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Subchondral bone trabecular integrity predicts and changes concurrently with radiographic and magnetic resonance imaging-determined knee osteoarthritis progression.

ABSTRACT: To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression.Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters.Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA (P < 0.01 for 24 months), 24-month change in tibial (P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW (P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated (P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months.BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials.

SUBMITTER: Kraus VB

PROVIDER: S-EPMC4152231 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Subchondral bone trabecular integrity predicts and changes concurrently with radiographic and magnetic resonance imaging-determined knee osteoarthritis progression.

Kraus Virginia Byers VB Feng Sheng S Wang ShengChu S White Scott S Ainslie Maureen M Graverand Marie-Pierre Hellio Le MHL Brett Alan A Eckstein Felix F Hunter David J DJ Lane Nancy E NE Taljanovic Mihra S MS Schnitzer Thomas T Charles H Cecil HC

Arthritis and rheumatism 20130701 7

<h4>Objective</h4>To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression.<h4>Methods</h4>Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic reso ...[more]

PMID: 23576116

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Project description:OBJECTIVES:To assess whether initial or 12-18-month change in magnetic resonance imaging (MRI) subchondral bone texture is predictive of radiographic knee osteoarthritis (OA) progression over 36 months. METHODS:This was a nested case-control study including 122 knees/122 participants in the Osteoarthritis Initiative (OAI) Bone Ancillary Study, who underwent MRI optimised for subchondral bone assessment at either the 30- or 36-month and 48-month OAI visits. Case knees (n = 61) had radiographic OA progression between the 36- and 72-month OAI visits, defined as ? 0.7 mm minimum medial tibiofemoral radiographic joint space (minJSW) loss. Control knees (n = 61) without radiographic OA progression were matched (1:1) to cases for age, sex, body mass index and initial medial minJSW. Texture analysis was performed on the medial femoral and tibial subchondral bone. We assessed the association of texture features with radiographic progression by creating a composite texture score using penalised logistic regression and calculating odds ratios. We evaluated the predictive performance of texture features for predicting radiographic progression using c-statistics. RESULTS:Initial (odds ratio [95% confidence interval] = 2.13 [1.41-3.40]) and 12- 18-month change (3.76 [2.04-7.82]) texture scores were significantly associated with radiographic OA progression. Combinations of texture features were significant predictors of radiographic progression using initial (c-statistic [95% confidence interval] = 0.65 [0.64-0.65], p = 0.003) and 12-18-month change (0.68 [0.68-0.68], p < 0.001) data. CONCLUSIONS:Initial and 12-18-month changes in MRI subchondral bone texture score were significantly associated with radiographic progression at 36 months, with better predictive performance for 12-18-month change in texture. These results suggest that texture analysis may be a useful biomarker of subchondral bone in OA. KEY POINTS:• Subchondral bone MRI texture analysis is a promising knee osteoarthritis imaging biomarker. • In this study, subchondral bone texture was associated with knee osteoarthritis progression. • This demonstrates predictive and concurrent validity of MRI subchondral bone texture analysis. • This method may be useful in clinical trials with interventions targeting bone.

Project description:ObjectivesTo evaluate the reliability and validity of measuring subchondral trabecular biomarkers in "conventional" intermediate-weighted (IW) MRI sequences and to assess the predictive value of biomarker changes for predicting near-term symptomatic and structural progressions in knee osteoarthritis (OA).MethodsFor this study, a framework for measuring trabecular biomarkers in the proximal medial tibia in the "conventional" IW MRI sequence was developed. The reliability of measuring these biomarkers (trabecular thickness [cTbTh], spacing [cTbSp], connectivity density [cConnD], and bone-to-total volume ratio [cBV/TV]) was evaluated in the Bone Ancillary Study (within the Osteoarthritis Initiative [OAI]). The validity of these measurements was assessed by comparing to "apparent" biomarkers (from high-resolution steady-state MRI sequence) and peri-articular bone marrow density (BMD, from dual-energy X-ray absorptiometry). The association of these biomarker changes from baseline to 24 months (using the Reliable Change Index) with knee OA progression was studied in the FNIH OA Biomarkers Consortium (within the OAI). Pain and radiographic progression were evaluated by comparing baseline WOMAC pain score and radiographic joint space width with the 24-to-48-month scores/measurements. Associations between biomarker changes and these outcomes were studied using logistic regression adjusted for the relevant covariates.ResultsWith acceptable reliability, the cTbTh and cBV/TV, but not cTbSp or cConnD, were modestly associated with the "apparent" biomarkers and peri-articular BMD (β: 1.10 [95% CI: 0.45-1.75], p value: 0.001 and β: 3.69 [95% CI: 2.56-4.83], p value: < 0.001, respectively). Knees with increased cTbTh had higher (OR: 1.44 [95% CI: 1.03-2.02], p value: 0.035) and knees with decreased cTbTh (OR: 0.69 [95% CI: 0.49-0.95], p value: 0.026) or decreased cBV/TV (OR: 0.67 [95% CI: 0.48-0.93], p value: 0.018) had lower odds of experiencing OA pain progression over the follow-ups.ConclusionsMeasurement of certain "conventional" MRI-based subchondral trabecular biomarkers has high reliability and modest validity. Though modest, there are significant associations between these biomarker changes and knee OA pain progression up to 48-month follow-up.Key points• Despite the lower spatial resolution than what is required to accurately study the subchondral trabecular microstructures, the "conventional" IW MRI sequences may retain adequate information that allows quantification of trabecular microstructure biomarkers. • Subchondral trabecular biomarkers obtained from "conventional" IW MRI sequences (i.e., cTbTh, cTbSp, and cBV/TV) are reliable and valid measures of trabecular microstructure changes compared to those from "apparent" trabecular biomarkers (from the FISP MRI sequence) and peri-articular BMD (from DXA). • Increased trabecular thickness and bone-to-total ratio (cTbTh and cBV/TV, obtained from "conventional" IW MRI sequences) from baseline to 24-month visits may be associated with higher odds of knee OA pain progression over 48 months of follow-up.

Project description:BackgroundOsteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation.Materials and methodsThe type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.ResultsIn both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011).ConclusionSerum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.Level of evidenceLevel III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.

Project description:BackgroundSubchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA.MethodsThe preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters.ResultsAt both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region.ConclusionCyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Dataset Information

Subchondral bone trabecular integrity predicts and changes concurrently with radiographic and magnetic resonance imaging-determined knee osteoarthritis progression.

Publications

Subchondral bone trabecular integrity predicts and changes concurrently with radiographic and magnetic resonance imaging-determined knee osteoarthritis progression.

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