[show abstract][hide abstract] ABSTRACT: 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 inter-relationships 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).
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).
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]=1.23-1.83), and JSN progression (OR=1.27, 95%CI=1.11-1.46). 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=1.55-7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume.
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.
Arthritis research & therapy 09/2013; 15(5):R112. · 4.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression.
To determine whether vitamin D supplementation reduces symptom and structural progression of knee OA.
A 2-year randomized, placebo-controlled, double-blind, clinical trial involving 146 participants with symptomatic knee OA (mean age, 62.4 years [SD, 8.5]; 57 women [61%], 115 white race [79%]). Patients were enrolled at Tufts Medical Center in Boston between March 2006 and June 2009.
Participants were randomized to receive either placebo or oral cholecalciferol, 2000 IU/d, with dose escalation to elevate serum levels to more than 36 ng/mL.
Primary outcomes were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0-20: 0, no pain; 20, extreme pain), and cartilage volume loss measured by magnetic resonance imaging. Secondary end points included physical function, knee function (WOMAC function scale, 0-68: 0, no difficulty; 68, extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width.
Eighty-five percent of the participants completed the study. Serum 25-hydroxyvitamin D levels increased by a mean 16.1 ng/mL (95% CI, 13.7 to 18.6) in the treatment group and by a mean 2.1 mg/mL (95% CI, 0.5 to 3.7) (P < .001) in the placebo group. Baseline knee pain was slightly worse in the treatment group (mean, 6.9; 95% CI, 6.0 to 7.7) than in the placebo group (mean, 5.8; 95% CI, 5.0 to 6.6) (P = .08). Baseline knee function was significantly worse in the treatment group (mean, 22.7; 95% CI, 19.8 to 25.6) than in the placebo group (mean, 18.5; 95% CI, 15.8 to 21.2) (P = .04). Knee pain decreased in both groups by a mean -2.31 (95% CI, -3.24 to -1.38) in the treatment group and -1.46 (95% CI, -2.33 to -0.60) in the placebo group, with no significant differences at any time. The percentage of cartilage volume decreased by the same extent in both groups (mean, -4.30; 95% CI, -5.48 to -3.12 vs mean, -4.25; 95% CI, -6.12 to -2.39) (P = .96). There were no differences in any of the secondary clinical end points. CONCLUSION AND RELEVANCE: Vitamin D supplementation for 2 years at a dose sufficient to elevate 25-hydroxyvitamin D plasma levels to higher than 36 ng/mL, when compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic knee OA.
clinicaltrials.gov Identifier: NCT00306774.
JAMA The Journal of the American Medical Association 01/2013; 309(2):155-62. · 29.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry. DESIGN: 158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D fast imaging with steady state precession (FISP) sequence for trabecular morphometry in the same session as the OAI 3 T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score. RESULTS: Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (P < 0.01), trabecular number (P < 0.01), and thickness (P = 0.02), and lower trabecular spacing (P < 0.01). CONCLUSIONS: Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.
Osteoarthritis and Cartilage 08/2012; 20(12):1519-1526. · 4.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the relationship of medial proximal tibial periarticular areal bone mineral density (paBMD) and trabecular morphometry and determined whether these bone measures differed across radiographic medial joint space narrowing (JSN) scores.
482 participants of the Osteoarthritis Initiative (OAI) Bone Ancillary Study had knee dual X-ray absorptiometry (DXA) and trabecular bone 3T magnetic resonance imaging (MRI) exams assessed at the same visit. Medial proximal tibial paBMD was measured on DXA and apparent trabecular bone volume fraction (aBV/TV), thickness (aTb.Th), number (aTb.N), and spacing (aTb.Sp) were determined from MR images. Radiographs were assessed for medial JSN scores (0-3). We evaluated associations between medial paBMD and trabecular morphometry. Whisker plots with notches of these measures versus medial JSN scores were generated and presented.
Mean age was 63.9 (9.2) years, BMI 29.6 (4.8) kg/m(2), and 53% were male. The Spearman correlation coefficients between DXA-measured medial paBMD and aBV/TV was 0.61 [95% confidence interval (CI) 0.55-0.66]; between paBMD and aTb.Th was 0.38 (95%CI 0.30-0.46); paBMD and aTb.N was 0.65 (95%CI 0.60-0.70); paBMD and aTb.Sp was -0.65 (95%CI -0.70 to -0.59). paBMD and the trabecular metrics were associated with medial JSN scores.
The moderate associations between periarticular trabecular bone density and morphometry and their relationship with greater severity of knee OA support hypotheses of remodeling and/or microscopic compression fractures in the natural history of OA. Longitudinal studies are needed to assess whether knee DXA will be a predictor of OA progression. Further characterization of the periarticular bone in OA utilizing complementary imaging modalities will help clarify OA pathophysiology.
Osteoarthritis and Cartilage 03/2012; 20(7):686-93. · 4.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this narrative year in review of clinical studies was to highlight a few publications related to obesity and weight loss, physical activity, and synovitis as well as disease modifying interventions that were published between September 2010 and September 2011. This year clinical research highlighted the extent to which obesity and osteoarthritis (OA) are impacting quality of life among adults in the United States and that reducing excessive body weight or becoming more physically active may be beneficial. In addition to weight loss and physical activity and synovitis, research over the past year has highlighted the diverse methods being pursued for structural modification interventions. In addition to chondroitin sulfate there were interesting preliminary findings that meniscal implants and joint distractions may modify OA progression.
Osteoarthritis and Cartilage 03/2012; 20(3):197-200. · 4.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate associations of varus thrust and varus static alignment with pain in patients with knee osteoarthritis (OA).
This was a cross-sectional study of participants from a randomized controlled trial of vitamin D treatment for knee OA. Participants were video recorded while walking and scored for presence of varus thrust. Static alignment was measured on standard posteroanterior knee radiographs. Pain questions from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire were used to assess symptoms. We calculated means for total WOMAC pain in relation to varus thrust and static varus alignment (i.e., corrected anatomic alignment<178 degrees). Ordinal logistic regressions were performed, with responses on individual WOMAC pain questions as the outcomes and varus thrust and varus alignment as the predictors.
There were 82 participants, 60% of whom were female. The mean±SD age was 65.1±8.5 years, and the mean±SD body mass index was 30.2±5.4 kg/m2. The mean total WOMAC pain score was 6.3 versus 3.9, respectively, in those with versus without definite varus thrust (P=0.007) and 5.0 versus 4.2 in those with versus without varus alignment (P=0.36). Odds ratios for pain with walking and standing were 4.7 (95% confidence interval 1.8-11.9) and 5.5 (95% confidence interval 2.2-14.2), respectively, in those with and those without definite varus thrust. There were no significant associations between varus alignment and responses to individual WOMAC pain questions. Sensitivity analyses suggested that varus classified using a more stringent definition might have been associated with pain on walking and standing.
In patients with knee OA, varus thrust, and possibly varus static alignment, were associated with pain, specifically during weight-bearing activities. Treatment of varus thrust (e.g., via bracing or gait modification) may lead to improvement of symptoms.
[show abstract][hide abstract] ABSTRACT: Bone marrow lesions (BMLs), common osteoarthritis-related magnetic resonance imaging findings, are associated with osteoarthritis progression and pain. However, there are no articles describing the use of 3-dimensional quantitative assessments to explore the longitudinal relationship between BMLs and hyaline cartilage loss. The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume, and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage.
107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis. An 'index' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity. Subsequently, each knee was evaluated in four regions: index femur, index tibia, non-index femur, and non-index tibia. Approximate BML volume, the product of three linear measurements, was calculated for each BML within a region. Cartilage parameters in the index tibia and femur were measured based on manual segmentation.
BML volume changes by region were: index femur (median [95% confidence interval of the median]) 0.1 cm3 (-0.5 to 0.9 cm3), index tibia 0.5 cm3 (-0.3 to 1.7 cm3), non-index femur 0.4 cm3 (-0.2 to 1.6 cm3), and non-index tibia 0.2 cm3 (-0.1 to 1.2 cm3). Among 44 knees with full thickness cartilage loss, baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area (r = 0.63, p< 0.002) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area (r = 0.48 p< 0.002).
Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes. Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss.
[show abstract][hide abstract] ABSTRACT: In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers' experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability.
The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement).
With the exception of inter-rater reliability for tibial cartilage area (kappa=0.36) and tibial osteophytes (kappa=0.49); and intra-rater reliability for tibial BML number of lesions (kappa=0.54), Hoffa-synovitis (kappa=0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near-perfect agreement (0.81-1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%.
MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness.
Osteoarthritis and Cartilage 05/2011; 19(8):990-1002. · 4.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite a growing body of Magnetic Resonance Imaging (MRI) literature in osteoarthritis (OA), there is little uniformity in its diagnostic application. We envisage in the first instance the definition requiring further validation and testing in the research setting before considering implementation/feasibility testing in the clinical setting. The objective of our research was to develop an MRI definition of structural OA.
We undertook a multistage process consisting of a number of different steps. The intent was to develop testable definitions of OA (knee, hip and/or hand) on MRI. This was an evidence driven approach with results of a systematic review provided to the group prior to a Delphi exercise. Each participant of the steering group was allowed to submit independently up to five propositions related to key aspects in MRI diagnosis of knee OA. The steering group then participated in a Delphi exercise to reach consensus on which propositions we would recommend for a definition of structural OA on MRI. For each round of voting, ≥60% votes led to include and ≤20% votes led to exclude a proposition. After developing the proposition one of the definitions developed was tested for its validity against radiographic OA in an extant database.
For the systematic review we identified 25 studies which met all of our inclusion criteria and contained relevant diagnostic measure and performance data. At the completion of the Delphi voting exercise 11 propositions were accepted for definition of structural OA on MRI. We assessed the diagnostic performance of the tibiofemoral MRI definition against a radiographic reference standard. The diagnostic performance for individual features was: osteophyte C statistic=0.61, for cartilage loss C statistic=0.73, for bone marrow lesions C statistic=0.72 and for meniscus tear in any region C statistic=0.78. The overall composite model for these four features was a C statistic=0.59. We detected good specificity (1) but less optimal sensitivity (0.46) likely due to detection of disease earlier on MRI.
We have developed MRI definition of knee OA that requires further formal testing with regards their diagnostic performance (especially in datasets of persons with early disease), before they are more widely used. Our current analysis suggests that further testing should focus on comparisons other than the radiograph, that may capture later stage disease and thus nullify the potential for detecting early disease that MRI may afford. The propositions are not to detract from, nor to discourage the use of traditional means of diagnosing OA.
Osteoarthritis and Cartilage 05/2011; 19(8):963-9. · 4.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Anterior cruciate ligament (ACL) tears are known to be a risk factor for incident knee osteoarthritis (OA). At the present time, it is unknown whether an incidental ACL tear in those with established knee OA alters the pattern of synovial joint damage. Therefore, our aim was to assess whether ACL tears in persons with knee OA are associated with specific patterns of cartilage loss, meniscal degeneration, and bone marrow lesion (BML) location. We included 160 participants from the progression subcohort of the Osteoarthritis Initiative (OAI) Study, an ongoing 4-year, multicenter study, focusing on knee OA. Regional cartilage morphometry measures including cartilage volume (mm(3)), denuded area, normalized cartilage volume, bone surface area, as well as location of meniscal pathology and BMLs in index knees on the same side were compared between those with and without ACL tears. Of the 160 subjects (51% women, age 62.1 (±9.9), BMI 30.3 (±4.7) kg/m(2)), 14.4% had an ACL tear. After adjusting for age, BMI and gender participants with ACL tears had significantly greater cartilage volume in the posterior lateral femur (P = 0.04) and the central medial tibia (0.001) compared to those without ACL tears. Normalized cartilage volume was not different between those with and without ACL tears. In addition, individuals with ACL tears had significantly larger bone surface areas in the medial tibia (P = 0,006), the central medial tibia (P = 0.008), the posterior lateral femur (P = 0.004), and the posterior medial femur (P = 0.04). Furthermore, participants with ACL tears showed significantly more meniscal derangement in the lateral posterior horn (P = 0.019) and significantly more BMLs in the lateral femur (P = 0.0025). We found clear evidence of predominant lateral tibiofemoral involvement, with OA-associated findings on MRI, including increased denuded area and bone surface area, BMLs, and meniscal derangement in knees of individuals with ACL tears compared to those without.
Rheumatology International 01/2011; 32(5):1197-208. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Changes in weight-bearing subchondral bone are central to osteoarthritis (OA) pathophysiology. Using MR, knee trabecular bone is typically assessed in the axial plane, however partial volume artifacts limit the utility of MR methods for femorotibial compartment subchondral bone analysis. Oblique-coronal acquisitions may enable direct visualization and quantification of the expected increases in femorotibial subchondral trabecular bone.
MR acquisition parameters were first optimized at 3 Tesla. Thereafter, five volunteers underwent axial and coronal exams of their right knee. Each image series was evaluated visually and quantitatively. An anatomically standardized region-of-interest was placed on both the medial and lateral tibial plateaus of all coronal slices containing subchondral bone. Mean and maximum marrow signal was measured, and "bone signal" was calculated.
The MR acquisition had spatial resolution 0.2 × 0.2 × 1.0 mm and acquisition time 10.5 min. The two asymptomatic knees exhibited prominent horizontal trabeculae in the tibial subchondral bone, while the one confirmed OA knee had disorganized subchondral bone and absent horizontal trabeculae. The subchondral bone signal was 8-14% higher in both compartments of the OA knee than the asymptomatic knees.
The weight-bearing femorotibial subchondral trabecular bone can be directly visualized and changes quantified in the coronal-oblique plane. Qualitative and quantitative assessments can be performed using the resultant images and may provide a method to discriminate between the healthy and OA knees. These methods should enable a quantitative evaluation of the role of weight-bearing subchondral bone in the natural history of knee OA to be undertaken.