Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study.

OBJECTIVE: The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization. DESIGN: We included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization. RESULTS: 4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%). CONCLUSIONS: CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Clinical value of weight-bearing CT and radiographs for detecting patellofemoral cartilage visualized by MRI in the MOST study.

OBJECTIVE: The patellofemoral joint is frequently affected by osteoarthritis (PFOA) and is incompletely imaged on radiographs (XR). Weight-Bearing CT (WBCT) could offer advantages for visualization. This study determined the sensitivity, specificity, and accuracy of axial WBCT and lateral XR for detection of PFOA features in comparison with cartilage damage on MRI. DESIGN: A convenience sample of 60 right knees from the MOST cohort were analyzed. WBCT and XR were read for OARSI JSN score and MRI for MOAKS cartilage score by two experienced musculoskeletal radiologists blinded to participant. Using MOAKS scoring on MRI (referent standard), the sensitivity, specificity and accuracy of patellofemoral OARSI JSN scores based on WBCT and XR were compared. RESULTS: The mean ± SD age and BMI for the participants included (66.7% women) were 67.6 ± 9.8 years and 30.0 ± 5.3 kg/m2 respectively. WBCT demonstrated significantly greater sensitivity (0.85-0.97 on WBCT vs 0.47-0.57 on XR) and accuracy (0.85-0.92 on WBCT vs 0.48-0.57 on XR) for all parameters except lateral full-thickness cartilage loss (McNemar's test p-values all <0.001). There was moderate-to-strong and low-to-moderate agreement between PFOA findings on WBCT and XR, respectively, and semi-quantitative scores of PF cartilage on MRI. Inter-rater reliability for XR JSN [weighted kappa = 0.83 (0.64, 1.0)], WBCT JSN [kappa = 0.60 (0.48, 0.72)] and MRI MOAKS-CM [kappa = 0.70 (0.61, 0.79)] readings were good. CONCLUSION: WBCT demonstrates significantly greater sensitivity and accuracy than radiographs for identification of PFOA. Given the same Relative Radiation Level as XR and improved visualization, WBCT holds promise to improve understanding of the weight-bearing patellofemoral joint.

Reliability of a new scoring system for intraarticular mineralization of the knee: Boston University Calcium Knee Score (BUCKS).

BACKGROUND: The role of intra-articular mineralization in osteoarthritis (OA) is unclear. Its understanding may potentially advance our knowledge of knee OA pathogenesis. We describe and assess the reliability of a novel computed tomography (CT) scoring system, the Boston University Calcium Knee Score (BUCKS) for evaluating intra-articular mineralization. METHODS: We included subjects from the most recent study visit of the Multicenter Osteoarthritis Study (MOST) Study, a NIH-funded longitudinal cohort of community-dwelling older adults with or at risk of knee OA. All subjects underwent CT of bilateral knees. Each knee was scored at 28 scored locations (14 for cartilage, 6 for menisci, 6 for ligaments, 1 for joint capsule, and 1 popliteal-tibial vessels). A single musculoskeletal radiologist scored cartilage and meniscus subregions, as well as vascular calcifications assigning to each a score ranging from 0 to 3. The joint capsule, medial and lateral posterior meniscal roots, anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) and 2 collateral ligaments [medial collateral ligament (MCL)/lateral collateral ligament (LCL)] were each scored 0 or 1 for absence or presence of mineralization. To assess reliability, 31 subject CTs were reread 12 weeks later by the same reader and by a second reader and agreement was evaluated using a weighted kappa. RESULTS: The intra-reader reliability ranged from 0.92 for ligaments to 1.0 for joint capsule. The inter-reader reliability ranged from 0.94 for cartilage and ligaments, to 1.0 for joint capsule. CONCLUSION: BUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA.

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

PURPOSE: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. METHODS: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. RESULTS: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. CONCLUSIONS: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

The morphology of proximal tibiofibular joint (PTFJ) predicts incident radiographic osteoarthritis: data from Osteoarthritis Initiative.

OBJECTIVE: To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. METHODS: A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those with iROA. Control knees were matched one-to-one by sex, age and radiographic status with case knees. T2-weighted MR images were assessed at P0 (the visit when incident ROA was found on radiograph), P1 (1 year prior to P0) and at OAI baseline. The contacting area of PTFJ (S) and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. RESULTS: 354 case knees and 354 matched control knees were included, with a mean age of 60 and a mean body mass index (BMI) of 28 kg/m2. Baseline PTFJ morphological parameters (S, Sτ and Sυ) were significantly associated with iROA over 4 years, and these associations remained unchanged after adjustment for BMI, number of knee bending activities, self-reported knee injury and surgery. S, Sτ and Sυ were also significantly associated with iROA at P1 and P0. In subgroup analysed, S, Sτ and Sυ were associated with risks of incident joint space narrowing in the medial, but not the lateral tibiofemoral compartment. CONCLUSION: Greater contacting area, load-bearing area and posterior stress-bolstering area of PTFJ were associated with increased risks of iROA, largely in the medial tibiofemoral compartment.

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

OBJECTIVE: The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN: 141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS: Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS: This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

Quantitative measurement of cartilage volume is possible using two-dimensional magnetic resonance imaging data sets.

PURPOSE: 3D Magnetic resonance imaging (MRI) scans are generally used for quantitative cartilage measurements in knee osteoarthritis. However, a great deal of MRI data is from 2D scans, often thought to be unsuitable for quantitative cartilage assessment. The goal of our study was to demonstrate that mLACS, a modified version of the Local Area Cartilage Segmentation (LACS) method, could be used to measure cartilage volume on 2D MRI images. METHODS: We studied 301 randomly selected subjects from the OA Biomarkers Consortium FNIH Study, a nested case-control study within the Osteoarthritis Initiative (OAI). The study comprised four subgroups based on radiographic and pain progression. We compared mLACS applied to 2D TSE scans to LACS on 3D DESS data. The Pearson's correlation coefficient was used to establish agreement between LACS and mLACS, standardized response means (SRMs) for responsiveness, and intra-class correlation coefficients (ICCs) to measure reader precision. Logistic regression in a case/control analysis was used to compare the clinical validity between the two methods. RESULTS: We found R2 = 0.76 for the correlation between LACS and mLACs. For LACS, the responsiveness was SRM = 0.49 compared to 0.39 for mLACS. The odds ratios (OR) for the primary case/control analyses were 1.62 for LACS and 1.78 for mLACS. The intra and inter reader reproducibility values for mLACS were ICC = 0.90 and 0.86, respectively. CONCLUSION: This study has demonstrated that a reproducible, responsive, and clinically valid quantitative measurement of cartilage volume can be made using 2D TSE scans with a modest loss of responsiveness compared to 3D scans.

Is the atrophic phenotype of tibiofemoral osteoarthritis associated with faster progression of disease? The MOST study.

OBJECTIVE: To assess the associations of atrophic tibiofemoral osteoarthritis (OA) with progression of radiographic joint space narrowing (JSN) and magnetic resonance imaging (MRI)-defined progression of cartilage damage. DESIGN: Participants of the Multicenter Osteoarthritis (MOST) Study with available radiographic and MRI assessments at baseline and 30 months were included. The atrophic OA phenotype was defined as Osteoarthritis Research Society International (OARSI) grades 1 or 2 for JSN and grade 0 for osteophytes. Based on MRI, atrophic OA was defined as tibiofemoral (TF) cartilage damage grades ≥3 in at least 2 of 10 subregions with absent or tiny osteophytes in all TF subregions. Progression of JSN and cartilage loss on MRI, was defined as (1) no, (2) slow, and (3) fast progression. Co-variance and logistic regression with generalized estimated equations were performed to assess the association of atrophic knee OA with any progression, compared to non-atrophic OA knees. RESULTS: A total of 476 knees from 432 participants were included. There were 50 (10.5%) knees with atrophic OA using the radiographic definition, and 16 (3.4%) knees with atrophic OA using MRI definition. Non-atrophic OA knees more commonly exhibited fast progression of JSN and cartilage damage. Logistic regression showed that the atrophic phenotype of knee OA was associated with a decreased likelihood of progression of JSN and cartilage loss. CONCLUSION: In this sample, the atrophic phenotype of knee OA was associated with a decreased likelihood of progression of JSN and cartilage loss compared to the non-atrophic knee OA phenotype.

Quantitative measurement of medial femoral knee cartilage volume - analysis of the OA Biomarkers Consortium FNIH Study cohort.

OBJECTIVE: Large studies of knee osteoarthritis (KOA) require well-characterized efficient methods to assess progression. We previously developed the local-area cartilage segmentation (LACS) software method, to measure cartilage volume on magnetic resonance imaging (MRI) scans. The present study further validates this method in a larger patient cohort and assesses predictive validity in a case-control study. METHOD: The OA Biomarkers Consortium FNIH Project, a case-control study of KOA progression nested within the Osteoarthritis Initiative (OAI), includes 600 subjects in four subgroups based on radiographic and pain progression. Our software tool measured change in medial femoral cartilage volume in a central weight-bearing region. Different sized regions of cartilage were assessed to explore their sensitivity to change. The readings were performed on MRI scans at the baseline and 24-month visits. We used standardized response means (SRMs) for responsiveness and logistic regression for predictive validity. RESULTS: Cartilage volume change was associated strongly with radiographic progression (odds ratios (OR) = 4.66; 95% confidence intervals (CI) = 2.85-7.62). OR were significant but of lesser magnitude for the combined radiographic and pain progression outcome (OR = 1.70; 95% CI = 1.40-2.07). For the full 600 subjects, theSRM was -0.51 for the largest segmented area. Smaller areas of cartilage segmentation were also able to predict the case-control status. The average reader time for the largest area was less than 20 min per scan. Smaller areas could be assessed with less reader time. CONCLUSION: We demonstrated that the LACS method is fast, responsive, and associated with radiographic and pain progression, and is appropriate for existing and future large studies of KOA.

Magnetic resonance imaging lesions are more severe and cartilage T2 relaxation time measurements are higher in isolated lateral compartment radiographic knee osteoarthritis than in isolated medial compartment disease - data from the Osteoarthritis Initiative.

OBJECTIVE: Isolated lateral compartment tibiofemoral radiographic osteoarthritis (IL-ROA) is an understudied form of knee osteoarthritis (OA). The objective of the present study was to characterize Magnetic Resonance Imaging (MRI) abnormalities and MR-T2 relaxation time measurements associated with IL-ROA and with isolated medial compartment ROA (IM-ROA) compared with knees without OA. METHOD: 200 case subjects with IL-ROA (Kellgren/Lawrence (K/L) grade≥2 and joint space narrowing (JSN) > 0 in the lateral compartment but JSN = 0 in the medial compartment) were randomly selected from the Osteoarthritis Initiative baseline visit. 200 cases with IM-ROA and 200 controls were frequency matched to the IL-ROA cases. Cases and controls were analyzed for odds of having a subregion with >10% cartilage area affected, with ≥25% bone marrow lesions (BML), with meniscal tear or maceration, and for association with cartilage T2 values. RESULTS: IL-ROA was more strongly associated with ipsilateral MRI knee pathologies than IM-ROA (IL-ROA: OR = 135.2 for size of cartilage lesion, 95% CI 42.7-427.4; OR = 145.4 for large size BML, 95% CI 41.5-509.5; OR = 176 for meniscal tears, 95% CI 59.8-517.7; IM-ROA: OR = 28.4 for size of cartilage lesion, 95% CI 14.7-54.7; OR = 38.1 for size of BML, 95% CI 12.7-114; OR = 37.0 for meniscal tears, 95% CI 12-113.6). Cartilage T2 values were higher in both tibial and medial femoral compartments in IL-ROA, but in IM-ROA were only significantly different from controls in the medial femur. CONCLUSION: IL-ROA knees show a greater prevalence and severity of MRI lesions and higher cartilage T2 values than IM-ROA knees compared with controls.

Baseline trabecular bone and its relation to incident radiographic knee osteoarthritis and increase in joint space narrowing score: directional fractal signature analysis in the MOST study.

PURPOSE: To explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score. METHODS: The Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren-Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL ≤ 1) at baseline were assessed for incident OA (KL ≥ 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders. RESULTS: Of 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales. CONCLUSION: Baseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.

Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women.

INTRODUCTION: Hip shape is a risk factor for the development of hip osteoarthritis (OA), and current methods to assess hip shape from radiographs are limited; therefore this study explored current and novel methods to assess hip shape. METHODS: Data from a prior case-control study nested in the Johnston County OA Project were used, including 382 hips (from 342 individuals). Hips were classified by radiographic hip OA (RHOA) status as RHOA cases (baseline Kellgren Lawrence grade [KLG] 0 or 1, follow-up [mean 6 years] KLG ≥ 2) or controls (KLG = 0 or 1 at both baseline and follow-up). Proximal femur shape was assessed using a 60-point model as previously described. The current analysis explored commonly used principal component analysis (PCA), as well as novel statistical methodologies suited to high dimension low sample size settings (Distance Weighted Discrimination [DWD] and Distance Projection Permutation [DiProPerm] hypothesis testing) to assess differences between cases and controls. RESULTS: Using these novel methodologies, we were able to better characterize morphologic differences by sex and race. In particular, the proximal femurs of African American women demonstrated significantly different shapes between cases and controls, implying an important role for sex and race in the development of RHOA. Notably, discrimination was improved with the use of DWD and DiProPerm compared to PCA. CONCLUSIONS: DWD with DiProPerm significance testing provides improved discrimination of variation in hip morphology between groups, and enables subgroup analyses even under small sample sizes.

Do persons with asymmetric hip pain or radiographic hip OA have worse pain and structure outcomes in the knee opposite the more affected hip? Data from the Osteoarthritis Initiative.

PURPOSE: To determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips. METHODS: We studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations. RESULTS: Knees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17). CONCLUSION: These findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

Brief Report: Cartilage Thickness Change as an Imaging Biomarker of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

OBJECTIVE: To investigate the association of cartilage thickness change over 24 months, as determined by magnetic resonance imaging (MRI), with knee osteoarthritis (OA) progression at 24-48 months. METHODS: This nested case-control study included 600 knees with a baseline Kellgren/Lawrence (K/L) grade of 1-3 from 600 Osteoarthritis Initiative (OAI) participants. Case knees (n = 194) had both medial tibiofemoral radiographic joint space loss (≥0.7 mm) and a persistent increase in the Western Ontario and McMaster Universities Osteoarthritis Index pain score (≥9 on a 0-100 scale) 24-48 months from baseline. Control knees (n = 406) included 200 with neither radiographic nor pain progression, 103 with radiographic progression only, and 103 with pain progression only. Medial and lateral femorotibial cartilage was segmented from sagittal 3T MRIs at baseline, 12 months, and 24 months. Logistic regression was used to assess the association of change in cartilage thickness, with a focus on the central medial femorotibial compartment, and OA progression. RESULTS: Central medial femorotibial compartment thickness loss was significantly associated with case status, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.6-2.3) (P < 0.0001). Association with case status reached P < 0.05 for both the central femur (OR 1.8 [95% CI 1.5-2.2]) and the central tibia (OR 1.6 [95% CI 1.3-1.9]). Lateral femorotibial compartment cartilage thickness loss, in contrast, was not significantly associated with case status. A reduction in central medial femorotibial compartment cartilage thickness was strongly associated with radiographic progression (OR 4.0 [95% CI 2.9-5.3]; P < 0.0001) and only weakly associated with pain progression (OR 1.3 [95% CI 1.1-1.6]; P < 0.01). CONCLUSION: Our findings indicate that loss of medial femorotibial cartilage thickness over 24 months is associated with the combination of radiographic and pain progression in the knee, with a stronger association for radiographic progression.

Knee joint subchondral bone structure alterations in active athletes: a cross-sectional case-control study.

OBJECTIVE: It has been shown that trabecular bone structure parameters extracted from radiographs known as fractal signature analysis (FSA) are able to predict structural outcomes such as radiographic osteoarthritis (OA) progression. Little is known about their involvement in early disease or about differences between subjects exposed to increased joint loading such as young active athletes compared to non-athletes. Aim was to compare horizontal and vertical dimensions of bone texture considering athlete status, gender, previous anterior cruciate ligament (ACL) surgery and age. DESIGN: Included were 685 patients of which 135 consecutive athletes (82% soccer players) 18-36 years old and 550 non-athletes controls in the same age range had knee radiography for assessment of subacute or chronic knee complaints. Regions of interest (ROI) were placed in the subchondral medial and lateral tibial plateaus. Fractal signatures were calculated in the horizontal and vertical dimensions. Curve fitting algorithms were applied taking into account all four risk factors in the same model adjusting for each other. RESULTS: For the horizontal dimensions significant differences were observed for gender (estimate (E) 0.098 (95% confidence interval(CI)) (-0.009, 0.008), P < .0001), previous ACL surgery (E -0.031, 95% CI (-0.043, -0.019), P < .0001) and highest age group (E -0.039, 95% CI (-0.048, -0.029), P < .0001). For vertical dimensions, significant differences were shown for athletes (E -0.012, 95% CI (-0.020, -0.004), P < .0001), gender (E 0.056, 95% CI (0.049, 0.062), P < .0001), and age range from 28 to 32 years (E -0.028, 95% CI (-0.037, -0.019), P < .0001). CONCLUSIONS: Trabecular bone structure differs between athletes and non-athletes, in regard to previous ACL surgery, gender and higher age.

Association of Physical Activity Measured by Accelerometer, Knee Joint Abnormalities, and Cartilage T2 Measurements Obtained From 3T Magnetic Resonance Imaging: Data From the Osteoarthritis Initiative.

OBJECTIVE: To study the cross-sectional association between physical activity measured with an accelerometer, structural knee abnormalities, and cartilage T2 values assessed with 3T magnetic resonance imaging (MRI). METHODS: We included 274 subjects from the Osteoarthritis Initiative cohort without definite radiographic osteoarthritis (Kellgren/Lawrence grades 0 and 1) and with at most mild pain, stiffness, and functional limitation in the study knee (Western Ontario and McMaster Universities Osteoarthritis Index scale 0-1), which had not limited their activity due to knee pain. Physical activity was measured over 7 days with an ActiGraph GT1M accelerometer. Subjects were categorized by quartile of physical activity based on the average daily minutes of moderate to vigorous physical activity (mv-PA). MRI images of the right knee (at 48-month visit) were assessed for structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) and for T2 relaxation times derived from segmented cartilage of 4 femorotibial regions and the patella. WORMS grades and T2 measurements were compared between activity quartiles using a linear regression model. Covariates included age, sex, body mass index, knee injury, family history of knee replacement, knee symptoms, hip and ankle pain, and daily wear time of the accelerometer. RESULTS: Higher mv-PA was associated with increased severity (P = 0.0087) and number of lesions of the medial meniscus (P = 0.0089) and with severity of bone marrow edema lesions (P = 0.0053). No association between cartilage lesions and mv-PA was found. T2 values of cartilage (loss, damage, and abnormalities) tended to be greater in the higher quartiles of mv-PA, but the differences were nonsignificant. CONCLUSION: In knees without radiographic osteoarthritis in subjects with no or mild knee pain, higher physical activity levels were associated with increases in meniscal and bone marrow edema pattern lesions.

A reference database of cartilage 3 T MRI T2 values in knees without diagnostic evidence of cartilage degeneration: data from the osteoarthritis initiative.

OBJECTIVE: 1) To establish a gender- and BMI-specific reference database of cartilage T2 values, and 2) to assess the associations between cartilage T2 values and gender, age, and BMI in knees without radiographic osteoarthritis or MRI-based (WORMS 0/1) evidence of cartilage degeneration. DESIGN: 481 subjects aged 45-65 years with Kellgren-Lawrence Scores 0/1 in the study knee were selected. Baseline morphologic cartilage 3T MRI readings (WORMS scoring) and T2 measurements (resolution = 0.313 mm × 0.446 mm) were performed in the medial and lateral femurs, medial and lateral tibias, and patella compartments. To create a reference database, a logarithmic transformation was applied to the data to obtain the 5th-95th percentile values for T2. RESULTS: Significant differences in mean cartilage T2 values were observed between joint compartments. Although females had slightly higher T2 values than males in a majority of compartments, the differences were only significant in the medial femur (P < 0.0001). A weak positive association was seen between age and T2 in all compartments, most pronounced in the patella (3.27% increase in median T2/10 years, P = 0.009). Significant associations between BMI and T2 were observed, most pronounced in the lateral tibia (5.33% increase in median T2/5 kg/m(2) increase in BMI, P < 0.0001), and medial tibia (4.81% increase in median T2 /5 kg/m(2) increase in BMI, P < 0.0001). CONCLUSIONS: This study established the first reference database of T2 values in a large sample of morphologically normal cartilage plates in knees without radiographic knee osteoarthritis (OA). While cartilage T2 values were weakly associated with age and gender, they had the highest correlations with BMI.

Association of cartilage degeneration with four year weight gain--3T MRI data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the effect of weight gain on progression of early knee morphologic abnormalities using magnetic resonance imaging (MRI) in a longitudinal study over 48 months. DESIGN: We studied the right knee of 100 subjects from the Osteoarthritis Initiative (OAI), selecting subjects aged ≥ 45 with osteoarthritis (OA) risk factors who demonstrated weight gain (minimum 5% increase in body mass index, BMI, n = 50) or no change in weight (BMI change < 2%, n = 50), frequency matched for age, gender, and baseline BMI. Baseline and 48 month knee MRI studies were scored for lesions using a modified whole organ MRI score (WORMS). Logistic regression models were used to compare the differences between the two groups. RESULTS: The odds of worsening maximum cartilage (11.3, 95%, CI 3.5-51.4) and meniscal WORMS (4.5, 95% CI 1.4-17.3) were significantly greater in the weight gain group compared to the no change group, in addition to the odds of worsening cartilage defects at the patella and average meniscal WORMS (P < 0.05). Odds of worsening average bone marrow edema pattern (BMEP) were significantly greater for the weight gain group compared to the no change cohort (P < 0.05). CONCLUSION: Our study demonstrated that weight gain is strongly associated with increased progression of cartilage degeneration in middle-aged individuals with risk factors for OA.

A new method to measure anatomic knee alignment for large studies of OA: data from the osteoarthritis initiative.

OBJECTIVE: To develop and validate a new and improved software method to rapidly determine femur-tibia angle (FTA). METHODS: Three readers, two skilled and one unskilled, without any formal medical training, measured FTA in 142 subjects from the Osteoarthritis Initiative (OAI). The reader reliability was assessed using the intra-class correlation coefficient (ICC), root mean square standard deviation (RMSSD), and Bland-Altman plots, comparing the existing and new FTA methods. Gender-specific linear regression assessed the relationship of FTA with the hip-knee-ankle angle (HKA). RESULTS: The ICC (RMSSD) for intra- and inter-reader reproducibility of the existing FTA method was 0.96 (0.77°) and 0.92 (1.38°), respectively, and for the new technique was 0.98 (0.25°) and 0.98 (0.37°), with similar results for all three readers. Bland-Altman 95% limits of agreement were greater than ±2° for the existing, and ±1° for the new method. The r-value for the relation of FTA to HKA was 0.68 and 0.72 for the existing and new methods, respectively. Varus (HKA ≤ -2°)/neutral (-2° < HKA < 2°)/valgus (HKA ≥ 2°) alignment based on predicted HKA agreed moderately with measured HKA (weighted kappa = 0.53), and had moderate sensitivity (73%) and specificity (84%) for varus malalignment. The new FTA was related to HKA using a linear equation with a slope of 0.98 and an offset of 4.0°. CONCLUSIONS: Since it is largely automated and uses unambiguous anatomical landmarks, the new method is highly reproducible and can be made on a standard posteroanterior (PA) knee radiograph by a relatively unskilled reader.