Minimum Joint Space Width Research Articles

Exploring the differences between radiographic joint space width and MRI cartilage thickness changes using data from the IMI-APPROACH cohort.

Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods. The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2years in medial JSW (ΔJSWmed), minimum JSW (ΔJSWmin), and medial femorotibial cartilage thickness (ΔMFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6months, and 1 and 2years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee-specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models. Correlations between ΔMFTC and ΔJSWmed and ΔJSWmin were statistically significant (p < 0.004) but weak (R < 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations. While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion.

Relationship of early postoperative perceived leg length discrepancy to the progression of osteoarthritis in the contralateral hip after unilateral total hip arthroplasty-a retrospective cohort study using propensity score matching.

[Purpose] This study aimed to identify the relationship between the early postoperative perceived leg length discrepancy after unilateral total hip arthroplasty and the progression of osteoarthritis in the contralateral hip. [Participants and Methods] This was a retrospective cohort study of 65 patients who underwent primary unilateral total hip arthroplasty for bilateral hip osteoarthritis. The minimum joint space width of the contralateral hip was measured preoperatively. The change in minimum joint space width one year postoperatively compared with preoperatively was measured. At three weeks postoperatively, patients were divided into the perceived and non-perceived leg length discrepancy groups using the block test. Patients with a perceived leg length discrepancy of 2 mm or more and less than 2 mm were grouped into the perceived and non-perceived leg length discrepancy groups, respectively. Before and after propensity score matching, the change in minimum joint space width between the two groups from the preoperative period to one year postoperatively was compared. [Results] In the pre-propensity matching sample, there was no significant difference in the change in minimum joint space width between the two groups. In the post-propensity matching sample, the change in minimum joint space width in the perceived leg length discrepancy group was significantly larger than that in the non-perceived leg length discrepancy group. [Conclusion] The early postoperative perceived leg length discrepancy after unilateral total hip arthroplasty may affect the progression of osteoarthritis in the contralateral hip.

Artificial intelligence in osteoarthritis: repair by knee joint distraction shows association of pain, radiographic and immunological outcomes.

Knee joint distraction (KJD) has been associated with clinical and structural improvement and SF marker changes. The current objective was to analyse radiographic changes after KJD using an automatic artificial intelligence-based measurement method and relate these to clinical outcome and SF markers. Twenty knee osteoarthritis patients were treated with KJD in regular care. Radiographs and WOMAC were collected before and ∼1 year post-treatment. SF was aspirated before, during and after treatment; biomarker levels were assessed by immunoassay. Radiographs were analysed to obtain compartmental minimum and standardized joint space width (JSW), Kellgren-Lawrence (KL) grades, compartmental joint space narrowing (JSN) scores, and osteophytosis and sclerosis scores. Results were analysed for the most affected compartment (MAC) and least affected compartment. Radiographic changes were analysed using the Wilcoxon signed rank test for categorical and paired t-test for continuous variables. Linear regression was used to calculate associations between changes in JSW, WOMAC pain and SF markers. Sixteen patients could be evaluated. JSW, KL and JSN improved in around half of the patients, significant only for MAC JSW (P < 0.05). MAC JSW change was positively associated with WOMAC pain change (P < 0.04). Greater monocyte chemoattractant protein 1 (MCP-1) and lower TGFβ-1 increases were significantly associated with changes in MAC JSW (P < 0.05). MCP-1 changes were positively associated with WOMAC pain changes (P < 0.05). Automatic radiographic measurements show improved joint structure in most patients after KJD in regular care. MAC JSW increased significantly and was associated with SF biomarker level changes and even with improvements in pain as experienced by these patients.

Statistical modeling: Assessing the anatomic variability of knee joint space width

Population-based knee joint space width (JSW) assessments are promising for the prevention and early diagnosis of osteoarthritis. This study aimed to establish the statistical shape and alignment model (SSAM) of knee joints for assessing anatomic variation in knee JSW in the healthy Chinese male population. CT scans of asymptomatic knee joints of healthy male participants (n = 107) were collected for manual segmentation to create mesh samples. The as-scanned positional error was reduced by a standard processing flow of deformable mesh registration. Principal component analysis (PCA) was performed to create a tibiofemoral SSAM that was trained on all mesh samples. The anatomic variability of the JSW in the healthy Chinese male population was then assessed using the SSAM with regression analysis and 3D analysis by color-coded mapping. Almost all PCA modes had a linear influence on the anatomic variation of the medial and lateral JSW. The JSW variability within the SSAM was mainly explained by mode 1 (45.1 % of variation), demonstrating that this mode had the greatest influence on JSW variation. 3D assessment of the JSW showed that the minimum medial JSW varied from 2.76 to 3.23 mm, and its site shifted a short distance on the medial tibial plateau. The root-mean-square fitting and generalization errors of the SSAM were below 1 mm. This study will benefit the design and optimization of prosthetic devices, and may be applicable to the prevention and early diagnosis of osteoarthritis.

Pain Sensitization and Neuropathic Pain-like Symptoms Associated with Effectiveness of Exercise Therapy in Patients with Hip and Knee Osteoarthritis.

Pain sensitization and neuropathic pain-like symptoms are some of the common pain symptoms in patients with lower limbs, including hip and knee, osteoarthritis (HOA/KOA). Exercise therapy has been the first-line treatment; however, the effects differ for each patient. This prospective cohort study investigated the relationship between the effectiveness of exercise therapy and pretreatment characteristics (radiologic severity, pain sensitization, and neuropathic pain-like symptoms) of patients with HOA/KOA. We assessed the pain intensity using a numerical rating scale (NRS) before and after 12 weeks of exercise therapy in patients with HOA/KOA (n = 101). Before treatment, the Kellgren–Lawrence (K-L) grade; minimum joint space width (mJSW); pressure pain threshold (PPT) and temporal summation of pain (TSP) at the affected joint, tibia, and forearm; Central Sensitization Inventory-9; and painDETECT questionnaire (PDQ) were assessed. Cluster analysis was based on the pretreatment NRS and change in NRS with exercise therapy to identify the subgroups of pain reduction. The pretreatment characteristics of each cluster were compared. According to the results of the cluster analyses, patients in cluster 1 had severe pain that did not improve after exercise therapy, patients in cluster 2 had severe pain that improved, and those in cluster 3 had mild pain that improved. The patients in cluster 1 exhibited lower PPT at all measurement sites, higher TSP at the affected joint, and higher PDQ scores than those in other clusters. There was no difference in the K-L grade and mJSW among the clusters. The subgroup with severe pain and pain sensitization or neuropathic pain-like symptoms at pretreatment, even with mild joint deformity, may have difficulty in achieving improvement in pain after 12 weeks of exercise therapy. These findings could be useful for prognosis prediction and for planning exercise therapy and combining with other treatment.

Fully Automatic Knee Joint Segmentation and Quantitative Analysis for Osteoarthritis from Magnetic Resonance (MR) Images Using a Deep Learning Model.

BackgroundWe aimed to develop and evaluate a deep learning-based method for fully automatic segmentation of knee joint MR imaging and quantitative computation of knee osteoarthritis (OA)-related imaging biomarkers.Material/MethodsThis retrospective study included 843 volumes of proton density-weighted fat suppression MR imaging. A convolutional neural network segmentation method with multiclass gradient harmonized Dice loss was trained and evaluated on 500 and 137 volumes, respectively. To assess potential morphologic biomarkers for OA, the volumes and thickness of cartilage and meniscus, and minimal joint space width (mJSW) were automatically computed and compared between 128 OA and 162 control data.ResultsThe CNN segmentation model produced reasonably high Dice coefficients, ranging from 0.948 to 0.974 for knee bone compartments, 0.717 to 0.809 for cartilage, and 0.846 for both lateral and medial menisci. The OA-related biomarkers computed from automatic knee segmentation achieved strong correlation with those from manual segmentation: average intraclass correlations of 0.916, 0.899, and 0.876 for volume and thickness of cartilage, meniscus, and mJSW, respectively. Volume and thickness measurements of cartilage and mJSW were strongly correlated with knee OA progression.ConclusionsWe present a fully automatic CNN-based knee segmentation system for fast and accurate evaluation of knee joint images, and OA-related biomarkers such as cartilage thickness and mJSW were reliably computed and visualized in 3D. The results show that the CNN model can serve as an assistant tool for radiologists and orthopedic surgeons in clinical practice and basic research.

Increased Joint Space Narrowing After Arthroscopic Partial Meniscectomy: Data From the Osteoarthritis Initiative

Background: Arthroscopic partial meniscectomy (APM) is widely performed and remains an important therapeutic option for patients with a meniscal tear. However, it is debated whether or not APM accelerates the progression of osteoarthritis (OA) in the long term. Purpose/Hypothesis: The purpose was to compare the progression of OA measured by the change in tibiofemoral joint space width (JSW)—a quantitative measure of OA radiographic severity—across 3 groups with a midterm follow-up: (1) patients undergoing APM; (2) those with a meniscal tear treated nonoperatively; and (3) those without a tear. We hypothesized that the reduction in JSW would be greatest in patients undergoing APM and least in those patients without a tear. Study Design: Cohort study; Level of evidence, 3. Methods: Using the Osteoarthritis Initiative cohort, a total of 144 patients were identified that underwent APM with at least 12 months of follow up and without previous knee surgery. Those with a meniscal tear who did not have APM (n = 144) and those without a tear (n = 144) were matched to patients who had APM by sex, age, Kellgren-Lawrence (KL) grade, and follow up time. Participants underwent magnetic resonance imaging at baseline. Knee radiographs to assess JSW were collected annually or biannually. The change in minimum medial compartment JSW was calculated using a validated automated method. A piecewise linear mixed effects model was constructed to examine the relationship between JSW decline over time and treatment group—adjusting for age, body mass index, smoking status, KL grade, and baseline JSW. Results: All groups had comparable baseline JSW—ranging from 4.33 mm to 4.38 mm. The APM group had a rate of JSW decline of −0.083 mm/mo in the first 12 months and −0.014 mm/mo between 12 and 72 months. The rate of JSW decline in the APM group was approximately 27 times greater in the first 12 months than that in the nonsurgical group (−0.003 mm/mo) and 5 times greater than that in the no tear group (−0.015 mm/mo); however, there was no significant difference between groups for 12 to 72 months (nonsurgical group: −0.009 mm/mo; no tear group: −0.010 mm/mo). The adjusted JSW in the APM group was 4.38 mm at baseline and decreased to 2.57 mm at 72 months; the JSW in the nonsurgical group declined from 4.31 mm to 3.73 mm, and in the no tear group it declined from 4.33 mm to 3.54 mm. There was a statistically significant difference in JSW change between baseline and 72 months for the APM group compared with the other groups (P < .001), but not between the nonsurgical and no tear groups (P = .12). Conclusion: In the first postoperative year, APM results in a faster rate of joint space narrowing compared with knees undergoing nonsurgical management of meniscal tears. Thereafter, there are comparable rates of OA progression regardless of the chosen management. APM results in a persistent decrease in JSW over at least 72 months. An untreated meniscal tear does not contribute to radiographic progression—assessed by JSW—as compared with an intact meniscus.

Predicted and actual 2-year structural and pain progression in the IMI-APPROACH knee osteoarthritis cohort.

The IMI-APPROACH knee osteoarthritis study used machine learning (ML) to predict structural and/or pain progression, expressed by a structural (S) and pain (P) predicted-progression score, to select patients from existing cohorts. This study evaluates the actual 2-year progression within the IMI-APPROACH, in relation to the predicted-progression scores. Actual structural progression was measured using minimum joint space width (minJSW). Actual pain (progression) was evaluated using the Knee injury and Osteoarthritis Outcomes Score (KOOS) pain questionnaire. Progression was presented as actual change (Δ) after 2 years, and as progression over 2 years based on a per patient fitted regression line using 0, 0.5, 1 and 2-year values. Differences in predicted-progression scores between actual progressors and non-progressors were evaluated. Receiver operating characteristic (ROC) curves were constructed and corresponding area under the curve (AUC) reported. Using Youden's index, optimal cut-offs were chosen to enable evaluation of both predicted-progression scores to identify actual progressors. Actual structural progressors were initially assigned higher S predicted-progression scores compared with structural non-progressors. Likewise, actual pain progressors were assigned higher P predicted-progression scores compared with pain non-progressors. The AUC-ROC for the S predicted-progression score to identify actual structural progressors was poor (0.612 and 0.599 for Δ and regression minJSW, respectively). The AUC-ROC for the P predicted-progression score to identify actual pain progressors were good (0.817 and 0.830 for Δ and regression KOOS pain, respectively). The S and P predicted-progression scores as provided by the ML models developed and used for the selection of IMI-APPROACH patients were to some degree able to distinguish between actual progressors and non-progressors. ClinicalTrials.gov, https://clinicaltrials.gov, NCT03883568.

Quantifying Joint Congruence With an Elastic Foundation.

The level of congruence between the articulating surfaces of a diarthrodial joint can vary substantially between individuals. Quantifying joint congruence using the most widespread metric, the "congruence index," is not straightforward: the areas of the segmented bone that constitute the articular surfaces require accurate identification, their shape must be carefully described with appropriate functions, and the relative orientation of the surfaces measured precisely. In this work, we propose a new method of measuring joint congruence, which does not require these steps. First, a finite element (FE) simulation of an elastic layer compressed between each set of segmented bones is performed. These are then interpreted using the elastic foundation model, enabling an equivalent, but simpler, contact geometry to be identified. From this, the equivalent radius (quantification of joint congruence) is found. This defines the radius of a sphere contacting plane (or "ball on flat") that produces an equivalent contact to that in each joint. The minimal joint space width (in this joint position) can also be estimated from the FE simulations. The new method has been applied to ten healthy instances of the thumb metacarpophalangeal (MCP) joint. The ten thumb MCPs had similar levels and variability of congruence as the other diarthrodial joints that have been characterized previously. This new methodology enables efficient quantification of joint congruence and minimal joint space width directly from CT- or MRI-derived bone geometry in any relative orientation. It lends itself to large data sets and coupling with kinematic models.

OA20 Radiographic hip osteoarthritis classified semi-automatically on dual-energy x-ray absorptiometry scans is strongly predictive of total hip replacement: findings from UK Biobank

Abstract Background/Aims Radiographic hip osteoarthritis (rHOA) is traditionally defined on hip x-rays, using subjective methods such as Kellgren-Lawrence scoring. Associations between subjective rHOA measures and symptoms are inconsistent. Applying digital tools to high-resolution dual-energy X-ray absorptiometry (DXA) scans, we aimed to develop a novel semi-automated classifier for rHOA and evaluate the face validity of the classifier based on relationships with hip pain, hospital diagnosed OA (HES OA), and risk of total hip replacement (THR). Methods Using hip DXAs in UK Biobank, osteophyte grades 0-3 were assigned based on manually measured osteophyte area. Minimum joint space width (mJSW) was automatically measured using outline points placed by a machine learning-based algorithm and then used to categorise individuals into joint space narrowing (JSN) grades 0-3. Osteophyte and JSN grades were combined, using a novel system giving greater to weight to osteophytes, to categorise individuals into rHOA grades 0-4. Logistic regression giving odds ratios (OR) was used to examine associations between rHOA grade and hip pain, and HES OA. Cox proportional hazard models giving hazard ratios (HR) were used to examine associations between rHOA grade and subsequent THR. Our adjusted model included age, sex, height and weight as covariates. Results 40,340 individuals were included in the study (mean age 63.7 [range 44-82], 19294/21046 male/female). 32758 (81.2%) had rHOA grade 0, 4565 (11.3%) grade 1, 2317 (5.7%) grade 2, 543 (1.3%) grade 3, 157 (0.4%) grade 4, with all features of rHOA being more common in males than females. rHOA grades ≥2 were associated with all three clinical outcomes in both unadjusted and adjusted models, a clear dose-response relationship was seen with each increase in grade showing a large rise in OR/HRs (Table 1). Grade 4 rHOA was strongly predictive of THR (HR 57.70 [95%CI 38.08-87.44]). Conclusion We successfully applied a novel semi-automated classifier to over 40,000 individuals from UKB. The validity of our classifier was supported by the strong and progressive relationships observed between rHOA and hip pain, and HES OA and risk of THR. We conclude that hip DXAs provide a promising means of defining rHOA, with potential screening applications in the clinic. Disclosure B.G. Faber: None. R. Ebsim: None. F.R. Saunders: None. M. Frysz: None. C. Lindner: None. J.S. Gregory: None. R.M. Aspden: None. N.C. Harvey: None. G. Davey Smith: None. T. Cootes: None. J.H. Tobias: None.

ASSOCIATIONS BETWEEN PREDICTED AND ACTUAL STRUCTURAL PROGRESSION IN THE APPROACH COHORT

Purpose: Since osteoarthritis (OA) is a heterogeneous disease in terms of progression, many trials include patients showing barely or no progression, particularly in early stages of the disease. In the APPROACH study, machine learning models were trained to predict structural and pain progression of individual participants before inclusion. Predicted progression was differentiated into a structural (S) and pain (P) progression score, where the score (range 0-1) reflected the likelihood of a participant being a progressor. Structural progression was defined as a decrease in minimum joint space width (JSW) of at least 0.3mm/year. Only participants with the estimated highest 75% combined (P+S) score after screening were included. The purpose of the current study was to evaluate the associations between the predicted and actual structural progression according to different parameters over two years.

A GENOME WIDE ASSOCIATION STUDY OF DXA-DERIVED MINIMUM JOINT SPACE WIDTH OF THE HIP PROVIDES FURTHER INSIGHTS INTO ITS GENETIC ARCHITECTURE: FINDINGS FROM UK BIOBANK

Purpose: Cartilage is vital for joint health and function with its degeneration being a key feature of osteoarthritis (OA). Minimum joint space width measured on X-rays (mJSWX-ray) or high-resolution dual-energy X-ray absorptiometry images (mJSWDXA) can provide a proxy for cartilage thickness and pathological joint space narrowing (JSN). Defining the genetic architecture of mJSW provides a route to identify new biological pathways involved in JSN pathogenesis, some of which may represent future therapeutic targets.

Medial Tibial Osteophyte Width Strongly Reflects Medial Meniscus Extrusion Distance and Medial Joint Space Width Moderately Reflects Cartilage Thickness in Knee Radiographs.

BackgroundThe presence of medial tibial osteophytes on knee radiographs suggests cartilage wear, but may be associated with medial meniscus extrusion (MME). The joint space width of the medial compartment consists anatomically of cartilage and the medial meniscus, but which is most responsible for joint space narrowing remains unclear. Magnetic resonance imaging (MRI) reveals MME and cartilage thickness.PurposesTo determine which radiographic medial tibial osteophyte width correlates better with cartilage thickness or MME distance and which radiographic medial joint space width correlates better with cartilage thickness or MME distance.Study TypeCross‐sectional.PopulationTotal of 527 subjects, 253 females and 274 males, aged 30–79 years, included in the Kanagawa Knee Study.Field Strength/Sequence3 T/fat‐suppressed spoiled gradient echo and proton density weighted.AssessmentThe medial tibial osteophyte width and “the minimum joint space width at the medial compartment” (mJSW) were measured from plain radiographs. The cartilage region was automatically extracted from MRI data using software. The medial femoral and tibial cartilage regions were each divided into nine subregions, and the average thickness of the cartilage was determined in each region and subregion. MME was manually measured by two orthopedic surgeons using MRI coronal section images.Statistical TestsPearson's correlation coefficient and their comparison, with P < 0.05 considered statistically significant.ResultsThe absolute values of the correlation coefficients were 0.33 at maximum between osteophyte width and cartilage thickness and 0.76 between osteophyte width and MME; the value was significantly higher with MME than with cartilage thickness (P < 0.001). The absolute values of the correlation coefficients were 0.50 at maximum between mJSW and cartilage thickness and 0.16 between mJSW and MME; the value was significantly higher with cartilage thickness than with MME (P < 0.001).Data ConclusionThe medial tibial osteophyte width strongly reflected MME and the medial joint space width moderately reflected cartilage thickness.Level of Evidence3Technical Efficacy Stage3

Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array.

Osteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers. OA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X-ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients' knee-joint synovial fluid. The WOMAC Index and minimum joint space width before receiving the intra-articular injection and at 2-week intervals were compared. Twelve patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between hypertonic dextrose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. The findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which is accompained by the improvemeny of knee symptoms and associated tendency of upregulation of MMP2, EGF, CXCL 9 and IL-22.

JOINT REPAIR EVALUATED AUTOMATICALLY ON RADIOGRAPHS IS ASSOCIATED WITH PAIN AND SYNOVIAL FLUID MARKER CHANGES AFTER KNEE JOINT DISTRACTION TREATMENT

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. To 1) analyze structural changes after KJD in patients using this AI-based measurement method, and relate these changes to 2) clinical outcome and 3) SF markers. 20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6-7 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ∼one year after treatment. Radiographs were analyzed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria) to obtain whole-joint KL grade, medial and lateral joint space narrowing (JSN) scores, compartmental continuous minimum and standardized JSW, and osteophytes and sclerosis scores of the medial and lateral tibia and femur. 10 Pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analyzed using Wilcoxon Signed Rank tests for categorical and paired t-test for continuous variables. Linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers. After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. Radiographic changes were not statistically significant (p>0.1), except for the medial JSW (p<0.05). A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64; p=0.020). A greater increase in MCP1 (β=0.67; p=0.033) and lower increase in TGFβ1 (β=-0.787; p=0.007) were associated with JSW improvement. Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome. Versus Arthritis project grant (20783), Centre for OA Pathogenesis Versus Arthritis (grants 20205 and 21621), the Kennedy Trust for Rheumatology Research, and ReumaNederland (ISP14-3-301/16-1-404). CS, EB, MD: ImageBiopsyLab GmbH. NA CORRESPONDENCE ADDRESS: m.p.jansen-36@umcutrecht.nl

PREVALENCE OF POTENTIAL MRI-BASED EXCLUSIONARY FINDINGS IN OSTEOARTHRITIS CLINICAL TRIALS: DATA FROM THE OSTEOARTHRITIS INITIATIVE (OAI)

PREVALENCE OF POTENTIAL MRI-BASED EXCLUSIONARY FINDINGS IN OSTEOARTHRITIS CLINICAL TRIALS: DATA FROM THE OSTEOARTHRITIS INITIATIVE (OAI)

PREVALCENCE OF MR‐DECTED CARTILAGE DAMAGE IN KNEES WITH KELLGREN-LAWRENCE 2 & 3 OSTEOARTHRITIS AND IMPLICATIONS FOR CLINICAL TRIALS

Many potential disease-modifying osteoarthritis drugs (DMOADs) have been investigated, but to date no DMOADs that slow or stop disease progression have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A potential reason for the lack of demonstrated efficacy may be reliance on radiographs for defining structural inclusion and exclusion criteria for clinical trials, such as use of joint space width and Kellgren-Lawrence (KL) grade as surrogates for cartilage damage. To estimate the distribution of cartilage damage seen on knee MRI in a sample of knees with radiographic KL 2 and 3 OA that would potentially qualify for a DMOAD trial. We selected knees from the Osteoarthritis Initiative (OAI) that met common structural inclusion criteria for DMOAD trial enrollment at OAI baseline: knees with radiographs centrally graded as KL 2 or 3 and medial minimum joint space width (mJSW) ≥ 1.5mm. A musculoskeletal radiologist with 10 years of experience in semi-quantitative MRI assessment scored knee cartilage damage in the medial and lateral tibiofemoral and patellofemoral compartments using WORMS (Whole-Organ Magnetic Resonance Imaging Score). Coronal intermediate weighted (IW) TSE and sagittal fat-suppressed IW TSE sequences on 3T MRI were used. The WORMS cartilage scores, which are based on both the extent and depth of cartilage damage, were collapsed into 4 categories: no cartilage damage (WORMS 0 and 1), focal partial or full-thickness (PT/FT) cartilage damage (WORMS 2 and 2.5), diffuse partial thickness (PT) cartilage damage (WORMS 3 and 4), and diffuse full-thickness (FT) cartilage damage (WORMS 5 and 6). We estimated the prevalence of each category of cartilage damage in KL2 and KL3 knees; 95% confidence intervals (CI) accounted for clustering at the participant-level since some participants contributed two knees to the analysis. We identified 2,372 participants contributing 3,446 knees with radiographic OA (KL 2 and 3) and medial mJSW ≥ 1.5mm. There were 2,318 KL2 knees and 1,128 KL3 knees. We found no cartilage damage in any compartments in 9.8% (95%CI: 8.5, 11.1) of KL2 knees and 2.0% (95%CI: 1.1, 2.9) of KL3 knees. Cartilage damage was absent in the medial tibiofemoral compartment in 52.4% (95%CI: 50.1, 54.6) of KL2 knees, and 14.4% (95%CI: 12.2, 16.6) of KL3 knees, versus 61% (95%CI: 58.8, 63.2) of KL2 knees and 53.6% (95%CI: 50.4, 56.7) of KL3 knees in the lateral compartment. When medial and lateral compartments were combined, cartilage damage was absent in 34.8% (95%CI: 32.7, 36.9) of the KL2 knees, and 4.3% (95%CI: 3.0, 5.5) of the KL3 knees. Diffuse FT cartilage lesions in the medial compartment were found in 6.1% (95%CI: 5.0, 7.1) of KL2 knees and 42.5% (95%CI: 39.4, 45.6) of KL3 knees. MRI screening prior to clinical trial enrollment may identify a substantial percentage of knees with normal cartilage, as well as knees with diffuse FT cartilage lesions that may not be responsive to DMOADs, depending on the mode of action of a given pharmacological compound. AG has received consultancies fees from Pfizer, Novartis, AstraZeneca, Merck Serono, Regeneron and TissueGene and is shareholder of Boston Imaging Core Lab (BICL), LLC a company providing image assessment services. FWR is shareholder of BICL, LLC and has received consultancies fees from Calibr–California Institute of Biomedical Research and Grünenthal, GmbH. DH receives publication royalties from Wolters-Kluwer. CKK has received consultancy fees from Thuasne, Regeneron, Novartis, Kolon Tissue Gene, Taiwan Liposome, Amzell AZ, LG Chem, Express Scripts, and has received grants from Lilly, Pfizer GSK, Cumberland CORRESPONDENCE ADDRESS: mjarraya@mgh.harvard.edu .

A novel semi-automated classifier of hip osteoarthritis on DXA images shows expected relationships with clinical outcomes in UK Biobank.

Conventional scoring methods for radiographic hip OA (rHOA) are subjective and show inconsistent relationships with clinical outcomes. To provide a more objective rHOA scoring method, we aimed to develop a semi-automated classifier based on DXA images and confirm its relationships with clinical outcomes. Hip DXAs in UK Biobank (UKB) were marked up for osteophyte area from which acetabular, superior and inferior femoral head osteophyte grades were derived. Joint space narrowing (JSN) grade was obtained automatically from minimum joint space width (mJSW) measures. Clinical outcomes related to rHOA comprised hip pain, hospital diagnosed OA (HES OA) and total hip replacement. Logistic regression and Cox proportional hazard modelling were used to examine associations between overall rHOA grade (0-4; derived from combining osteophyte and JSN grades) and the clinical outcomes. A toal of 40 340 individuals were included in the study (mean age 63.7), of whom 81.2% had no evidence of rHOA, while 18.8% had grade ≥1 rHOA. Grade ≥1 osteophytes at each location and JSN were associated with hip pain, HES OA and total hip replacement. Associations with all three clinical outcomes increased progressively according to rHOA grade, with grade 4 rHOA and total hip replacement showing the strongest association [57.70 (38.08-87.44)]. Our novel semi-automated tool provides a useful means for classifying rHOA on hip DXAs, given its strong and progressive relationships with clinical outcomes. These findings suggest DXA scanning can be used to classify rHOA in large DXA-based cohort studies supporting further research, with the future potential for population-based screening.

Three-dimensional analysis for quantification of knee joint space width with weight-bearing CT: comparison with non-weight-bearing CT and weight-bearing radiography

To compare computer-based 3D-analysis for quantification of the femorotibial joint space width (JSW) using weight-bearing cone beam CT (WB-CT), non-weight-bearing multi-detector CT (NWB-CT), and weight-bearing conventional radiographs (WB-XR). Twenty-six participants prospectively underwent NWB-CT, WB-CT, and WB-XR of the knee. For WB-CT and NWB-CT, the average and minimal JSW was quantified by 3D-analysis of the minimal distance of any point of the subchondral tibial bone surface and the femur. Associations with mechanical leg axes and osteoarthritis were evaluated. Minimal JSW of WB-CT was further compared to WB-XR. Two-tailed p-values of <0.05 were considered significant. Significant differences existed of the average medial and lateral JSW between WB-CT and NWB-CT (medial: 4.7 vs 5.1mm [P=0.028], lateral: 6.3 vs 6.8mm [P=0.008]). The minimal JSW on WB-XR (medial:3.1mm, lateral:5.8mm) were significantly wider compared to WB-CT and NWB-CT (both medial:1.8mm, lateral:2.9mm, all p<0.001), but not significantly different between WB-CT and NWB-CT (all p≥0.869). Significant differences between WB-CT and NWB-CT existed in participants with varus knee alignment for the average and the minimal medial JSW (p=0.004 and p=0.011) and for participants with valgus alignment for the average lateral JSW (p=0.013). On WB-CT, 25% of the femorotibial compartments showed bone-on-bone apposition, which was significantly higher when compared to NWB-CT (10%,P=0.008) and WB-XR (8%,P=0.012). Combining WB-CT with 3D-based assessment allows detailed quantification of the femorotibial joint space and the effect of knee alignment on JSW. WB-CT demonstrates significantly more bone-on-bone appositions, which are underestimated or even undetectable on NWB-CT and WB-XR.

Osteophyte size and location on hip DXA scans are associated with hip pain: Findings from a cross sectional study in UK Biobank.

ObjectiveIt remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method.MethodsHip DXAs were obtained from UK Biobank. A novel automated method obtained minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to define rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires.Results6807 hip DXAs were examined. rHOA was present in 353 (5.2%) individuals and was associated with hip pain [OR 2.42 (1.78–3.29)] and hospital diagnosed OA [6.01 (2.98–12.16)]. Total osteophyte area but not mJSW was associated with hip pain in mutually adjusted models [1.31 (1.23–1.39), 0.95 (0.87–1.04) respectively]. On the other hand, JSN as a categorical variable showed weak associations between grade ≥ 1 and grade ≥ 2 JSN with hip pain [1.30 (1.06–1.60), 1.80 (1.34–2.42) respectively]. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain [1.13 (1.06–1.20), 1.13 (1.05–1.24), 1.10 (1.03–1.17) respectively].ConclusionIn this cohort, the relationship between rHOA and prevalent hip pain was explained by 2-dimensional osteophyte area, but not by the apparent mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.