employed. We suggest that increased fluid load support at the articular surface enhances the frictional and wear properties of articular cartilage, but that the tissue is not functionally adapted to produce homogeneous stress, strain, or strain energy density distributions. Interstitial fluid pressurization, but not a homogeneous elastic stress distribution, appears thus to be a prerequisite for the functional and morphological integrity of the cartilage. [ABSTRACT FROM AUTHOR]

Objective To describe associations of body composition, physical activity and physical performance with knee cartilage thickness and subchondral bone area in young adults. Methods Body composition, physical activity and physical performance were measured 4–5 years prior to knee MRI. Cartilage thickness and bone area were measured quantitatively from MRI. Associations were assessed using linear regression analysis, with mediators being identified using mediation analysis. Results Participants (n = 186) were 31–41 years of age when the MRI was acquired and 48% were female. Greater lean mass was positively associated with cartilage thickness [β = 6.52 μm/kg (95% CI 0.86, 12.18)] and bone area [β = 13.37 mm2/kg (95% CI 5.43, 21.31)]. Physical performance measures were positively associated with cartilage thickness [long jump: β = 2.44 μm/cm (95% CI 0.70, 4.18); hand grip strength: 7.74 μm/kg (95% CI 1.50, 13.98); physical work capacity: 1.07 μm/W (95% CI 0.29, 1.85)] and bone area [long jump: β = 3.99 mm2/cm (95% CI 0.64, 7.34); hand grip strength: 19.06 mm2/kg (95% CI 7.21, 30.92); leg strength: 3.18 mm2/kg (95% CI 1.09, 5.28); physical work capacity: 3.15 mm2/W (95% CI 1.70, 4.60)]. Mediation analysis suggested these associations were mediated by lean mass (effect mediated: 27–95%). Conclusion Greater lean mass and better physical performance measured 4–5 years prior were associated with greater knee cartilage thickness and subchondral bone area in young adults, and the associations of physical performance were largely mediated by lean mass. These findings suggest lean mass may play an important role in maintaining knee joint health in young adults. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Objective: The aim of the study was to investigate whether muscle strength declines before or concurrent with incident knee pain in subjects with and without radiographic knee osteoarthritis. Design: Osteoarthritis initiative participants with incident knee pain (occurrence of infrequent/frequent knee pain during the past 12 mos at two consecutive follow-up time points (either years Y3 + Y4 or Y4 + Y5) were compared with controls (no incident knee pain) with 2-yr changes in knee extensor strength during BL➔Y2 (before) and Y2➔Y4 (concurrent). Results: Two hundred two knees (49% women, 40% radiographic knee osteoarthritis) displayed incident pain, and 439 did not (46% women, 23% radiographic knee osteoarthritis). Women with radiographic knee osteoarthritis displayed a significantly greater (P = 0.04) reduction in knee extensor strength concurrent with incident pain compared with controls (mean = −17.6 N vs. +4.5 N), but men did not. A similar trend was observed in women without radiographic knee osteoarthritis, but this was not statistically significant (P = 0.08). There was no significant relationship with change in extensor strength before incident pain (P ≥ 0.43). Conclusions: These results suggest that in women, incident knee pain is accompanied by a concurrent reduction in knee extensor strength, whereas loss in strength does not precede incident knee pain. The findings encourage interventional studies that attempt to attenuate a decline in extensor strength once knee symptoms occur. [ABSTRACT FROM AUTHOR]

Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug.Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.Design, Setting, and Participants: FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported.Interventions: Participants were randomized to 1 of 5 groups: intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks.Main Outcomes and Measures: The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%).Results: Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 μg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).Conclusions and Relevance: Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain.Trial Registration: ClinicalTrials.gov Identifier: NCT01919164. [ABSTRACT FROM AUTHOR]

Background and purpose — Knee extensor (KE) muscle weakness is a modifiable feature commonly observed in individuals with knee osteoarthritis (KOA) and constitutes a potential target for patient-specific interventions. Therefore, in this study, we explored whether KE weakness is associated with radiographic (medial and/or lateral) KOA progression and how this relationship differs depending on frontal plane knee alignment and sex. Patients and methods — We studied 3,075 knees (1,961 participants, 58% female) from the Osteoarthritis Initiative with radiographic Kellgren-Lawrence grade 1-3. Peak KE torque (Nm/kg) was assessed at baseline, and progression defined as fixed-location joint space width loss (≥ 0.7mm) in medial and lateral tibiofemoral compartments from baseline to 4-year follow-up. Knee-based generalized estimating equations, stratified by alignment (malaligned vs. neutral), estimated the relative risk (RR) of progression for those in the lowest (and middle) vs. highest KE torque group (split by tertiles). Secondary analyses explored whether this relationship was compartmental- or sex-specific. Results — Being in the lowest (or middle) compared with the highest torque group increased the risk of progression in neutrally aligned knees (relative risk [RR] 1.2 [95% CI 1.0-1.4]; and 1.2 [CI 1.0-1.4], respectively), but not after adjusting for age, sex, BMI, pain, and radiographic severity. In secondary analyses, women with neutral alignment in the lowest compared with the highest torque group had significantly increased risk of lateral compartment progression independent of age, BMI, disease severity, and pain (RR 1.3 [CI 1.0-1.8]). No association was observed between KE torque and KOA progression in men, irrespective of alignment. Interpretation — These results identify a potentially important clinical phenotype: KE weakness may be a more important risk factor for radiographic KOA progression in women without knee malalignment. [ABSTRACT FROM AUTHOR]

Objective: To determine whether 3D meniscal measures had similar sensitivity to longitudinal change as cartilage thickness; to what extent these measures are associated with longitudinal joint space width (JSW) change; and whether the latter associations differ between minimum (mJSW) and fixed-location JSW.Methods: Two-year changes in medial meniscal position and morphology, cartilage thickness (MRI) and minimum and fixed-location JSW (radiography) were determined in 35 Osteoarthritis Initiative knees [12 men, age: 67 (51-77) years; 23 women, age: 65 (54-78) years], progressing from baseline Kellgren-Lawrence grade ≤2 to knee replacement within 3-5 years. Multiple linear regression assessed the features contributing to JSW change.Results: Meniscal measures, cartilage thickness and JSW displayed similar sensitivity to change (standardised response mean≤|0.76|). Meniscal changes were strongly associated with JSW change (r≤|0.66|), adding ≤20% to its variance in addition to cartilage thickness change. Fixed-location JSW change (multiple r2=72%) was more strongly related to cartilage and meniscal change than mJSW (61%). Meniscal morphology explained more of fixed-location JSW and meniscal position more of mJSW.Conclusion: Meniscal measures provide independent information in explaining the variance of radiographic JSW change. Fixed-location JSW appears to be more reflective of structural change than mJSW and, hence, a potentially superior measure of structural progression.Key Points: • 3D positional/morphological meniscal measures change in rapidly progressing knees. • Similar sensitivity to 2-year change of quantitative meniscal/cartilage measures in rapid progression. • Changes in meniscal measures are strongly associated with radiographic JSW change. • Meniscal change provides information to explain JSW variance independent of cartilage. • Fixed-location JSW reflects structural disease stage more closely than minimum JSW. [ABSTRACT FROM AUTHOR]

Objective: To determine whether loss in thigh muscle strength prior to knee replacement is caused by reductions of muscle strength in the anatomic cross‐sectional area or by reductions of specific strength. Methods: All 100 of the participants in the Osteoarthritis Initiative who underwent knee replacement and whose medical records included data on thigh isometric muscle strength and magnetic resonance imaging (MRI) (58 women, and 42 men, mean ± SD age 65 ± 8 years, mean ± SD body mass index [BMI] 29 ± 5 kg/m2) were matched with a control (no knee replacement) for age, sex, height, BMI, and radiographic severity. Thigh muscle anatomic cross‐sectional area was determined by MRI at the research visit before knee replacement (time 0) and 2 years before time 0 (time −2). Specific strength (strength/anatomic cross‐sectional area) was calculated, and the measures were compared by conditional logistic regression (i.e., odds ratio [OR] per standard deviation). ORs adjusted for pain (ORadj) and 95% confidence intervals (95% CIs) were also calculated. Results: Knee replacement cases had significantly smaller extensor (but not flexor) anatomic cross‐sectional areas than controls at time 0 (women, ORadj 1.89 [95% CI 1.05–3.90]; men, ORadj 2.22 [95% CI 1.04–4.76]), whereas no significant differences were found at time −2. Women who had knee replacement showed lower levels of extensor specific strength than controls at time 0 (OR 1.59 [95% CI 1.02–2.50]), although this difference was not observed in men and did not maintain significance after adjustment for pain (ORadj 1.22 [95% CI 0.71–2.08]). Female cases lost significantly more extensor specific strength between time −2 and time 0 than controls (ORadj 3.76 [95% CI 1.04–13.60]), whereas no significant differences were noted at time −2, or in men. Conclusion: Prior to knee replacement, a significant reduction in knee extensor strength appears to occur in women through 2 mechanisms: one driven by pain (loss of specific strength) and one independent of pain (loss of muscle anatomic cross‐sectional area). Men who underwent knee replacement showed significantly reduced levels of extensor anatomic cross‐sectional area, but not significantly lower strength or specific strength. [ABSTRACT FROM AUTHOR]

Obesity is a potent risk factor for knee osteoarthritis (OA) that is driven by mechanical and potentially endocrine mechanisms, and it affects women more frequently than men. The infrapatellar fat pat (IPFP) represents a potential link between obesity, intra-articular inflammation and structural pathology. Here we investigate whether the IPFP is responsive to body weight loss/gain in women and how its responsiveness to weight change compares to that of subcutaneous fat (SCF) of the thigh. All female participants of the Osteoarthritis Initiative (OAI) with ≥10% weight loss/gain between baseline and a 2-year follow-up were included. Within-subject changes in IPFP volume and SCF cross-sectional areas (CSA) were determined from 3-T magnetic resonance imaging. Linear regression was used to assess the association between change in weight, IPFP volume, and SCF CSA. In the 38 participants with ≥10% weight loss over 2 years (age 59.3 ± 9.1 years, mean loss = 15.9%), there was a significant reduction in IPFP volume (-2.2%, p = 0.02) as well as in SCF CSA (-22%, p < 0.001). In the 34 participants with ≥10% gain (age 61.5 ± 8.7 years, mean gain = 15.9%), there was a significant increase in SCF CSA (+26%, p < 0.001) but not in IPFP volume (0.2%, p = 0.87). Weight change was significantly associated with SCF CSA change (r = 0.76, p < 0.001) but not with IPFP volume change (r = 0.11, p = 0.37). In this first longitudinal, observational study investigating the responsiveness of IPFP and SCF to weight change, IPFP morphology was found responsive to weight loss but not to weight gain. Overall, the responsiveness of the IPFP was substantially less than that of the SCF. [ABSTRACT FROM AUTHOR]

Objective: Patellofemoral cartilage changes have been evaluated in knee trauma and osteoarthritis; however, little is known about changes in patellar and trochlear cartilage thickness, T2 relaxation-time and subchondral bone plate area (tAB) during growth. Our prospective study aimed to explore longitudinal change in patellofemoral cartilage thickness, T2 and tAB in adolescent athletes, and to compare these data with those of mature (i.e., adult) athletes.Materials and Methods: 20 adolescent (age 16±1years) and 20 mature (46±5years) volleyball players were studied over 2-years (10 men and 10 women each group). 1.5T MRI 3D-VIBE and multi-echo spin-echo sequences were acquired at baseline and 2-year follow-up. Using manual segmentation and 3D reconstruction, longitudinal changes in patellar and trochlear cartilage thickness, patellar cartilage T2 (mono-exponential decay curve with five echoes [9.7-67.9ms]), and patellar and trochlear tAB were determined.Results: The annual increase in both patellar and trochlear cartilage thickness was 0.8% (95% confidence interval [CI] 0.6, 1.0) and 0.6% (0.3, 0.9), for adolescent males and females respectively; the longitudinal gain in patellar and trochlear tAB was 1.3% (1.1, 1.5) and 0.5% (0.2, 0.8), and 1.6% (1.1, 2.2) and 0.8% (0.3, 0.7) for adolescent males and females, respectively (no significant between-sex differences). Mature athletes showed smaller gains in tAB, and loss of <1% of cartilage thickness annually. While no significant sex-differences existed in adolescent patellar T2 changes, mature males gained significantly greater T2 than mature females (p=0.002-0.013).Conclusions: Patellar and trochlear cartilage thickness and tAB were observed to increase in young athletes in late adolescence, without significant differences between sexes. Mature athletes displayed patellar cartilage loss (and T2 increases in mature males), potentially reflecting degenerative changes. [ABSTRACT FROM AUTHOR]

Artificial materials reflecting the mechanical properties of human bone are essential for valid and reliable implant testing and design. They also are of great benefit for realistic simulation of surgical procedures. The objective of this study was therefore to characterize two groups of self-developed synthetic foam structures by static compressive testing and by microcomputed tomography. Two mineral fillers and varying amounts of a blowing agent were used to create different expansion behavior of the synthetic open-cell foams. The resulting compressive and morphometric properties thus differed within and also slightly between both groups. Apart from the structural anisotropy, the compressive and morphometric properties of the synthetic foam materials were shown to mirror the respective characteristics of human vertebral trabecular bone in good approximation. In conclusion, the artificial materials created can be used to manufacture valid synthetic bones for surgical training. Further, they provide novel possibilities for studying the relationship between trabecular bone microstructure and biomechanical properties. [ABSTRACT FROM AUTHOR]

Objective: To explore to what extent three-dimensional measures of the meniscus and femorotibial cartilage explain the variation in medial and lateral femorotibial radiographic joint space width (JSW), in healthy men and women.Methods: The right knees of 87 Osteoarthritis Initiative healthy reference participants (no symptoms, radiographic signs or risk factors of osteoarthritis; 37 men, 50 women; age 55.0±7.6; BMI 24.4±3.1) were assessed. Quantitative measures of subregional femorotibial cartilage thickness and meniscal position and morphology were computed from segmented magnetic resonance images. Minimal and medial/lateral fixed-location JSW were determined from fixed-flexion radiographs. Correlation and regression analyses were used to explore the contribution of demographic, cartilage and meniscal parameters to JSW in healthy subjects.Results: The correlation with (medial) minimal JSW was somewhat stronger for cartilage thickness (0.54≤r≤0.67) than for meniscal (-0.31≤r≤0.50) or demographic measures (-0.15≤r≤0.48), in particular in men. In women, in contrast, the strength of the correlations of cartilage thickness and meniscal measures with minimal JSW were in the same range. Fixed-location JSW measures showed stronger correlations with cartilage thickness (r≥0.68 medially; r≥0.59 laterally) than with meniscal measures (r≤|0.32| medially; r≤|0.32| laterally). Stepwise regression models revealed that meniscal measures added significant independent information to the total variance explained in minimal JSW (adjusted multiple r2=58%) but not in medial or lateral fixed-location JSW (r2=60/51%, respectively).Conclusions: In healthy subjects, minimal JSW was observed to reflect a combination of cartilage and meniscal measures, particularly in women. Fixed-location JSW, in contrast, was found to be dominated by variance in cartilage thickness in both men and women, with somewhat higher correlations between cartilage and JSW in the medial than lateral femorotibial compartment. The significant contribution of the meniscus' position on minimal JSW reinforces concerns over validity of JSW as an indirect measure of hyaline cartilage. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether partial meniscectomy is associated with increased risk of radiographic osteoarthritis (ROA) and worsening cartilage damage in the following year.Methods: We studied 355 knees from the Osteoarthritis Initiative that developed ROA (Kellgren-Lawrence grade ≥ 2), which were matched with control knees. The MR images were assessed using the semi-quantitative MOAKS system. Conditional logistic regression was applied to estimate risk of incident ROA. Logistic regression was used to assess the risk of worsening cartilage damage in knees with partial meniscectomy that developed ROA.Results: In the group with incident ROA, 4.4 % underwent partial meniscectomy during the year prior to the case-defining visit, compared with none of the knees that did not develop ROA. All (n = 31) knees that had partial meniscectomy and 58.9 % (n = 165) of the knees with prevalent meniscal damage developed ROA (OR = 2.51, 95 % CI [1.73, 3.64]). In knees that developed ROA, partial meniscectomy was associated with an increased risk of worsening cartilage damage (OR = 4.51, 95 % CI [1.53, 13.33]).Conclusions: The probability of having had partial meniscectomy was higher in knees that developed ROA. When looking only at knees that developed ROA, partial meniscectomy was associated with greater risk of worsening cartilage damage.Key Points: • Partial meniscectomy is a controversial treatment option for degenerative meniscal tears. • Partial meniscectomy is strongly associated with incident osteoarthritis within 1 year. • Partial meniscectomy is associated with increased risk of worsening cartilage damage. [ABSTRACT FROM AUTHOR]

Thigh muscle weakness is a risk factor for incident radiographic and symptomatic knee osteoarthritis (KOA). The role of thigh muscle weakness in radiographic and/or symptomatic KOA progression remains elusive. Five hundred twenty-seven knees of 527 Osteoarthritis Initiative participants with baseline Kellgren-Lawrence grades 1 to 3 were included in this nested case-control study evaluating whether baseline muscle strength predicted symptomatic and/or radiographic KOA progression. Case knees (n = 1 73) displayed both medial tibiofemoral joint space loss (≥0.7 mm) and a persistent increase in Western Ontario McMasters Osteoarthritis Index pain (≥9 on a 0- to 100-point scale) over 24 to 48 months from baseline. Control knees (n = 354) included 174 with neither radiographic nor symptomatic progression, 91 with radiographic progression only, and 89 with symptomatic progression only. Isometric knee extensor and flexor strength were recorded at baseline. Using logistic regression models, muscle strength was not associated with case status. However, knee extensor (odds ratio, 1.7; 95% confidence interval, 1.1-3.3; P= 0.035) and flexor weakness (odds ratio, 2.0; 95% confidence interval, 1.1, 3.3; P = 0.016) predicted isolated symptomatic progression in males, but not in females. The results indicate that thigh muscle strength may affect symptomatic and structural progression differently in males with KOA and identify an important window for potentially lowering risk of symptomatic osteoarthritis progression in men. [ABSTRACT FROM AUTHOR]

Background: A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period.Methods: 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann-Whitney - Wilcoxon tests assessed differences between groups.Results: Fifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (-0.04, 0.08) vs. placebo 0.22, 95 % CI (-0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (-0.14, 95 % CI (-0.48, 0.19) vs. placebo 0.44, 95 % CI (-0.15, 1.04), p = 0.042) although no significant effects were seen from the baseline visit, or in Hoffa-synovitis, effusion-synovitis, menisci and osteophytes.Conclusions: In this post-hoc analysis cartilage showed less worsening from baseline to 12 months in the PFJ, and BMLs showed more improvement from 6 to 12 months for the whole knee.Trial Registration: ClinicalTrials.gov identifier: NCT01033994 . [ABSTRACT FROM AUTHOR]

Objective To determine whether thigh muscle strength predicts the risk of undergoing knee replacement surgery, independent of radiographic severity of osteoarthritis and pain. Methods Participants in the Osteoarthritis Initiative study who had received a knee replacement between the 12-month and 60-month follow-up visits (cases) were each matched with 1 control subject (who did not receive a knee replacement over 60 months) for age, sex, height, body mass index, baseline radiographic stage, and location of joint space narrowing. Isometric knee extensor and flexor strength was recorded biennially. The strength examination prior to knee replacement (≤2 years) was termed time 0, that 2 years prior to time 0 was termed time −2, and that 4 years prior to time 0 was termed time −4. Muscle strength in patients and controls was compared using paired t-tests and conditional logistic regression analysis adjusted for pain. Results. One hundred thirty-six participants (60% women, mean ± SD age 65 ± 9 years, body mass index 29 ± 4 kg/m2) received a knee replacement during follow-up, had strength data for at least time 0, and had a matched control. Knee extensor strength at time 0 (primary outcome measure) was significantly lower in female patients compared with controls ( P < 0.001, pain-adjusted odds ratio [ORadj] 1.72, 95% confidence interval 1.16-2.56), but no significant difference was observed in men. Results were similar for knee flexor strength at time 0 and for longitudinal change in extensor and flexor strength between time −2 and time 0. Thigh muscle strength at time −2 or time −4, or change between time −4 and time −2, did not predict the risk of undergoing knee replacement surgery in men or women. Conclusion Thigh muscle strength predicted the risk of undergoing knee replacement surgery in women, but not in men. The results of this study may identify a window during which the risk of undergoing knee replacement surgery in women can be modified. [ABSTRACT FROM AUTHOR]

Objective To evaluate the extent to which the current designs of clinical trials in knee osteoarthritis (OA) permit detection of a therapeutic effect of disease-modifying OA drugs (DMOADs) on the incidence of knee replacement, and to provide estimates of the required sample sizes. Methods We selected distinct subcohorts of the Osteoarthritis Initiative (OAI), based on available information on eligibility criteria for clinical knee OA trials () and additional subcohorts stratified for age, sex, and the severity of radiographic OA. The observed incidence of knee replacement in these OAI subcohorts was used to estimate the expected incidence of knee replacement in the control group of a clinical trial. Based on this estimate, the sample sizes required to detect hypothetical treatment effects on the incidence of knee replacement were calculated, assuming observation periods of 2, 5, or 7 years. Results The cumulative knee replacement incidence rates in the OAI subcohorts ranged from 0.9% to 12.9%. The corresponding sample sizes required to detect 50% improvement by the DMOAD, with a power of 80% and 95% confidence, were 5,459 and 362, respectively. Including only women with advanced age and radiographic OA increased the incidence of knee replacement and decreased the required sample size. Conclusion The sample sizes that are commonly used in clinical trials do not enable the effects of a DMOAD on incident knee replacement to be detected with sufficient power and confidence. The estimated incidence rates of knee replacement and the corresponding sample sizes are important for informing the design of trials for disease course-modifying effects as well as for socioeconomic evaluation of a DMOAD in terms of preventing knee replacement. [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 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 the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA). Methods. The study was a randomized, doubleblind, placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment-emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results. One hundred ninety-two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100-μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment-emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups. Conclusion. No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dosedependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns. [ABSTRACT FROM AUTHOR]

Background: Recent advances in hemophilia prophylaxis have raised the need for accurate noninvasive methods for assessment of early cartilage damage in maturing joints to guide initiation of prophylaxis. Such methods can either be semiquantitative or quantitative. Whereas semiquantitative scores are less time-consuming to be performed than quantitative methods, they are prone to subjective interpretation. Objective: To test the feasibility of a manual segmentation and a quantitative methodology for cross-sectional evaluation of articular cartilage status in growing ankles of children with blood-induced arthritis, as compared with a semiquantitative scoring system and clinical-radiographic constructs. Materials and methods: Twelve boys, 11 with hemophilia (A, n = 9; B, n = 2) and 1 with von Willebrand disease (median age: 13; range: 6-17), underwent physical examination and MRI at 1.5 T. Two radiologists semiquantitatively scored the MRIs for cartilage pathology (surface erosions, cartilage loss) with blinding to clinical information. An experienced operator applied a validated quantitative 3-D MRI method to determine the percentage area of denuded bone (dAB) and the cartilage thickness (ThCtAB) in the joints' MRIs. Quantitative and semiquantitative MRI methods and clinical-radiographic constructs (Hemophilia Joint Health Score [HJHS], Pettersson radiograph scores) were compared. Results: Moderate correlations were noted between erosions and dAB ( r = 0.62, P = 0.03) in the talus but not in the distal tibia ( P > 0.05). Whereas substantial to high correlations ( r range: 0.70-0.94, P < 0.05) were observed between erosions, cartilage loss, HJHS and Pettersson scores both at the distal tibia and talus levels, moderate/borderline substantial ( r range: 0.55-0.61, P < 0.05) correlations were noted between dAB/ThCtAB and clinical-radiographic constructs. Conclusion: Whereas the semiquantitative method of assessing cartilage status is closely associated with clinical-radiographic scores in cross-sectional studies of blood-induced arthropathy, quantitative measures provide independent information and are therefore less applicable for that research design. [ABSTRACT FROM AUTHOR]