Summary Objective As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular ...contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. Design This was a longitudinal cohort study of adults aged 50–79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. Results Subjects ( N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) 95% confidence interval (CI) of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). Conclusions Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.
Summary Objective Role of intra-articular calcium crystals in osteoarthritis (OA) is unclear. Imaging modalities used to date for its evaluation have limitations in their ability to fully ...characterize intra-articular crystal deposition. Since Computed Tomography (CT) imaging provides excellent visualization of bones and calcified tissue, in this pilot project we evaluated the utility of CT scan in describing intra-articular calcium crystal deposition in the knees. Method We included 12 subjects with and four subjects without radiographic chondrocalcinosis in the most recent visit from the Multicenter Osteoarthritis (MOST) study, which is a longitudinal cohort of community-dwelling older adults with or at risk for knee OA. All subjects underwent CT scans of bilateral knees. Each knee was divided into 25 subregions and each subregion was read for presence of calcium crystals by a musculoskeletal radiologist. To assess reliability, readings were repeated 4 weeks later. Results CT images permitted visualization of 25 subregions with calcification within and around the tibio-femoral and patello-femoral joints in all 24 knees with radiographic chondrocalcinosis. Intra-articular calcification was seen universally including meniscal cartilage (most common site involved in 21/24 knees), hyaline cartilage, cruciate ligaments, medial collateral ligament and joint capsule. Readings showed good agreement for specific tissues involved with calcium deposition (kappa: 0.70, 95% CI 0.62–0.80). Conclusion We found CT scan to be a useful and reliable tool for describing calcium crystal deposition in the knee and therefore potentially for studying role of calcium crystals in OA. We also confirmed that “chondrocalcinosis” is a misnomer because calcification is present ubiquitously.
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.
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.
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.
BUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA.
To investigate the association between meniscal pathology and incident or enlarging bone marrow lesions (BML) in knee osteoarthritis.
The authors studied subjects from the Multicenter Osteoarthritis ...Study aged 50-79 years either with knee osteoarthritis or at high risk of the disease. Baseline and 30-months magnetic resonance images of knees (n=1344) were scored for subchondral BML. Outcome was defined as an increase in BML score in either the tibial or femoral condyle in medial and lateral compartments, respectively. The authors defined meniscal pathology at baseline as the presence of either meniscal lesions or meniscal extrusion. The risk of an increase in BML score in relation to meniscal status in the same compartment was estimated using a log linear regression model adjusted for age, sex, body mass index, physical activity level and mechanical axis. In secondary analyses the investigators stratified by ipsilateral tibiofemoral cartilage status at baseline and compartments with pre-existing BML.
The adjusted relative risk of incident or enlarging BML ranged from 1.8; 95% CI 1.3 to 2.3 for mild medial meniscal pathology to 5.0; 95% CI 3.2 to 7.7 for major lateral meniscal pathology (using no meniscal pathology in the same compartment as reference). Stratification by cartilage or BML status at baseline had essentially no effect on these estimates.
Knee compartments with meniscal pathology have a substantially increased risk of incident or enlarging subchondral BML over 30 months. Higher relative risks were seen in those with more severe and with lateral meniscal pathology.
Knee osteoarthritis (OA) is a risk factor for a decline in gait speed. Daily walking reduces the risk of developing slow gait speed and future persistent functional limitation. However, the ...protective role of walking intensity is unclear. We investigated the association of substituting time spent not walking, with walking at light and moderate-to-vigorous intensities for incident slow gait over 2-years, among people with or at high risk of knee OA.
We used baseline and 2-year follow-up data from the Multicenter Osteoarthritis (MOST) study (n = 1731) and the Osteoarthritis Initiative (OAI, n = 1925). Daily walking intensity was objectively assessed using accelerometer-enabled devices, and classified as; not walking (<1 steps/min), very-light (1–49 steps/min), light (50–100 steps/min), and moderate-to-vigorous (>100 steps/min). We defined slow gait during a 20-m walk, as <1 m/s and <1.2 m/s. Isotemporal substitution evaluated time-substitution effects on incident slow gait outcomes at 2-years.
Replacing 20 min/day of not walking with walking at a moderate-to-vigorous intensity, demonstrated small to moderate reductions in the risk of developing a gait speed <1.0 m/s (Relative Risk 95% confidence interval (CI); MOST = 0.51 0.27, 0.98, OAI = 0.21 0.04, 0.98), and <1.2 m/s (MOST = 0.73 0.53, 1.00, OAI = 0.65 0.36, 1.18). However, only risk reductions for <1.0 m/s met statistical significance. Replacing not walking with very-light or light intensity walking was not associated with the risk of developing slow gait outcomes.
When possible, walking at a moderate-to-vigorous intensity (>100 steps/min) may be best recommended in order to reduce the risk of developing critical slow gait speed among people with, or at high risk of knee OA.
Objective
To assess whether medial tibiofemoral joint space width (JSW) on 3‐dimensional (3‐D) standing computed tomography (SCT) correlates more closely with magnetic resonance imaging cartilage ...morphology (CM) and meniscal scores than does radiographic 2‐D JSW.
Methods
Participants in the Multicenter Osteoarthritis Study, who had standing fixed‐flexion posteroanterior knee radiographs, were recruited. Medial tibiofemoral 3‐D JSW on SCT and 2‐D JSW on fixed‐flexion radiographs were compared with medial tibiofemoral cartilage and meniscal morphology using the Whole‐Organ Magnetic Resonance Imaging Score (WORMS). Associations between the area of the articular surface with 3‐D JSW <2.5 mm on SCT, radiographic minimal 2‐D JSW, and the WORMS‐CM and meniscal scores were assessed using Spearman's rho.
Results
For the 19 participants included (33 knees), mean ± SD age was 66.9 ± 5.4 years, body mass index was 29.5 ± 4.4 kg/m2, 42.1% of participants were female, and the Kellgren/Lawrence grades were 0 (21.2%), 1 (36.4%), 2 (18.2%), and 3 (24.2%). The articular surface area with 3‐D JSW <2.5 mm on SCT correlated with WORMS‐CM scores for the central medial tibia (rs = 0.84, P < 0.001), central medial femur (rs = 0.60, P < 0.007), and posterior medial meniscal tear (rs = 0.39, P < 0.026), as did other cut points for 3‐D JSW. Correlations with radiographic minimal 2‐D JSW were −0.66, −0.52, and −0.40, respectively, differing from SCT only for tibial cartilage (P = 0.001).
Conclusion
Greater surface area with a low JSW, measured by SCT, correlates more strongly with the severity of tibial cartilage lesions, while correlating with medial femoral cartilage and meniscal damage to a similar extent as radiographic minimal JSW. SCT may enable valid stratification of participants in clinical trials, through quickly and inexpensively characterizing osteoarthritis features.
Summary 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 0-3. 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 BMI. Results 1094 knees were included in the study. Compared to knees without SHFP hyperintensity, those with SHFP hyperintensity had 1.2 (95% Confidence Interval, 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.
To determine the sex-specific relation of frontal plane alignment (FPA) to magnetic resonance imaging (MRI)-defined features of patellofemoral osteoarthritis, and also to tibiofemoral osteoarthritis ...and knee pain.
The Multicenter Osteoarthritis Study is cohort study comprised of individuals with or at risk of knee osteoarthritis. We determined the sex-specific dose–response relation of baseline FPA to MRI-defined patellofemoral and tibiofemoral structural worsening, and incident knee pain, over 7 years.
In women only, greater varus alignment was associated with medial patellofemoral osteophytes (risk ratio RR 1.7 95% CI 1.2, 2.6) and valgus with lateral patellofemoral osteophytes (RR 1.9 1.0, 3.6). In men, greater varus increased risk for medial tibiofemoral cartilage worsening (RR 1.7 1.1, 2.6), and valgus for lateral tibiofemoral cartilage worsening (RR 1.8 1.6, 2.2). In women, findings were similar for tibiofemoral cartilage, but varus also increased risk for medial bone marrow lesions BMLs (RR 2.2 1.6, 3.1) and medial osteophytes (RR 1.8 1.3, 2.5), and valgus for lateral BMLs (RR 3.3 2.2, 4.5) and osteophytes (RR 2.0 1.2, 3.2). Varus increased risk of incident pain in men (RR 1.7 1.4, 2.2) and women (RR 1.3 1.0, 1.6), valgus did so in men only (RR 1.5 1.1, 1.9).
FPA was associated with patellofemoral osteophyte worsening in women, though overall was more strongly associated with tibiofemoral than patellofemoral osteoarthritis feature worsening. FPA in women was more consistently associated with structural worsening, yet men had higher associations with incident pain.
Summary Objective Magnetic resonance imaging (MRI) has greater sensitivity to detect osteoarthritis (OA) damage than radiographs but it is uncertain which MRI findings in early OA are clinically ...important. We examined MRI abnormalities detected in knees without radiographic OA and their association with incident knee symptoms. Method Participants from the Multicenter Osteoarthritis Study (MOST) without frequent knee symptoms (FKS) at baseline were eligible if they also lacked radiographic features of OA at baseline. At 15 months, knees that developed FKS were defined as cases while control knees were drawn from those that remained without FKS. Baseline MRIs were scored at each subregion for cartilage lesions (CARTs); osteophytes (OST); bone marrow lesions (BML) and cysts. We compared cases and controls using marginal logistic regression models, adjusting for age, gender, race, body mass index (BMI), previous injury and clinic site. Results 36 case knees and 128 control knees were analyzed. MRI damage was common in both cases and controls. The presence of a severe CART ( P = 0.03), BML ( P = 0.02) or OST ( P = 0.02) in the whole knee joint was more common in cases while subchondral cysts did not differ significantly between cases and controls ( P > 0.1). Case status at 15 months was predicted by baseline damage at only two locations; a BML in the lateral patella ( P = 0.047) and at the tibial subspinous subregions ( P = 0.01). Conclusion In knees without significant symptoms or radiographic features of OA, MRI lesions of OA in only a few specific locations preceded onset of clinical symptoms and suggest that changes in bone play a role in the early development of knee pain. Confirmation of these findings in other prospective studies of knee OA is warranted.
Summary Objective Subchondral bone attrition (SBA) is defined as flattening or depression of the osseous articular surface. The causes of attrition are unknown, but remodeling processes due to ...chronic overload that are reflected as bone marrow edema-like lesions (BMLs) on magnetic resonance imaging (MRI) might predispose the subchondral bone to subsequent attrition. The aim of this study was to evaluate the cross-sectional and longitudinal association of BMLs with SBA in the same subregion of the knee. Design The Multicenter Osteoarthritis (MOST) study is a longitudinal observational study of individuals who have or are at high risk for knee osteoarthritis. Subjects with available baseline and 30-months follow-up MRI were included. Patients with a recent history of trauma or findings suggestive of post-traumatic bone marrow changes were excluded. Subchondral BMLs and SBA were scored semiquantitatively from 0 to 3 in 10 tibiofemoral subregions. We evaluated the association of prevalent BMLs at baseline with the presence of prevalent and incident SBA on a per-subregion basis using logistic regression. We also cross-sectionally evaluated the association of BML grade severity and presence of baseline SBA. Results One thousand and twenty-five knees were included. 8.9% of the analyzed knee subregions showed SBA present at baseline and 9.2% of subregions exhibited prevalent subchondral BMLs. The adjusted odds ratio (OR) for prevalent SBA for subregions with prevalent BMLs was 18.8 95% confidence intervals (CI) 15.9–22.4. A larger BML size was directly associated with an increased risk of prevalent SBA. 195 (2.2%) subregions exhibited incident SBA at follow-up. The adjusted OR for incident SBA was 5.3 95% CI 3.6–7.7 when compared to subregions without BMLs as the reference. Conclusions Prevalent and incident SBA is strongly associated with subchondral BMLs in the same subregion. One explanation for the presence and development of SBA is subchondral remodeling due to increased stress, which is reflected as BMLs on MRI.
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