Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Thigh muscle and fat volumes are associated with knee cartilage abnormalities and bone marrow edema-like lesions: data from the osteoarthritis initiative.

OBJECTIVE: To investigate the associations of thigh muscle and fat volumes with structural abnormalities on MRI related to knee osteoarthritis. MATERIALS AND METHODS: MRI studies of the thighs and knees from 100 individuals were randomly selected from the Osteoarthritis Initiative Cohort. Whole Organ MR Scoring (WORMS) and effusion-synovitis scoring were performed in all knee MRI. Thigh muscles, intermuscular fat, and subcutaneous fat were manually segmented in 15 consecutive MR thigh images. Radiographic Kellgren-Lawrence grades (KLG) were also obtained in all knee radiographs. Independent t-tests were used to investigate the associations between thigh muscle and fat volumes, and sex. Mixed-effects analyses were obtained to investigate the associations between thigh muscle and fat volumes, KLG, WOMAC pain score, cartilage and bone marrow WORMS, as well as effusion-synovitis scores. RESULTS: Women had higher subcutaneous fat volume than men (616.82 vs. 229.13 cm3, p < 0.01) and men had higher muscle volumes than women (p < 0.01). Quadriceps (coef = -2.15, p = 0.01) and vastus medialis (coef = -1.84, p = 0.03) volumes were negatively associated with the WORMS cartilage scores. Intermuscular fat volume (coef = 0.48, p = 0.01) was positively associated with WORMS bone marrow edema-like lesion (BMEL) scores. The quadriceps (coef = -0.99, p < 0.01) and hamstring (coef = -0.59, p = 0.01) volumes were negatively associated with WORMS BMEL scores. No evidence of an association was found between thigh muscle and fat volumes with KLG and effusion-synovitis grading (p > 0.05). CONCLUSION: Increased quadriceps and hamstring volumes were negatively associated with cartilage lesion and BMEL scores while no evidence of an association was found between thigh muscle and fat volumes, and radiographic knee osteoarthritis or effusion-synovitis grading.

Magnetic Resonance Imaging-Defined Osteoarthritis Features and Anterior Knee Pain in Individuals With, or at Risk for, Knee Osteoarthritis: A Multicenter Study on Osteoarthritis.

OBJECTIVE: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs. METHODS: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain. RESULTS: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7-14.6]), whole-knee joint effusion-synovitis (OR 4.7 [95% CI 1.3-16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0-7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3-4.0] and PR 1.9 [95% CI 1.1-3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5-4.7]) were associated with AKP. CONCLUSION: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP.

Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI).

BACKGROUND: Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years. METHODS: Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0-96) and subscores for cartilage (0-36), menisci (0-24), and bone marrow abnormalities and subchondral cyst-like lesions (0-18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0-100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade. RESULTS: Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL -6.9 [-11.6, -2.1], 0.005). CONCLUSIONS: Opioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.

Patterns of Change Over Time in Knee Bone Shape Are Associated with Sex.

BACKGROUND: Knee osteoarthritis (OA) is more common in females than in males; however, the biological mechanisms for the difference in sex in patients with knee OA are not well understood. Knee shape is associated with OA and with sex, but the patterns of change in the bone's shape over time and their relation to sex and OA are unknown and may help inform how sex is associated with shape and OA and whether the effect is exerted early or later in life.Questions/purposes (1) Does knee shape segregate stably into different groups of trajectories of change (groups of knees that share similar patterns of changes in bone shape over time)? (2) Do females and males have different trajectories of bone shape changes? (3) Is radiographic OA at baseline associated with trajectories of bone shape changes? METHODS: We used data collected from the NIH-funded Osteoarthritis Initiative (OAI) to evaluate a cohort of people aged 45 to 79 years at baseline who had either symptomatic knee OA or were at high risk of having it. The OAI cohort included 4796 participants (58% females; n = 2804) at baseline who either had symptomatic knee OA (defined as having radiographic tibiofemoral knee OA and answering positively to the question "have you had pain, aching or stiffness around the knee on most days for at least one month during the past 12 months") or were at high risk of symptomatic knee OA (defined as having knee symptoms during the prior 12 months along with any of the following: overweight; knee injury; knee surgery other than replacement; family history of total knee replacement for OA; presence of Heberden's nodes; daily knee bending activity) or were part of a small nonexposed subcohort. From these participants, we limited the eligible group to those with radiographs available and read at baseline, 2 years, and 4 years, and randomly selected participants from each OAI subcohort in a manner to enrich representation in the study of the progression and nonexposed subcohorts, which were smaller in number than the OA incidence subcohort. From these patients, we randomly sampled 473 knees with radiographs available at baseline, 2 years, and 4 years. We outlined the shape of the distal femur and proximal tibia on radiographs at all three timepoints using statistical shape modelling. Five modes (each mode represents a particular type of knee bone shape variation) were derived for the proximal tibia and distal femur's shape, accounting for 78% of the total variance in shape. Group-based trajectory modelling (a statistical approach to identify the clusters of participants following a similar progression of change of bone shape over time, that is, trajectory group) was used to identify distinctive patterns of change in the bone shape for each mode. We examined the association of sex and radiographic OA at baseline with the trajectories of each bone shape mode using a multivariable polytomous regression model while adjusting for age, BMI, and race. RESULTS: Knee bone shape change trajectories segregated stably into different groups. In all modes, three distinct trajectory groups were derived, with the mean posterior probabilities (a measure of an individual's probability of being in a particular group and often used to characterize how well the trajectory model is working to describe the population) ranging from 84% to 99%, indicating excellent model fitting. For most of the modes of both the femur and tibia, the intercepts for the three trajectory groups were different; however, the rates of change were generally similar in each mode. Females and males had different trajectories of bone shape change. For Mode 1 in the femur, females were more likely to be in trajectory Groups 3 (odds ratio 30.2 [95% CI 12.2 to 75.0]; p < 0.001) and 2 than males (OR 4.1 [95% CI 2.3 to 7.1]; p < 0.001); thus, females had increased depth of the intercondylar fossa and broader shaft width relative to epicondylar width compared with males. For Mode 1 in the tibia, females were less likely to be in trajectory Group 2 (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.01) than males (that is, knees of females were less likely to display superior elevation of tibial plateau or decreased shaft width relative to head width). Radiographic OA at baseline was associated with specific shape-change trajectory groups. For Mode 1 in the femur, knees with OA were less likely to be in trajectory Groups 3 (OR 0.4 [95% CI 0.2 to 0.8]; p = 0.008) and 2 (OR 0.6 [95% CI 0.3 to 1.0]; p = 0.03) than knees without OA; thus, knees with OA had decreased depth of the intercondylar fossa and narrower shaft width relative to epicondylar width compared with knees without OA. For Mode 1 in the tibia, knees with OA were not associated with trajectory. CONCLUSIONS: The shapes of the distal femur and proximal tibia did not change much over time. Sex and baseline knee radiographic OA status are associated with the trajectory of change in the bone's shape, suggesting that both may contribute earlier in life to the associations among trajectories observed in older individuals. Future studies might explore sex-related bone shape change earlier in life to help determine when the sex-specific shapes arise and also the degree to which these sex-related shapes are alterable by injury or other events. LEVEL OF EVIDENCE: Level III, prognostic study.

Evaluation of Chondrocalcinosis and Associated Knee Joint Degeneration Using MR Imaging: Data from the Osteoarthritis Initiative.

OBJECTIVES: To evaluate the ability of different MRI sequences to detect chondrocalcinosis within knee cartilage and menisci, and to analyze the association with joint degeneration. METHODS: Subjects with radiographic knee chondrocalcinosis (n = 90, age 67.7 ± 7.3 years, 50 women) were selected from the Osteoarthritis Initiative and matched to controls without radiographic chondrocalcinosis (n = 90). Visualization of calcium-containing crystals (CaC) was compared between 3D T1-weighted gradient-echo (T1GE), 3D dual echo steady-state (DESS), 2D intermediate-weighted (IW), and proton density (PD)-weighted fast spin-echo (FSE) sequences obtained with 3T MRI and correlated with a semiquantitative CaC score obtained from radiographs. Structural abnormalities were assessed using Whole-Organ MRI Score (WORMS) and logistic regression models were used to compare cartilage compartments with and without CaC. RESULTS: Correlations between CaC counts of MRI sequences and degree of radiographic calcifications were highest for GE (rT1GE = 0.73, P < 0.001; rDESS = 0.68, P < 0.001) compared to other sequences (P > 0.05). Meniscus WORMS was significantly higher in subjects with chondrocalcinosis compared to controls (P = 0.005). Cartilage defects were significantly more frequent in compartments with CaC than without (patella: P = 0.006; lateral tibia: P < 0.001; lateral femur condyle: P = 0.017). CONCLUSIONS: Gradient-echo sequences were most useful for the detection of chondrocalcinosis and presence of CaC was associated with higher prevalence of cartilage and meniscal damage. KEY POINTS: • Magnetic resonance imaging is useful for assessing burden of calcium-containing crystals (CaC). • Gradient-echo sequences are superior to fast spin echo sequences for CaC imaging. • Presence of CaC is associated with meniscus and cartilage degradation.

Semi-quantitative MRI biomarkers of knee osteoarthritis progression in the FNIH biomarkers consortium cohort - Methodologic aspects and definition of change.

BACKGROUND: To describe the scoring methodology and MRI assessments used to evaluate the cross-sectional features observed in cases and controls, to define change over time for different MRI features, and to report the extent of changes over a 24-month period in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium study nested within the larger Osteoarthritis Initiative (OAI) Study. METHODS: We conducted a nested case-control study. Cases (n = 406) were knees having both radiographic and pain progression. Controls (n = 194) were knee osteoarthritis subjects who did not meet the case definition. Groups were matched for Kellgren-Lawrence grade and body mass index. MRIs were acquired using 3 T MRI systems and assessed using the semi-quantitative MOAKS system. MRIs were read at baseline and 24 months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. We provide the definition and distribution of change in these biomarkers over time. RESULTS: Seventy-three percent of the cases had subregions with BML worsening (vs. 66 % in controls) (p = 0.102). Little change in osteophytes was seen over 24 months. Twenty-eight percent of cases and 10 % of controls had worsening in meniscal scores in at least one subregion (p < 0.001). Seventy-three percent of cases and 53 % of controls had at least one area with worsening in cartilage surface area (p < 0.001). More cases experienced worsening in Hoffa- and effusion synovitis than controls (17 % vs. 6 % (p < 0.001); 41 % vs. 18 % (p < 0.001), respectively). CONCLUSIONS: A wide range of MRI-detected structural pathologies was present in the FNIH cohort. More severe changes, especially for BMLs, cartilage and meniscal damage, were detected primarily among the case group suggesting that early changes in multiple structural domains are associated with radiographic worsening and symptomatic progression.

Semiquantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

OBJECTIVE: To determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild-to-moderate osteoarthritis (OA). METHODS: We undertook a nested case-control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and effusion-synovitis. RESULTS: The most parsimonious model included changes in cartilage thickness and surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8-fold (95% confidence interval [95% CI] 1.3-5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4-fold (95% CI 1.3-4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2-fold (95% CI 1.3-3.8) greater odds of being a case. Worsening effusion-synovitis and Hoffa-synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively). CONCLUSION: Twenty-four-month changes in cartilage thickness, cartilage surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease-modifying interventions for knee OA.

Diagnostic performance of 3D standing CT imaging for detection of knee osteoarthritis features.

OBJECTIVE: To determine the diagnostic performance of standing computerized tomography (SCT) of the knee for osteophytes and subchondral cysts compared with fixed-flexion radiography, using MRI as the reference standard. METHODS: Twenty participants were recruited from the Multicenter Osteoarthritis Study. Participants' knees were imaged with SCT while standing in a knee-positioning frame, and with postero-anterior fixed-flexion radiography and 1T MRI. Medial and lateral marginal osteophytes and subchondral cysts were scored on bilateral radiographs and coronal SCT images using the OARSI grading system and on coronal MRI using Whole Organ MRI Scoring. Imaging modalities were read separately with images in random order. Sensitivity, specificity and accuracy for the detection of lesions were calculated and differences between modalities were tested using McNemar's test. RESULTS: Participants' mean age was 66.8 years, body mass index was 29.6 kg/m(2) and 50% were women. Of the 160 surfaces (medial and lateral femur and tibia for 40 knees), MRI revealed 84 osteophytes and 10 subchondral cysts. In comparison with osteophytes and subchondral cysts detected by MRI, SCT was significantly more sensitive (93 and 100%; p < 0.004) and accurate (95 and 99%; p < 0.001 for osteophytes) than plain radiographs (sensitivity 60 and 10% and accuracy 79 and 94%, respectively). For osteophytes, differences in sensitivity and accuracy were greatest at the medial femur (p = 0.002). CONCLUSIONS: In comparison with MRI, SCT imaging was more sensitive and accurate for detection of osteophytes and subchondral cysts than conventional fixed-flexion radiography. Additional study is warranted to assess diagnostic performance of SCT measures of joint space width, progression of OA features and the patellofemoral joint.

Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker--longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative.

INTRODUCTION: Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). METHODS: A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). RESULTS: This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. CONCLUSION: Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.

Quantification of bone marrow lesion volume and volume change using semi-automated segmentation: data from the osteoarthritis initiative.

BACKGROUND: To determine the validity of a semi-automated segmentation of bone marrow lesions (BMLs) in the knee. METHODS: Construct validity of the semi-automated BML segmentation method was explored in two studies performed using sagittal intermediate weighted, turbo spine echo, fat-suppressed magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative. The first study (n = 48) evaluated whether tibia BML volume was different across Boston Leeds Osteoarthritis Knee Scores (BLOKS) for tibia BMLs (semiquantitative grades 0 to 3). In the second study (n = 40), we evaluated whether BML volume change was associated with changes in cartilage parameters. The knees in both studies were segmented by one investigator. We performed Wilcoxon signed-rank tests to determine if tibia BML volume was different between adjacent BLOKS BML scores and calculated Spearman correlation coefficients to assess the relationship between 2-year BML volume change and 2-year cartilage morphometry change (significance was p ≤ 0.05). RESULTS: BML volume was significantly greater between BLOKS BML score 0 and 1 (z = 2.85, p = 0.004) and BLOKS BML scores 1 and 2 (z = 3.09, p = 0.002). There was no significant difference between BLOKS BML scores 2 and 3 (z = -0.30, p = 0.77). Increased tibia BML volume was significantly related to increased tibia denuded area (Spearman r = 0.42, p = 0.008), decreased tibia cartilage thickness (Spearman r = -0.46, p = 0.004), increased femur denuded area (Spearman r = 0.35, p = 0.03), and possibly decreased femur cartilage thickness (Spearman r = -0.30, p = 0.07) but this last finding was not statistically significant. CONCLUSION: The new, efficient, and reliable semi-automated BML segmentation method provides valid BML volume measurements that increase with greater BLOKS BML scores and confirms previous reports that BML size is associated with longitudinal cartilage loss.

Bone marrow lesion volume reduction is not associated with improvement of other periarticular bone measures: data from the Osteoarthritis Initiative.

INTRODUCTION: We evaluated the associations between bone marrow lesion (BML) volume change and changes in periarticular bone mineral density (paBMD) as well as subchondral sclerosis to determine whether BML change is associated with other local bone changes. METHODS: The convenience sample comprised participants in the Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee radiographs and magnetic resonance images (MRIs) at the 24- and 48-month visits and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month visits. The right knee was assessed unless contraindicated for MRI. We used knee DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a semiautomated segmentation method. To focus on knees with only medial tibia BML changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume change was classified into three groups: BML regression (lowest quartile of medial tibial BML volume change), no-to-minimal change (middle two quartiles), and BML progression (highest quartile). We used proportional odds logistic regression models to evaluate the association between quartiles of changes in medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change. RESULTS: The sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with radiographic osteoarthritis, and participants with a mean age of 63.8 ± 9.3 years and mean body mass index of 29.8 ± 4.7 kg/m(2). We found an association between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95% confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had borderline statistical significance. The frequency of sclerosis progression in the medial tibia (n = 14) was greater among knees with BML progression or regression compared with knees without BML change (P = 0.01 and P = 0.04, respectively). CONCLUSION: BML regression and BML progression are characterized by concurrent increases in paBMD and sclerosis, which are characteristic of increased radiographic osteoarthritis severity. At least during 24 months, BML regression is not representative of improvement in other periarticular bone measures.

Lumbosacral transitional vertebrae: association with low back pain.

PURPOSE: To assess the prevalence and degree of lumbosacral transitional vertebrae (LSTV) in the Osteoarthritis Initiative (OAI) cohort, to assess whether LSTV correlates with low back pain (LBP) and buttock pain, and to assess the reproducibility of grading LSTV. MATERIALS & METHODS: Institutional review board approval was obtained, and informed consent documentation was approved for the study protocol. Standard standing pelvic radiographs that included the transverse processes of L5 were graded according to Castellvi classification of LSTV in 4636 participants (1992 men and 2804 women; aged 45-80 years) from the OAI cohort. These data were correlated with prevalence and severity of LBP and buttock pain. RESULTS: Prevalence of LSTV was 18.1% (841 of 4636), with a higher rate in men than in women (28.1% vs 11.1%, respectively; P<.001). Of the 841 individuals with LSTV, 41.72% were type I (dysplastic enlarged transverse process), 41.4% were type II (pseudoarticulation), 11.5% were type III (fusion), and 5.2% were type IV (one transverse process fused and one with pseudoarticulation). Of the participants without LSTV, 53.9% reported LBP, while the prevalence of LBP for types I, II, III, and IV was 46%, 73%, 40%, and 66%, respectively (P<.05, χ2 test). Types II and IV had higher prevalence and severity of LBP and buttock pain (P<.001). CONCLUSION: LSTV types II and IV positively correlate with prevalence and severity of LBP and buttock pain.

Association between measures of trochlear morphology and structural features of patellofemoral joint osteoarthritis on MRI: the MOST study.

The sulcus angle has been widely used in the literature as a measure of trochlear morphology. Recently, lateral trochlear inclination and trochlear angle have been reported as alternatives. The purpose of this study was to determine the association between measures of trochlear morphology and patellofemoral joint (PFJ) cartilage damage and bone marrow lesions (BMLs). Nine hundred seven knees were selected from the Multicenter Osteoarthritis Study, a cohort study of persons aged 50-79 years with or at risk for knee OA. Trochlear morphology was measured using lateral trochlear inclination, trochlear angle, and sulcus angle on axial MRI images; cartilage damage and BMLs were graded on MRI. We determined the association between quartiles of each trochlear morphology variable with the presence or absence of cartilage damage and BMLs in the PFJ using logistic regression. The strongest associations were seen with lateral trochlear inclination and lateral PFJ cartilage damage and BMLs, with knees in the lowest quartile (flattened lateral trochlea) having more than two times the odds of lateral cartilage damage and BMLs compared to those in the highest quartile (p < 0.0001). Lateral trochlear inclination may be the best method for assessment of trochlear morphology as it was strongly association with structural damage in the PFJ.

Subchondral cystlike lesions develop longitudinally in areas of bone marrow edema-like lesions in patients with or at risk for knee osteoarthritis: detection with MR imaging--the MOST study.

PURPOSE: To assess the association of prevalent bone marrow edema-like lesions (BMLs) and full-thickness cartilage loss with incident subchondral cyst-like lesions (SCs) in the knee to evaluate the bone contusion versus synovial fluid intrusion theories of SC formation. MATERIALS AND METHODS: The Multicenter Osteoarthritis study is a longitudinal study of individuals who have or are at risk for knee osteoarthritis. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. Magnetic resonance images were acquired at baseline and 30-month follow-up and read semiquantitatively by using the Whole-Organ Magnetic Resonance Imaging Score system. The tibiofemoral and patellofemoral joints were subdivided into 14 subregions. BMLs and SCs were scored from 0 to 3. Cartilage morphology was scored from 0 to 6. The association of prevalent BMLs and full-thickness cartilage loss with incident SCs in the same subregion was assessed by using logistic regression with mutual adjustment for both predictors. RESULTS: A total of 1283 knees were included. After adjustment for full-thickness cartilage loss, prevalent BMLs showed a strong and significant association with incident SCs in the same subregion, with an odds ratio of 12.9 (95% confidence interval [CI]: 8.9, 18.6). After adjustment for BMLs, prevalent full-thickness cartilage loss showed a significant but much less important association with incident SCs in the same subregion (odds ratio, 1.4; 95% CI: 1.0, 2.0). There was no apparent relationship between severity of full-thickness cartilage loss at baseline and incident SCs. CONCLUSION: Prevalent BMLs strongly predict incident SCs in the same subregion, even after adjustment for full-thickness cartilage loss, which supports the bone contusion theory of SC formation.

Meniscal pathology on MRI increases the risk for both incident and enlarging subchondral bone marrow lesions of the knee: the MOST Study.

OBJECTIVES: To investigate the association between meniscal pathology and incident or enlarging bone marrow lesions (BML) in knee osteoarthritis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Short tau inversion recovery and proton density-weighted fat suppressed sequences for the evaluation of osteoarthritis of the knee with a 1.0 T dedicated extremity MRI: development of a time-efficient sequence protocol.

Aim of this study was to develop a time-efficient sequence protocol for a 1.0 T dedicated MR system to be used for whole-organ scoring of osteoarthritis (OA). Thirty-four knees were examined using a protocol that included fat suppressed fast spin echo proton density weighted sequences (PDFS) in three planes plus a coronal STIR sequence. Two radiologists scored each knee by consensus for five OA features. In separate sessions, all knees were scored using three different combinations of sequences: (1) all four sequences (reference protocol, 16 min 31 s scanning time), (2) three PDFS sequences without STIR ("No STIR", 12 min 25 s scanning time) and (3) sagittal and axial PDFS sequences plus a coronal STIR sequence ("No PDFS", 11 min 49 s scanning time). Agreement of the readings using both subsets of sequences compared to the reference protocol was evaluated using weighted kappa statistics. kappa-coefficients showed good or excellent agreement for both sequence subsets in comparison to the reference protocol for all assessed features. kappa-coefficients for No PDFS/No STIR: bone marrow abnormalities (0.74/0.67), subarticular cysts (0.84/0.63), marginal osteophytes (0.77/0.71), menisci (0.75/0.79), tibial cartilage (0.71/0.78). Optimization of sequence protocols consisting of three sequences results in time savings and cost efficiency in imaging of knee OA without loss of information over a more time consuming protocol.

Multispectral analysis of bone lesions in the hands of patients with rheumatoid arthritis.

Quantitative measures of rheumatoid arthritis (RA) disease progression can provide valuable tools for evaluation of new treatments during clinical trials. In this study, a novel multispectral (MS) MRI analysis method is presented to quantify changes in bone lesion volume (DeltaBLV) in the hands of RA patients. Image registration and MS analysis were employed to identify MS tissue class transitions between two serial MRI exams. DeltaBLV was determined from MS class transitions between two time points. The following three classifiers were investigated: (a) multivariate Gaussian (MVG), (b) k-nearest neighbor (k-NN), and (c) K-means (KM). Unlike supervised classifiers (MVG, k-NN), KM, an unsupervised classifier, does not require labeled training data, resulting in potentially greater clinical utility. All MS estimates of DeltaBLV were linearly correlated (r(p)) with manual estimates. KM and k-NN estimates also exhibited a significant rank-order correlation (r(s)) with manual estimates. For KM, r(p) = 0.94 p < 0.0001, r(s) = 0.76 p = 0.002; for k-NN, r(p) = 0.86 p = 0.0001, r(s) = 0.69 p = 0.009; and for MVG, r(p) = 0.84 p = 0.0003, r(s) = 0.49 p = 0.09. Temporal classification rates were as follows: for KM, 90.1%; for MVG, 89.5%; and for k-NN, 86.7%. KM matched the performance of k-NN, offering strong potential for use in multicenter clinical trials. This study demonstrates that MS tissue class transitions provide a quantitative measure of DeltaBLV.