Test-retest precision and longitudinal cartilage thickness loss in the IMI-APPROACH cohort.

OBJECTIVE: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. DESIGN: Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 ± 7.1 years, body mass index (BMI): 28.1 ± 5.3 kg/m2, 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: -211 µm) for the quartile with the highest vs the quartile with the lowest s-scores. RESULTS: The test-retest precision was 69 µm for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 µm (95% CI: [-207, -141] µm, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). CONCLUSION: IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. GOV IDENTIFICATION: NCT03883568.

Novel optical spectral transmission (OST)-guided versus conventionally disease activity-guided treatment: study protocol of a randomized clinical trial on guidance of a treat-to-target strategy for early rheumatoid arthritis.

BACKGROUND: Assessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at 'HandScan remission' (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm). METHODS/DESIGN: The study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered. DISCUSSION: The study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients. TRIAL REGISTRATION: Dutch Trial Register, NTR6388. Registered on 6 April 2017 ( NL50026.041.14 ). Protocol version 3.0, 19-01-2017.

Can optical spectral transmission assess ultrasound-detected synovitis in hand osteoarthritis?

OBJECTIVE: To determine whether optical spectral transmission (OST) can be used to assess synovitis in hand and wrist joints of patients with hand osteoarthritis (OA). DESIGN: Hand and wrist joints of 47 primary hand OA patients with at least one clinically inflamed hand or wrist joint were assessed for synovitis by OST and ultrasound (US). Associations between standardized OST and US synovitis were studied in linear mixed effects models, across all joint types together and individually for wrist, proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints, and were adjusted for OA features that showed associations with US synovitis. Diagnostic performance was determined using receiver operator characteristic (ROC) curves analysis, with US as reference standard. RESULTS: Altogether, 6.7% of joints showed US synovitis. Statistically significant associations between OST scores and US synovitis were found for all joints combined (Δ0.37SD, p<0.001) and PIP joints (Δ0.81SD, p<0.001), but not for DIP (Δ0.14SD, p = 0.484) or wrist joints (Δ0.37SD, p = 0.178). All associations were independent of other OA features, i.e. osteophytes and dorsal vascularity. Analysis of diagnostic performance of OST, revealed an area under the ROC curve (AUC-ROC) of 0.74 for all joints together (p<0.001), 0.69 for PIP joints (p<0.001), 0.54 for DIP joints (p = 0.486), and 0.61 for wrist joints (p = 0.234). CONCLUSIONS: OST scores and US synovitis are statistically significantly associated, independent of osteophytes and dorsal vascularity. At this stage, OST performs fair in the assessment of synovitis in PIP joints of hand OA patients.

Proteomics to predict the response to tumour necrosis factor-α inhibitors in rheumatoid arthritis using a supervised cluster-analysis based protein score.

OBJECTIVE: In rheumatoid arthritis (RA), it is of major importance to identify non-responders to tumour necrosis factor-α inhibitors (TNFi) before starting treatment, to prevent a delay in effective treatment. We developed a protein score for the response to TNFi treatment in RA and investigated its predictive value. METHOD: In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP® technology. A supervised cluster analysis method, partial least squares (PLS), was used to select the best combination of proteins. Using logistic regression, a predictive model containing readily available clinical parameters was developed and the potential of this model with and without the protein score to predict European League Against Rheumatism (EULAR) response was assessed using the area under the receiving operating characteristics curve (AUC-ROC) and the net reclassification index (NRI). RESULTS: For the development step (n = 65 patient), PLS revealed 12 important proteins: CCL3 (macrophage inflammatory protein, MIP1a), CCL17 (thymus and activation-regulated chemokine), CCL19 (MIP3b), CCL22 (macrophage-derived chemokine), interleukin-4 (IL-4), IL-6, IL-7, IL-15, soluble cluster of differentiation 14 (sCD14), sCD74 (macrophage migration inhibitory factor), soluble IL-1 receptor I, and soluble tumour necrosis factor receptor II. The protein score scarcely improved the AUC-ROC (0.72 to 0.77) and the ability to improve classification and reclassification (NRI = 0.05). In validation (n = 185), the model including protein score did not improve the AUC-ROC (0.71 to 0.67) or the reclassification (NRI = -0.11). CONCLUSION: No proteomic predictors were identified that were more suitable than clinical parameters in distinguishing TNFi non-responders from responders before the start of treatment. As the results of previous studies and this study are disparate, we currently have no proteomic predictors for the response to TNFi.

Radiographic evaluation of posttraumatic osteoarthritis of the ankle: the Kellgren-Lawrence scale is reliable and correlates with clinical symptoms.

OBJECTIVE: To assess reliability and construct validity of the Kellgren-Lawrence (K&L) scale in posttraumatic ankle osteoarthritis (OA); additionally evaluate the validity of including tibiotalar tilting in the scale. METHOD: One-hundred and fifty ankle radiographs (75 patients, unilateral malleolar fractures) evaluated at average of 18 years after surgery. American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot (HF) score and pain (visual analog scale) were recorded. Grading of OA according to K&L criteria and identification of OA features was performed on standardized radiographs by four physicians. Minimal joint space width, sclerosis, and talar tilt angle were quantified by digital measurements. A modified K&L scale including talar tilting is presented. Validity of original and modified scale was evaluated and expressed as ability to (1) Identify those with clinical symptoms of ankle OA; and (2) Distinguish between different degrees of fracture severity. RESULTS: Inter- and intra-observer reliability of OA assessment according to K&L were good (ICC 0.61 and 0.75). Original and modified K&L grades significantly increased with decreasing AOFAS ankle-HF scores and greater pain. A talar-tilt angle > 2° compared with ≤ 2° in grade 3 was associated with significantly higher pain levels (VAS pain 4.2 vs 1.4, respectively; mean difference 2.8, 95% CI 0.5-5.1). More severe fracture patterns at time of surgery were more often in patients with the highest K&L grades. CONCLUSIONS: The K&L scale is a valid and reliable radiographic grading system for assessment of ankle OA. Inclusion of the talar tilt angle might allow for better differentiation with respect to clinical outcomes.

Patient characteristics as predictors of clinical outcome of distraction in treatment of severe ankle osteoarthritis.

Osteoarthritis (OA) is a slowly progressive joint disease. Joint distraction can be a treatment of choice in case of severe OA. Prediction of failure will facilitate implementation of joint distraction in clinical practice. Patients with severe ankle OA, who underwent joint distraction were included. Survival analysis was performed over 12 years (n = 25 after 12 years). Regression analyses were used to predict failures and clinical benefit at 2 years after joint distraction (n = 111). Survival analysis showed that 44% of the patients failed, 17% within 2 years and 37% within 5 years after joint distraction (n = 48 after 5 years). Survival analysis in subgroups showed that the percentage failure was only different in women (30% after 2 years) versus men (after 11 years still no 30% failure). In the multivariate analyses female gender was predictive for failure 2 years after joint distraction. Gender and functional disability at baseline predicted more pain. Functional disability and pain at baseline were associated with more functional disability. Joint distraction shows a long-term clinical beneficial outcome. However, failure rate is considerable over the years. Female patients have a higher chance of failure during follow-up. Unfortunately, not all potential predictors could be investigated and other clinically significant predictors were not found.

Influence of variation in semiflexed knee positioning during image acquisition on separate quantitative radiographic parameters of osteoarthritis, measured by Knee Images Digital Analysis.

OBJECTIVE: The clinical application of quantitative measurement of separate radiographic parameters of knee osteoarthritis (OA) might be hampered by a lack of reproducible semiflexed joint positioning during acquisition of radiographs. The influence of systematic variations in knee positioning on measurement of separate quantitative radiographic parameters was studied. METHODS: Five components of knee position during radiographic acquisition (beam height, lower and upper leg extension, internal rotation, and lateral shift) were systematically varied within a clinically relevant range, using three cadaver legs. The influence of these variations on the measurement of the separate quantitative radiographic parameters by Knee Images Digital Analysis (KIDA) was evaluated. Significant changes were validated in vivo. Changes were compared with differences during 2-year follow-up in a radiographic progression cohort of early OA. RESULTS: Systematic variation in upper and lower leg extension induced changes in the measurement of joint space width (JSW). Lower leg extension also influenced osteophyte area and eminence height measurement. Also bone density measurement was influenced by variation in all five position components. Variations were of clinical relevance compared with 2-year differences in knees with radiographic progression, and were confirmed in vivo. CONCLUSIONS: Variations in semiflexed knee positioning, which are considered to occur easily during image acquisition in trials and clinical practice despite standardization, are of significant influence on the quantitative measurement of most separate radiographic parameters of OA using KIDA. The additional value of quantitative measurement might improve significantly by better standardization during radiographic acquisition; with radiography still being the gold standard for structure-modification in OA.

Evaluation of separate quantitative radiographic features adds to the prediction of incident radiographic osteoarthritis in individuals with recent onset of knee pain: 5-year follow-up in the CHECK cohort.

OBJECTIVE: Detailed radiographic evaluation might enable the identification of osteoarthritis (OA) earlier in the disease. This study evaluated whether and which separate quantitative features on knee radiographs of individuals with recent onset knee pain are associated with incidence of radiographic OA and persistence and/or progression of clinical OA during 5-year follow-up. METHOD: From the Cohort Hip & Cohort Knee study participants with knee pain at baseline were evaluated. Radiographic OA development was defined as Kellgren & Lawrence (K&L) grade ≥ II at 5-year follow-up. Clinical OA was defined as persistent knee pain and as progression of Westen Ontario & McMaster Universities Osteoarthritis index (WOMAC) pain and function score during follow-up. At baseline radiographic damage was determined by quantitative measurement of separate features using Knee Images Digital Analysis, and by K&L-grading. RESULTS: Measuring osteophyte area [odds ratio (OR) =7.0] and minimum joint space width (OR=0.7), in addition to demographic and clinical characteristics, improved the prediction of radiographic OA 5 years later [area under curve receiver operating characteristic=0.74 vs 0.64 without radiographic features]. When the predictive score (based on multivariate regression coefficients) was larger than the cut-off for optimal specificity, the chance of incident radiographic OA was 54% instead of the prior probability of 19%. Evaluating separate quantitative features performed slightly better than K&L-grading (AUC=0.70). Radiographic characteristics hardly added to prediction of clinical OA. CONCLUSION: In individuals with onset knee pain, radiographic characteristics added to the prediction of radiographic OA development 5 years later. Quantitative radiographic evaluation in individuals with suspected OA is worthwhile when determining treatment strategies and designing clinical trials.

Radiographic features of knee and hip osteoarthritis represent characteristics of an individual, in addition to severity of osteoarthritis.

OBJECTIVE: To evaluate to what extent radiographic features of knees and hips that are normally related to osteoarthritis (OA) represent characteristics of an individual in addition to OA severity. METHODS: We studied a cohort of individuals (n = 1002) with very early signs of hip and knee OA, from the Cohort Hip and Cohort Knee (CHECK) study. Baseline radiographs were evaluated by digital analyses, using Holy's and Knee Images Digital Analysis (KIDA) software, providing distinct quantitative measures of radiographic OA features. In addition, conventional Kellgren and Lawrence (KL) grading was performed. Digital parameters were evaluated for correlations within participants between contralateral (left vs. right hip and left vs. right knee), ipsilateral (e.g. left hip vs. left knee), and diagonal joints (e.g. left hip vs. right knee). Analyses were performed separately for participants with KL grade 0-I and those with evident radiographic OA (KL grade II-III). Regression analyses determined whether demographic characteristics were related to radiographic features. RESULTS: Correlations between digital parameters and KL grade were moderate, and within each KL grade large variation was found. Within participants strong correlations were found for digital parameters between joints in individuals with KL grade 0-I (R = 0.60-0.89), strongest for contralateral comparison, but no statistically significant correlations were found for participants with KL grade II-III. The demographic characteristics age, gender, height, and weight were, to a limited extent (R(2) = 0.01-0.20) but statistically significant, related to radiographic characteristics. CONCLUSION: Using digital analyses of radiographic OA, strong correlations between joints within participants were found. These correlations diminished when OA became evident. This has implications for monitoring joint damage in (very) early OA with digital analyses.

Feasibility of bone density evaluation using plain digital radiography.

OBJECTIVE: For the radiographic evaluation of subchondral bone changes (sclerosis) in osteoarthritis (OA), bone density (BD) is commonly subjectively assessed. BD evaluation using plain digital radiography might be influenced by acquisition and post-processing (PP) settings. Objective of this study was to evaluate the effects of these settings on the measurement of BD using digital radiographs. METHODS: A bone density standard (BDS) of hydroxyapatite (HA) mimicked a BD range of 1.0-5.75 g/cm(2). Digital radiographs were acquired with variation in acquisition settings, and with clinical and minimal PP. An aluminum step wedge served as an internal reference to express the gray values of the BDS in mm aluminum equivalents (mmAl). The relation (R(2)) between actual BD and BD normalized to the reference wedge was evaluated with linear regression analyses for radiographs with variations in PP and acquisition settings. Precision of BD measurement of the BDS was evaluated for application in clinical practice. RESULTS: The correlation between actual BD and BD normalized to the reference was improved by changing PP from clinical (R(2)=0.96) to minimal (R(2)=0.98). Higher tube voltage [kilovolt (kV)] improved the correlation further. Even for clinical PP, average standard deviation (SD) was 0.97 mmAl, much smaller than the change of 2.51 mmAl clinically observed in early OA, which implies the feasibility of BD measurements on digital radiographs. CONCLUSION: Changing PP and acquisition settings in clinical practice can have profound effect on outcome. If done with care, accurate BD measurement is feasible using plain digital radiography.

A systematic review of the association between radiographic and clinical osteoarthritis of hip and knee.

OBJECTIVE: There is ongoing debate on whether an association between radiographic and clinical osteoarthritis (OA) exists. We hypothesized that the inconsistency in the detection of an association might be caused by different definitions of OA, by different radiographic protocols, and by scoring methods for radiographic damage and symptoms. The goal of this study was to evaluate which methodological criteria are important to detect an association between radiographic and clinical OA of hip and knee. METHODS: A literature search was performed with the keywords 'OA', 'hip', 'knee', 'radiographic', and 'clinical' and results were screened for relevant studies. Quality criteria for study characteristics and methodology were developed. Studies were classified according to these criteria and the presence of an association between radiographic and clinical OA was scored. The importance of methodological quality and patient characteristics on the presence of an association was evaluated. RESULTS: The literature search resulted in 39 studies describing an association between radiographic and clinical OA. The frequency of an association between radiographic and clinical OA outcome measures diminished when less quality criteria were fulfilled. Specifically the criterion for standardized outcome measures appeared important in the detection of an association. The association was not influenced by patient characteristics. Only four studies were identified that fulfilled all quality criteria and in these studies an association was found for the knee joint and an inconsistent association was found for the hip joint. CONCLUSION: Methodological quality criteria are of importance to reveal an association between radiographic and clinical OA.

Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK).

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels, alternative approaches such as analyzing skin and urine are needed to study the role of cartilage AGE levels in OA. METHODS: Paired human skin and cartilage samples were obtained post mortem. Paired skin and urine samples were obtained from the CHECK cohort (early OA patients). Pentosidine levels were measured by high-performance liquid chromatography (HPLC). As marker of cumulative cartilage damage X-rays of both knees and hips were scored. Urinary CTXII (uCTXII) levels were measured, to assess current cartilage breakdown. RESULTS: Cartilage and skin pentosidine correlate well (R=0.473, P=0.05). Skin pentosidine was higher in mild (summed (Kellgren & Lawrence K&L) over four large joints ≥4) compared to no (summed K&L≤3) radiographic OA (P=0.007). Urinary pentosidine was not different between these two groups. Skin pentosidine levels were not related to cartilage breakdown (highest vs lowest tertile of uCTXII). Urinary pentosidine, however, was higher in the highest compared to the lowest uCTXII tertile (P=0.009). Multiple regression analysis showed age to be the only predictor of the summed K&L score and age, creatinine clearance and urinary pentosidine as predictors of uCTXII. CONCLUSION: The higher skin and urinary pentosidine levels in those with mild compared to no radiographic joint damage and low vs high cartilage breakdown respectively suggest that AGEs may contribute to disease susceptibility and/or progression. However, relations are weak and cannot be used as surrogate markers of severity of OA.

Digital scoring of haemophilic arthropathy using radiographs is feasible.

Radiographs are important tools to evaluate structural changes in many joint diseases. In the case of haemophilic arthropathy (HA), the Pettersson score is widely used. The rising of digital radiography enables evaluation of these changes in a more quantitative and detailed manner, potentially improving diagnosis and follow-up. The aim of this study was to evaluate whether digital image analysis in the case of HA is feasible, using a presently available method for radiographic changes in knee osteoarthritis (OA), knee image digital analysis (KIDA). Sixty-two knee radiographs were scored according to Pettersson and with KIDA, each by two independent observers. Inter-observer variation and correlations between the two scoring methods were determined. The inter-observer variation was smaller for KIDA than for Pettersson and for KIDA not significantly different from evaluation of OA joints. Good correlations were found for the two methods where comparison of parameters was appropriate. Importantly, for each of the parameters within one point in the ordinal Pettersson score, a large window still existed in the continuous KIDA grading. Digital analysis of radiographs to quantify joint damage in HA is feasible. The use of continuous variables, as used in a digital method such as KIDA has the advantage that it enables objective and much more sensitive detection of small changes than by use of an ordinal analogue method such as the Pettersson score. Based on the present results, it would be worthwhile to adapt the KIDA method for the specific characteristics of HA and to extend the method to elbow and ankle radiographs.

Knee Images Digital Analysis (KIDA): a novel method to quantify individual radiographic features of knee osteoarthritis in detail.

OBJECTIVE: Radiography is still the golden standard for imaging features of osteoarthritis (OA), such as joint space narrowing, subchondral sclerosis, and osteophyte formation. Objective assessment, however, remains difficult. The goal of the present study was to evaluate a novel digital method to analyse standard knee radiographs. METHODS: Standardized radiographs of 20 healthy and 55 OA knees were taken in general practise according to the semi-flexed method by Buckland-Wright. Joint Space Width (JSW), osteophyte area, subchondral bone density, joint angle, and tibial eminence height were measured as continuous variables using newly developed Knee Images Digital Analysis (KIDA) software on a standard PC. Two observers evaluated the radiographs twice, each on two different occasions. The observers were blinded to the source of the radiographs and to their previous measurements. Statistical analysis to compare measurements within and between observers was performed according to Bland and Altman. Correlations between KIDA data and Kellgren & Lawrence (K&L) grade were calculated and data of healthy knees were compared to those of OA knees. RESULTS: Intra- and inter-observer variations for measurement of JSW, subchondral bone density, osteophytes, tibial eminence, and joint angle were small. Significant correlations were found between KIDA parameters and K&L grade. Furthermore, significant differences were found between healthy and OA knees. CONCLUSION: In addition to JSW measurement, objective evaluation of osteophyte formation and subchondral bone density is possible on standard radiographs. The measured differences between OA and healthy individuals suggest that KIDA allows detection of changes in time, although sensitivity to change has to be demonstrated in long-term follow-up studies.

Inhibition of COX-2 by celecoxib in the canine groove model of osteoarthritis.

OBJECTIVE: In vitro studies showed a beneficial effect of celecoxib on proteoglycan turnover and content of osteoarthritic cartilage. In the present study we evaluated whether these favourable effects of celecoxib could also be demonstrated in vivo. METHODS: In 24 Beagle dogs, osteoarthritis (OA) was induced in one knee according to the groove model. The animals were divided into three groups and received oral placebo or 100 or 200 mg celecoxib daily, starting directly after surgery. After 15 weeks joint tissue from all dogs was analysed. RESULTS: Induction of OA resulted in macroscopic and histological damage of cartilage, changes in cartilage proteoglycan turnover, loss of cartilage matrix proteoglycans and slight synovial inflammation, all characteristic of early OA. Surprisingly, none of the parameters was significantly changed upon celecoxib treatment. Synovial fluid prostaglandin E(2) levels were dose-dependently diminished by celecoxib, demonstrating that the celecoxib had reached the joint in sufficient amounts. Using an in vitro setup, canine cartilage under degenerative conditions was favourably influenced by celecoxib, demonstrating that canine cartilage is sensitive to celecoxib. CONCLUSION: The present study showed a chondroneutral effect of celecoxib on the characteristics of experimentally induced OA in vivo, in contrast to the observed beneficial effect in vitro. It could be that celecoxib had been beneficial to degenerated cartilage in vivo but that these effects were counteracted by increased loading of the affected joint and the associated progression of OA, occurring because of the well-known analgesic effects of celecoxib.

Prolonged clinical benefit from joint distraction in the treatment of ankle osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disabling joint disease affecting more than 10% of the adult population. No validated disease-modifying treatment is available. Joint distraction is a relatively new approach to the treatment of severe ankle OA. Short-term (3 years) clinical benefit has been proven, but long-term effects remain to be evaluated. METHODS: Patients with severe OA of the tibio-talar joint, who had been treated with Ilizarov joint distraction more than 7 years previously, were included. Pre-treatment data were obtained by retrospective analysis using questionnaires and patients' charts. Post-treatment assessments were undertaken using the same questionnaires and by physical examination. Three approaches were used and results were compared: the van Valburg score, the Ankle Osteoarthritis Scale (AOS), and a patient satisfaction questionnaire. Retrospectively and prospectively obtained data were available from eight patients for comparison. RESULTS: Twenty-five out of 27 patients with severe ankle OA treated with Ilizarov joint distraction could be traced. Appropriate retrospective data could not be obtained from three patients. Six out of the 22 patients (27%) were failures. In 16 patients (73%), significant improvement in all clinical parameters was observed using each of the three approaches. Good correlations were found between the results of the three methods of assessment and retrospectively obtained pre-treatment values were very similar to the prospective data. CONCLUSIONS: In 73% of the patients, significant clinical benefit from joint distraction of severe OA ankles was maintained for at least 7 years. There is, however, a need for further research to try and predict which patients will not respond to this unconventional form of major surgical intervention.

Steady progression of osteoarthritic features in the canine groove model.

OBJECTIVE: Recently we described a canine model of osteoarthritis (OA), the groove model with features of OA at 10 weeks after induction, identical to those seen in the canine anterior cruciate ligament transection (ACLT) model. This new model depends on cartilage damage accompanied by transient intensified loading of the affected joint. The present study evaluates this groove model at 20 and 40 weeks after induction, to assess whether the osteoarthritic features progress in time. METHODS: Grooves were made in the femoral condyles of one knee without damaging the subchondral bone. After surgery the dogs were forced to load the experimental joint 3 days per week (4 hours/day) for 20 weeks by fixing the contralateral control limb to the trunk. After 20 weeks and 40 weeks (the last 20 weeks normal loading) joints were analysed for biochemical and histological features of OA. RESULTS: All biochemical cartilage parameters were indicative of OA and all these parameters suggested a slow progression of degeneration over time from 20 to 40 weeks after induction, statistically significant for synthesis and content of proteoglycans as well as Mankin grade. Synovial inflammation, which was mild, diminished slightly in time. CONCLUSION: The degenerative joint damage in the canine groove model is slowly progressive over time in the first year. The cartilage degeneration is induced by a one-time trauma and is not primarily mediated by synovial inflammation, which gives this model unique characteristics compared to presently available models for studying early osteoarthritic features in vivo. In the groove model the effect of treatment of cartilage damage is not counteracted by permanent joint instability or hampered by inflammation. Therefore, the model might be more sensitive to detect effects of therapy, aimed at cartilage protection and repair.

The canine 'groove' model, compared with the ACLT model of osteoarthritis.

OBJECTIVE: The frequently used anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in the dog, makes use of a permanent trigger (joint instability) for inducing degenerative changes. The present study evaluates a canine model of degenerative cartilage damage, mimicking OA, which is induced without making use of permanent joint instability. METHODS: The articular cartilage of the weight-bearing areas of the femoral condyles in one knee of ten beagle dogs was damaged by making grooves, without damaging the subchondral bone. Surgery was followed by 10 weeks intensified loading of the affected joint. Subsequently, joint damage and inflammation were evaluated. The effects were compared with those of the ACLT model. RESULTS: Histological analysis showed chondrocyte clusters around cartilage lesions and moderate loss of proteoglycans in the 'groove' model. Synovial inflammation was mild. Biochemical analysis of cartilage showed changes in matrix proteoglycan turnover, proteoglycan content, and collagen damage, all characteristics of OA. Synovial fluid MMP-1, -3 and -13 activity was enhanced. Changes were found in condyles and plateau, were similar for all animals tested, and were similar to the changes observed in the ACLT model. CONCLUSION: The presently described canine 'groove' model shows characteristics identical to those seen in the ACLT model but differs in a way that the changes are induced without joint instability. The latter is expected to make the 'groove' model more sensitive to treatment.

Ankle images digital analysis (AIDA): digital measurement of joint space width and subchondral sclerosis on standard radiographs.

OBJECTIVE: Reliable evaluation of joint space width and subchondral sclerosis of osteoarthritic joints is difficult. The present study describes a new digital method to analyse standard radiographs of the ankle. DESIGN: Standardized radiographs were taken of the ankle of 12 patients with severe osteoarthritis (OA) under full weight-bearing conditions, before treatment and 1 year after initiation of treatment. Treatment consisted of 3 months distraction of the tibio-talar joint, for which clinical benefit has been shown previously. The width of the joint space was measured on digitized images of the radiographs by means of the newly developed semi-automatic digital technique called AIDA (Ankle Images Digital Analysis) and by means of the most widely used conventional analogue measurements. In addition, AIDA was used to assess subchondral sclerosis by measuring the intensity of the radiograph at fixed positions at the bone-cartilage interface. RESULTS: AIDA appeared to be a reliable method for measuring small changes in joint space width and subchondral sclerosis because the intra- and interobserver variation was small. Mean JSW for two observers was 1.96 and 2.00 mm, with mean differences between two observations of 0.05 and -0.01, respectively. Mean subchondral sclerosis in the tibia was 1.52 and 1.61 with mean differences between two observations of, respectively, 0.00 and 0.03. In addition to conventional measurements, AIDA could demonstrate a decrease in subchondral sclerosis as a result of joint distraction of 71% and 69% after 1 year for talus and tibia, respectively. CONCLUSION: The use of AIDA is preferable to the conventional analogue method for evaluating the severity of ankle OA, because the method provides quantitative data not only for the joint space width but also for subchondral sclerosis.