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).

Osteoarthritis Bone Marrow Lesions.

Assessment and treatment of Bone Marrow Lesions (BMLs) could ultimately make step changes to the lives of people with osteoarthritis (OA). We here review the imaging and pathological characteristics of OA-BMLs, their differential diagnosis and measurement, and cross-sectional and longitudinal associations with pain and OA structural progression. We discuss how biomechanical and cellular factors may contribute to BML pathogenesis, and how pharmacological and non-pharmacological interventions that target BMLs might reduce pain and OA structural progression. We critically appraise semiquantitative and quantitative methods for assessing BMLs, and their potential utilities for identifying people at risk of symptomatic and structural OA progression, and evaluating treatment responses. New interventions that target OA-BMLs should both confirm their importance, and reduce the unacceptable burden of OA.

Evaluating the structural effects of intra-articular sprifermin on cartilage and non-cartilaginous tissue alterations, based on sqMRI assessment over 2 years.

OBJECTIVE: Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment. DESIGN: Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5 mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30 µg or 100 µg or placebo every 6 (q6mo) or 12 months. 1.5- or 3 T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening. RESULTS: 549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100 µg q6mo vs placebo; mean DSM (95% confidence interval [CI]) -0.6 (-1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100 µg q6mo vs placebo; mean DSM (95% CI) -0.2 (-0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis. CONCLUSIONS: Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined.

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.

Safety, tolerability and efficacy of intra-articular Progenza in knee osteoarthritis: a randomized double-blind placebo-controlled single ascending dose study.

BACKGROUND: Cell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG. METHODS: We conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40-65 years with symptomatic Kellgren-Lawrence grade 1-3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months. RESULTS: The study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events [143/169 (84.6%)] were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p ≤ 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm3, 95% CI 13.56 mm3, 199.37 mm3, p = 0.028). CONCLUSION: When administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG's potential for disease modification in OA. Trial registration ANZCTR, ACTRN12615000439549. Date registered: 7th May 2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368355.

Changes in the structural features of osteoarthritis in a year of weight loss.

OBJECTIVE: In patients undergoing bariatric surgery or medical management for obesity, we assessed whether those experiencing substantial weight loss had changes in innervated knee structures or in cartilage. METHODS: Severely obese patients (body mass index (BMI) ≥35) with knee pain on most days were seen before bariatric surgery or medical weight management and at 1-year follow-up. Examinations included 3T MRI acquired at both time points for semi-quantitative scoring of bone marrow lesions (BML), synovitis, cartilage damage, and for quantitative measurement of cartilage thickness. Association of ≥20% vs <20% weight loss with change in semi-quantitative scores was evaluated using linear mixed-effects models, and that with cartilage thickness change used non-parametric and parametric methods. Sensitivity analyses tested different thresholds for weight loss, weight loss as a continuous measure, examined those with and without bariatric surgery, and with worse osteoarthritis (OA). RESULTS: 75 subjects (median age 49 years, 92% women) were included. At baseline, 61 subjects (81%) had Kellgren and Lawrence (KL) grade >0, and 16 (21%) had KL grade ≥3; 69 (92%) had cartilage damage. For BML, synovitis, and cartilage damage, the majority of knees had change in semi-quantitative scores of 0, and there was no difference between those with and without ≥20% weight loss. Similarly, in terms of cartilage thickness loss, in 14 of 16 sub-regions thickness loss was not associated with weight loss. Sensitivity analyses showed similar findings. CONCLUSION: In middle-aged persons with mostly mild radiographic OA, structural features changed little over a year and weight loss was not associated with effects on structural changes.

Relation of meniscus pathology to prevalence and worsening of patellofemoral joint osteoarthritis: the Multicenter Osteoarthritis Study.

OBJECTIVE: To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later. METHOD: Individuals from a prospective cohort of individuals aged 50-79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA. RESULTS: Relative to knees without lateral meniscal pathology at baseline, those with grades 3-4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 [95% CI: 1.1-2.7) and (1.7 [1.2-2.5]), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1-2 (0.6 [0.4-0.9]) and 3-4 (0.7 [0.5-1.0]) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later. CONCLUSION: Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ.

Is superolateral Hoffa's fat pad hyperintensity a marker of local patellofemoral joint disease? - The MOST study.

PURPOSE: To determine the relation of superolateral Hoffa's fat pad (SHFP) hyperintensity to cartilage damage and bone marrow lesions (BMLs) in the patellofemoral joint (PFJ) and tibiofemoral joint (TFJ). METHODS: We used data from the 60 and 84-month study visits from the Multicenter Osteoarthritis (MOST) study. SHFP hyperintensity and Hoffa-synovitis were graded from 0 to 3. Cartilage damage and BMLs were scored in the PFJ and TFJ. Structural damage was defined as: any cartilage damage, full-thickness cartilage damage and any BML. Worsening structural damage was defined as any increase in cartilage and BML scores. Logistic regression was used to determine the relation of SHFP hyperintensity and Hoffa-synovitis (>0) to structural damage, adjusting for age, sex and body mass index (BMI). RESULTS: 1,094 knees were included in the study. Compared to knees without SHFP hyperintensity, those with SHFP hyperintensity had 1.2 (95% Confidence Interval (CI), 1.1-1.4), 1.7 (1.3-2.3) and 1.6 (1.3-1.9) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the lateral PFJ respectively, and 1.1 (1.0-1.2), 1.3 (1.0-1.8), and 1.2 (1.0-1.4) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the medial PFJ. SHFP hyperintensity was associated with worsening BMLs in the medial PFJ (RR: 1.4 (1.0-1.9)). In general, there was no relation between SHFP hyperintensity and TFJ outcomes. Hoffa-synovitis was associated both cross-sectionally and longitudinally with structural damage, regardless of definition, in all compartments. CONCLUSION: SHFP hyperintensity may be a local marker of PFJ structural damage.

Knee tissue lesions and prediction of incident knee osteoarthritis over 7 years in a cohort of persons at higher risk.

OBJECTIVE: Among high risk individuals, whether knee lesions in tissues involved in osteoarthritis (OA) can improve prediction of knee OA is unclear. We hypothesized that models predicting (1) incident osteophytes and (2) incident osteophytes and joint space narrowing can be improved by including symptoms or function, and further improved by lesion status. DESIGN: In Osteoarthritis Initiative (OAI) participants with normal knee X-rays, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci. Cox proportional hazards models were used to develop risk prediction models for risk of each outcome. Nested models (increasingly larger baseline covariable sets) were compared using likelihood ratio tests and Schwarz Bayesian Information Criterion (SBC). Model discrimination used receiver operating characteristic (ROC) curves and area under the curve (AUC). RESULTS: In 841 participants [age 59.6, body mass index (BMI) 26.7, 55.9% women] over up to 7 years follow-up, each larger set improved prediction (+hand OA, injury, surgery, activities; +symptoms/function). Prediction was further improved by including cartilage damage both compartments, BMLs both compartments, meniscal tear, meniscal extrusion, sum of lesion types, number of subregions with cartilage damage, number of subregions with BMLs, and (concurrently) subregion number with cartilage damage, subregion number with BMLs, and meniscal tear. AUCs were ≥0.80 for both outcomes for number of subregions with cartilage damage and the combined model. CONCLUSIONS: Among persons at higher risk for knee OA with normal X-rays, MRI tissue lesions improved prediction of mild as well as moderate disease. These findings support that disease onset is likely occurring during the "high-risk" period and encourage a reorientation of approach.

Varus thrust during walking and the risk of incident and worsening medial tibiofemoral MRI lesions: the Multicenter Osteoarthritis Study.

OBJECTIVE: To determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over 2 years in older adults with or at risk for osteoarthritis (OA). METHOD: Subjects from the Multicenter Osteoarthritis Study (MOST) were studied. Varus thrust was visually assessed from high-speed videos of forward walking trials. Baseline and two-year MRIs were acquired from one knee per subject and read for cartilage loss and BMLs. Logistic regression with generalized estimating equations was used to estimate the odds of incident and worsening cartilage loss and BMLs, adjusting for age, sex, race, body mass index (BMI), and clinic site. The analysis was repeated stratified by varus, neutral, and valgus alignment. RESULTS: 1007 participants contributed one knee each. Varus thrust was observed in 29.9% of knees. Knees with thrust had 2.17 [95% CI: 1.51, 3.11] times the odds of incident medial BML, 2.51 [1.85, 3.40] times the odds of worsening medial BML, and 1.85 [1.35, 2.55] times the odds of worsening medial cartilage loss. When stratified by alignment, varus knees also had significantly increased odds of these outcomes. CONCLUSION: Varus thrust observed during walking is associated with increased odds of incident and worsening medial BMLs and worsening medial cartilage loss. Increased odds of these outcomes persist in varus-aligned knees.

Comparison between semiquantitative and quantitative methods for the assessment of knee synovitis in osteoarthritis using non-enhanced and gadolinium-enhanced MRI.

OBJECTIVE: To compare different semiquantitative and quantitative methods using both non-enhanced and gadolinium-enhanced MRI techniques for the assessment of synovitis in knee osteoarthritis (OA). METHODS: Knees with end-stage clinical OA in patients undergoing total knee replacement surgery were included in this cross-sectional study. MRI was performed on all knees. Standard non-enhanced and gadolinium-enhanced sequences were acquired. Using non-enhanced MRI, we semiquantitatively assessed two features widely used as surrogates for synovitis: effusion-synovitis and Hoffa-synovitis. Using gadolinium-enhanced sequences, we semiquantitatively assessed synovial thickness. We quantitatively evaluated the total synovial volume on the gadolinium-enhanced sequences as well. We assessed the correlations of effusion-synovitis and Hoffa-synovitis with synovial thickness and volume, applying Spearman correlation analysis. The diagnostic performance of both synovitis features on non-enhanced MRI was assessed using synovial thickness on gadolinium-enhanced MRI as the reference. RESULTS: A total of 104 subjects (one knee per subject) were included. Correlations of effusion-synovitis with synovial thickness and volume were r = 0.41 and r = 0.43 (P < .001) r = 0.32 and r = 0.39 (P < .0001). CONCLUSION: Using synovial thickness assessed on gadolinium-enhanced sequences as the reference, effusion-synovitis showed superior correlations and sensitivity. Effusion-synovitis should be preferred over Hoffa-synovitis as a surrogate marker for synovial thickening, in studies of knee OA for which gadolinium-enhanced sequences are not available.

Changes in patellofemoral and tibiofemoral joint cartilage damage and bone marrow lesions over 7 years: the Multicenter Osteoarthritis Study.

OBJECTIVES: To investigate changes in cartilage damage and bone marrow lesions (BMLs) on MRI in the patellofemoral and tibiofemoral joints (TFJs) over 7 years. METHODS: The Multicenter Osteoarthritis (MOST) Study is a cohort study of persons aged 50-79 years at baseline with or at high risk for knee osteoarthritis (OA). Knees were eligible for the current study if they had knee MRI (1.0T) assessed for cartilage damage and BMLs at the baseline and 84-month visits. Knees were categorized as having MRI-detected structural damage (cartilage and BMLs) isolated to the patellofemoral joint (PFJ), isolated to the TFJ, mixed or no damage at baseline and 84-months. We determined the changes in PFJ and TFJ structural damage over 7 years and used logistic regression to assess the relation of baseline compartment distribution to incident isolated PFJ, isolated TFJ and mixed damage. RESULTS: Among 339 knees that had full-thickness cartilage loss isolated to the PFJ or TFJ at baseline, only 68 (20.1%) developed full-thickness cartilage loss in the other compartment while 271 (79.9%) continued to only have the initial compartment affected. Compared to knees without full-thickness cartilage damage (n = 582), those with isolated TFJ and PFJ full-thickness cartilage damage had 2.7 (1.5, 4.9) and 5.8 (3.6, 9.6) times the odds of incident mixed full-thickness cartilage damage, respectively. Similar results were seen when using other definitions of MRI-defined structural damage. CONCLUSIONS: Most knees with structural damage at baseline do not develop it in the other compartment. Knees that develop mixed structural damage are more likely to start with it isolated to the PFJ.

Magnetic resonance imaging of Hoffa's fat pad and relevance for osteoarthritis research: a narrative review.

OBJECTIVE: To give an illustrative overview of Hoffa's fat pad pathology with a radiologic emphasis on the anatomy, on technical considerations, and on imaging differential diagnoses in the context of osteoarthritis (OA) imaging research. DESIGN: A PubMed database search including only English literature and covering a 20 year period was performed. The search was based on but no limited to the query terms "Hoffa", "Hoffa's fat pad" or "infrapatellar fat pad (IPFP)" in combination with "synovitis", "OA", and "magnetic resonance imaging (MRI)". The literature search yielded 289 publications that were screened for relevance; additional references were included when these were considered of importance. RESULTS: Several anatomic variants and pathologic conditions may be encountered when assessing Hoffa's fat pad including tumors and tumor-like lesions such as osteochondroma, tenosynovial giant cell tumor (TGCT) (and pigmented nodular synovitis) and arthrofibrosis, traumatic changes including contusions and anatomic variants such as recesses. The latter may be accountable for differences in cross-sectional area or volume changes over time. Signal changes are commonly used in OA research as surrogate markers for synovitis but are non-specific findings. CONCLUSIONS: Quantitative approaches to evaluate 3D parameters of Hoffa's fat pad are increasingly applied and their role in regard to structural progression and clinical manifestations of disease needs to be further elucidated. In applying such approaches, knowledge of the detailed anatomy and potential pitfalls that may be a result of anatomical variants, inflammatory disease manifestations and additional diverse pathologies encountered seems to be paramount.

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.

Baseline radiographic osteoarthritis and semi-quantitatively assessed meniscal damage and extrusion and cartilage damage on MRI is related to quantitatively defined cartilage thickness loss in knee osteoarthritis: the Multicenter Osteoarthritis Study.

OBJECTIVES: To provide a comprehensive simultaneous relation of various semiquantitative knee OA MRI features as well as the presence of baseline radiographic osteoarthritis (OA) to quantitative longitudinal cartilage loss. METHODS: We studied Multicenter OA Study (MOST) participants from a longitudinal observational study that included quantitative MRI measurement of cartilage thickness. These subjects also had Whole Organ MRI Score (WORMS) scoring of cartilage damage, bone marrow lesions (BMLs), meniscal pathology, and synovitis, as well as baseline radiographic evaluation for Kellgren and Lawrence (KL) grading. Knee compartments were classified as progressors when exceeding thresholds of measurement variability in normal knees. All potential risk factors of cartilage loss were dichotomized into "present" (score ≥2 for cartilage, ≥1 for others) or "absent". Differences in baseline scores of ipsi-compartmental risk factors were compared between progressor and non-progressor knees by multivariable logistic regression, adjusting for age, sex, body mass index, alignment axis (degrees) and baseline KL grade. Odds ratios (OR) and 95% CIs were calculated for medial femorotibial compartment (MFTC) and lateral femorotibial compartment (LFTC) cartilage loss. Cartilage loss across both compartments was studied using Generalized Estimating Equations. RESULTS: 196 knees of 196 participants were included (age 59.8 ± 6.3 years [mean ± SD], BMI 29.5 ± 4.6, 62% women). For combined analyses of MFTC and LFTC, baseline factors related to cartilage loss were radiographic OA (KL grade ≥2: aOR 4.8 [2.4-9.5], cartilage damage (aOR 2.3 [1.2-4.4])), meniscal damage (aOR 3.9 [2.1-7.4]) and extrusion (aOR 2.9 [1.6-5.3]), all in the ipsilateral compartment, but not BMLs or synovitis. CONCLUSION: Baseline radiographic OA and semiquantitatively (SQ) assessed MRI-detected cartilage damage, meniscal damage and extrusion, but not BMLs or synovitis is related to quantitatively measured ipsi-compartmental cartilage thinning over 30 months.

Severe radiographic knee osteoarthritis--does Kellgren and Lawrence grade 4 represent end stage disease?--the MOST study.

OBJECTIVE: To determine what MRI-detectable osteoarthritis features that are not visualized on radiography demonstrate progression longitudinally in Kellgren and Lawrence (KL) grade 4 knees. METHODS: We studied subjects from the Multicenter Osteoarthritis Study who had KL grade 4 knees at baseline and had baseline and 30-month MRI. Cartilage damage, bone marrow lesions (BMLs), meniscal damage, synovitis (signal changes in Hoffa fat pad), and effusion (fluid equivalent signal in the joint cavity) were semiquantitatively scored using the Whole Organ MRI Score (WORMS) system in five subregions of the medial and lateral tibiofemoral (TF) compartments. Analysis was performed for the compartment showing bone-on-bone appearance ("index") on radiograph and also for the other TF compartment of the same knee. Synovitis and effusion were assessed for the whole knee. Changes in scores at follow-up were noted for each feature. For cartilage and BML, within-grade changes were also recorded. RESULTS: 140 subjects (164 knees) were included (50% women, mean age 66.0 ± 8.6 years, mean BMI 30.4 ± 5.1 kg/m(2)). Longitudinally, 51 index compartments (34%) showed an increase in the sum of cartilage scores from all subregions. In the other compartment, 25% showed an increase in the sum score for cartilage damage. For BMLs in the index compartment, 50 knees (33%) showed an increase in maximum score and 32 (21%) showed a decrease. Meniscal status mostly remained stable. Effusion worsened in 36 knees (25%) and improved in 13 knees (9%). Synovitis worsened in 14 knees (10%) and improved in six knees (4%). CONCLUSION: In KL grade 4 knees, MRI-detected cartilage loss and fluctuation of BMLs, effusion, and synovitis occurred frequently over a 30-month period.

External knee adduction and flexion moments during gait and medial tibiofemoral disease progression in knee osteoarthritis.

OBJECTIVE: Test the hypothesis that greater baseline peak external knee adduction moment (KAM), KAM impulse, and peak external knee flexion moment (KFM) during the stance phase of gait are associated with baseline-to-2-year medial tibiofemoral cartilage damage and bone marrow lesion progression, and cartilage thickness loss. METHODS: Participants all had knee OA in at least one knee. Baseline peak KAM, KAM impulse, and peak KFM (normalized to body weight and height) were captured and computed using a motion analysis system and six force plates. Participants underwent MRI of both knees at baseline and 2 years later. To assess the association between baseline moments and baseline-to-2-year semiquantitative cartilage damage and bone marrow lesion progression and quantitative cartilage thickness loss, we used logistic and linear regressions with generalized estimating equations (GEE), adjusting for gait speed, age, gender, disease severity, knee pain severity, and medication use. RESULTS: The sample consisted of 391 knees (204 persons): mean age 64.2 years (SD 10.0); BMI 28.4 kg/m(2) (5.7); 156 (76.5%) women. Greater baseline peak KAM and KAM impulse were each associated with worsening of medial bone marrow lesions, but not cartilage damage. Higher baseline KAM impulse was associated with 2-year medial cartilage thickness loss assessed both as % loss and as a threshold of loss, whereas peak KAM was related only to % loss. There was no relationship between baseline peak KFM and any medial disease progression outcome measures. CONCLUSION: Findings support targeting KAM parameters in an effort to delay medial OA disease progression.

Imaging atlas for eligibility and on-study safety of potential shoulder adverse events in anti-NGF studies (Part 3).

Despite promising results, the U.S. Food and Drug Administration (FDA) put on hold trials assessing anti-nerve growth factor (a-NGF) compounds due to concerns over accelerated rates of OA progression. The mechanism of these events is unclear but joint adverse events were observed particularly in patients using a-NGFs in combination with non-steroidal anti-inflammatory drugs (NSAIDs), suggesting that the significantly greater analgesic effect of these separate classes of drugs prompted patients to permit increased joint load without experiencing the usual pain that would limit joint stress. Development of a-NGF drugs is continuing with stringent safety criteria included in future trials as a-NGF therapies offer potential as the first new class of analgesics in many years. Potential imaging joint safety findings and exclusionary criteria for eligibility for the large weight bearing joints were presented in parts I and II of this atlas. The shoulder as a non-weight bearing joint is likely to be less affected by increased loading due to efficacious pain reduction. However, it remains prone to degeneration especially due to concomitant rotator cuff pathology and previous trauma and inflammatory disorders. This third part of the atlas illustrates imaging findings relevant for eligibility and potential joint safety findings such as osteonecrosis, incidental findings such as large cystic lesions, inflammatory disorders, bone marrow disorders and metastases.

Increased risk for radiographic osteoarthritis features in young active athletes: a cross-sectional matched case-control study.

OBJECTIVE: Prevalence data on radiographic osteoarthritis (ROA) in young active athletes is sparse. Aim was to assess in a matched case-control design the frequency of ROA in an athlete population and whether athlete status, gender, previous anterior cruciate ligament (ACL) surgery and age increase the odds for ROA. DESIGN: 135 consecutive athletes (82% soccer players) 18-36 years old and 550 non-athletes aged-matched controls had knee radiography (Lyon-Schuss protocol) for assessment of subacute or chronic knee complaints. Patients with acute trauma or fractures were excluded. Radiographs were graded according to the Kellgren-Lawrence and OARSI grading schemes. In addition, medial and lateral intercondylar notch osteophytes were scored. We used logistic regression model to assess the association of ROA and specific radiographic OA features with athlete status, prior ACL surgery, gender and age, adjusting for each other. RESULTS: 19.4% of patients were 18-22 years old, 26.4% were 23-27, 22.6% were 28-32, and 31.5% were 33-36 years old. 18.7% were female and 8.8% had previous ACL surgery. 8.5% had ROA and 6.0% had evidence of JSN. The adjusted odds ratios (aOR) for ROA were 2.8 (95% confidence interval 1.4, 5.5) for athletes, 7.0 (3.5, 13.9) for previous ACL surgery and 3.3 (1.2, 9.0) for age range 32-36. Athlete status significantly increased odds for tibiofemoral osteophytes [aOR 2.9 (1.6, 5.4)] and comparably for notch osteophytes [aOR 2.3 (1.1, 4.7)]. CONCLUSIONS: Athlete status, higher age and previous ACL surgery increase the risk of ROA with surgery being the strongest risk factor.

Progression of cartilage damage and meniscal pathology over 30 months is associated with an increase in radiographic tibiofemoral joint space narrowing in persons with knee OA--the MOST study.

PURPOSE: To determine the association of MRI-assessed worsening of tibiofemoral cartilage damage, meniscal damage, meniscal extrusion, separately and together, with progression of radiographic joint space narrowing (JSN). METHOD AND MATERIALS: The Multicenter Osteoarthitis Study (MOST) Study is a cohort study of subjects with or at risk for knee osteoarthritis (OA). Knees with radiographic OA Kellgren-Lawrence grade 2 at baseline and with baseline and 30-month 1.0 T MRIs were selected for reading using the WORMS system for cartilage damage, meniscal damage, and meniscal extrusion. The association of worsening of cartilage damage, meniscal damage, and/or meniscal extrusion with increases in the JSN was performed using logistic regression. RESULTS: A total of 276 knees (one per subject) were included (women 68.5%, mean age 62.9 ± 7.8, mean body mass index (BMI) 30.2 ± 5.0). Worsening of each MRI feature was associated with any increase in JSN (P < 0.01). Worsening of cartilage damage was more frequently observed than worsening of meniscal damage and extrusion, and was significantly associated with both slow and fast progression of JSN. An increasing risk of JSN worsening was associated with increasing number of worsening MRI features (P for trend < 0.0001). CONCLUSION: Worsening of tibiofemoral cartilage damage, meniscal damage, and meniscal extrusion are independent predictors of JSN progression in the same compartment. Worsening of cartilage damage is more frequently observed in JSN when compared to meniscal worsening. A strong cumulative effect on JSN progression is observed for worsening of more than one MRI feature.