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.

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.

Using ordered values of subregional cartilage thickness change increases sensitivity in detecting risk factors for osteoarthritis progression.

OBJECTIVE: To examine whether ordered values of (sub)regional femorotibial cartilage thickness change are superior to region-based approaches in detecting risk factors for cartilage loss in osteoarthritis (OA). METHODS: 58 women with knee OA had 3 Tesla MR images acquired at baseline and 24 months. Changes in cartilage thickness (∆ThCtAB) were determined in eight medial femorotibial subregions. An ascending sort of individual ∆ThCtAB measurements was done to create "ordered values". Risk factors for cartilage loss considered were: age, BMI, anatomical knee axis (AAA), minimal (medial) joint space width (mJSW), and percent of medial tibial plateau covered by the meniscus (percent cover). All change metrics were tested for association with the risk factors using Kendall's τ and relative sensitivity of multiple tests of subregions and ordered values were compared with single metrics of change from plate and compartment summaries and the first ordered value. RESULTS: The associations between subregion ∆ThCtAB and AAA (P=0.0002), mJSW (P=0.016), and age (P=0.011) were significant, but only AAA (at α=0.05) and age (at α=0.1) remained significant after adjusting for multiple subregions. In contrast, cMFTC had P-values<0.05 for AAA (P=0.0001), mJSW (P=0.016), and meniscus subluxation (0.04). The first ordered value had significant associations with AAA (P=0.0004), mJSW (P=0.003), meniscus subluxation (P=0.02) and percent cover (P=0.031) all of which were significant at α=0.05 after adjusting for tests on multiple risk factors. CONCLUSION: Ordered values of ∆ThCtAB were more sensitive in detecting risk factors of cartilage loss than subregional ∆ThCtAB. Sensitivity was further enhanced by considering the minimum ordered value as a single test, thus not requiring adjustment for multiple tests. Using ordered values there was a significant association between ∆ThCtAB and baseline AAA, mJSW, meniscus subluxation and meniscus percent cover. This study provides an important step in validating ordered values of cartilage change.

Alignment of the medial tibial plateau affects the rate of joint space narrowing in the osteoarthritic knee.

OBJECTIVE: To determine, in serial fixed-flexion (FF) radiographs of subjects with knee osteoarthritis (KOA), the importance of, and basis for, the effect of alignment of the medial tibial plateau (MTP), as determined by the inter-margin distance (IMD), on joint space narrowing (JSN). METHODS: Baseline and 12-month X-rays of 590 knees with Kellgren and Lawrence grade (KLG) 2/3 OA from the public-release dataset of the Osteoarthritis Initiative (OAI) were assigned to subgroups based upon IMD at baseline (IMD(BL)) and the difference between IMD(BL) and IMD(12 mos). Relationships of JSN to IMD(BL) and to the difference between IMD(BL and) IMD(12 mos) were evaluated. RESULTS: In all 590 knees, mean JSN was 0.13 ± 0.51 mm (P<0.0001) and MTP alignment and replication of IMD(BL) in the 12-month film were, in general, poor. JSN was significantly (P=0.012) more rapid in Subgroup A (IMD≤1.70 mm at both time points) than in Subgroup B (both IMDs>1.70 mm): 0.15 ± 0.43; 0.08 ± 0.47. Within Subgroup B we identified a subset, Subgroup B1, in which, although alignment was poor at both time points, the large IMD(BL) was, by chance, highly reproduced by IMD(12 mos) (difference between the two IMDs=0.01 ± 0.27 mm, NS). JSN in Subgroup B1 was 0.06 ± 0.41 mm and did not differ from that in other knees of Subgroup B (P=0.87). The standardized response mean (SRM) in all 590 knees and Subgroups A, B and B1 was 0.25, 0.34, 0.17 and 0.06, respectively. Independent of IMD(BL), JSN correlated significantly with the difference between the IMDs in the two radiographs (r=0.17, P=0.0001). CONCLUSION: Skewed MTP alignment in serial films and poor replication of IMD(BL) in the follow-up exam affect JSN measurement. The magnitude of change in joint space width (JSW) related to the poor quality of alignment that is common with the FF view jeopardizes accurate evaluation of JSN.

Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and Lyon-Schuss radiography.

OBJECTIVE: Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls. METHODS: A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren-Lawrence grade (KLG)2 and 28 KLG3). Lyon-Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined. RESULTS: At 6 months, qMRI demonstrated a -3.7% "annualised" change in cartilage thickness (SRM -0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was -0.68/-0.13 and at 24 months was -0.62/-0.20. The SRM for cMFTC changes measured with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24 months; -2.2%), respectively. CONCLUSIONS: qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.

Subregional femorotibial cartilage morphology in women--comparison between healthy controls and participants with different grades of radiographic knee osteoarthritis.

OBJECTIVE: To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). DESIGN: 158 women aged > or =40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)< or =28, no symptoms, and were AP KLG0. 61 women had a BMI> or =30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. RESULTS: KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. CONCLUSIONS: The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

Relation of regional articular cartilage morphometry and meniscal position by MRI to joint space width in knee radiographs.

OBJECTIVE: To ascertain the contribution of articular cartilage morphometry and meniscal position on MRI to joint space width (JSW) measured in the Lyon schuss radiograph of the knee. DESIGN: 62 obese women with knee OA and 99 non-obese female controls (mean age 56.6 years) were imaged using 3T MRI and coronal water excitation spoiled gradient echo sequences. Segmentation of femorotibial cartilage morphology and regional morphometric analysis was performed using custom software. Meniscal position was measured quantitatively in sagittal and coronal planes. Minimum space width (mJSW) was measured in the Lyon Schuss knee radiograph; Kellgren and Lawrence grades (KLG) were assigned on standing anteroposterior knee films. The relative contribution of regional cartilage thickness and meniscal position to mJSW was assessed initially in univariate models and subsequently with multivariable modelling. RESULTS: 65% of the variation in mJSW was explained by regional cartilage thickness measures, different KLG and meniscal coverage. Of these measures the medial tibia cartilage thickness measures and central region of the central medial femur (ccMF) play a consistent role in variations in mJSW observed across all KLG. Further ccMF and the addition of percent meniscal coverage to this model explains the remaining differences in mean mJSW found between those subjects with definite joint space narrowing (KLG3) and those without OA. CONCLUSION: The variation in radiographic mJSW is best described by five regional cartilage thickness measures and percent meniscal coverage. The magnitude of each measures contribution differs according to radiographic severity with more variability explained by cartilage thickness of ccMF cartilage thickness and percent meniscal coverage with more severe disease.

OARSI-OMERACT definition of relevant radiological progression in hip/knee osteoarthritis.

BACKGROUND: Joint space width (JSW) evaluated in millimeters on plain X-rays is the currently optimal recognized technique to evaluate osteoarthritis (OA) structural progression. Data obtained can be presented at the group level (e.g., mean+/-standard deviation of the changes). Such presentation makes difficult the interpretation of the clinical relevance of the reported results. Therefore, a presentation at the individual level (e.g., % progressors) seems more attractive but requires to determining a cut-off. Several methodologies have been proposed to define cut-offs in JSW: arbitrary chosen cut-off, cut-off based on the validity to predict a relevant end-point such as the requirement of total articular replacement or cut-off based on the measurement error such as smallest detectable difference (SDD). OBJECTIVES: The objective of this OARSI-OMERACT initiative was to define a cut-off evaluated in millimeters on plain X-rays above which a change in JSW could be considered as relevant in patients with hip and knee OA. METHODS: The first step consisted in a systematic literature research performed using Medline database up to July 2007 to obtain all manuscripts published between 1990 and 2007 reporting a cut-off value in JSW evaluated in millimeters at either the knee or hip level. The second step consisted in a consensus based on the best knowledge of the 11 experts with the support of the available evidence. RESULTS: Among the 506 articles selected by the search, 47 articles reported cut-off of JSW in millimeters. There was a broad heterogeneity in cut-off values, whatever the methodologies or the OA localization considered (e.g., from 0.12 to 0.84 mm and from 0.22 to 0.78 mm for Knee (seven studies) and hip (seven studies), respectively when considering the data obtained based on the reliability). Based on the data extracted in the literature, the expert committee proposed a definition of relevant change in JSW based on plain X-rays, on an absolute change of JSW in millimeters and on the measurement error e.g., calculation of the SDD using the Bland and Altman technique. The results of the analysis of JSW should be expressed in terms of a dichotomous variable (e.g., progressors yes/no): a patient with a change in JSW during the study over such SDD will fulfill the definition of "progressor". Moreover, the pilot study aimed at evaluating the measurement error should be designed to reflect the different characteristics of the primary study in which the analysis of the radiological findings will be based on (patient's characteristics, centers characteristics, readers). CONCLUSION: This initiative based on both an Evidence Based Medicine (Systematic Literature Research) and Expert Opinion approach resulted in a proposal of definition of relevant radiological progression in OA to be used as end-point in clinical trials and also recommendations on the conduct of the reliability study allowing such definition.

Reproducibility and sensitivity to change of a new method of computer measurement of joint space width in hip osteoarthritis. Performance of three radiographic views obtained at a 3-year interval.

BACKGROUND: Measurement of radiographic joint space width (JSW) and of joint space narrowing (JSN) is the currently recommended method for assessment of anatomical severity and structural progression of osteoarthritis (OA), respectively. A standard radiographic view of the pelvis is commonly used for measurement of hip OA but other views are available. OBJECTIVES: To evaluate the inter-intra reader reproducibility and the sensitivity to change of a new automated method of measurement of the hip JSW and to assess which radiographic view [pelvis anteroposterior (AP) view, hip AP view, hip oblique view] provides the greatest accuracy for JSW and JSN measurements. MATERIAL AND METHODS: An AP pelvis radiograph, an AP radiograph centered on the target hip (AP hip) and an oblique view were performed at baseline (M0) and 3 years later (M36) in 50 hip OA patients. Two readers, blinded to each other's results and time sequence, measured twice, at a minimum 15 day interval, the six radiographs of each patient, using a novel version of a previously validated software program whose edge-based algorithm automatically detects the joint space contours. Inter-observer cross-sectional (M0+M36) and longitudinal (M0-M36) reproducibility of JSW measurement was assessed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Sensitivity to change was estimated by the standardized response mean (SRM). An ANOVA was used to analyze differences related to the observer and the view. RESULTS: Intra-observer reproducibility: For JSW measurement, the ICC value, for observers 1 and 2 respectively, were 0.92 and 0.83 for the pelvic view, 0.96 and 0.88 for the hip AP view, and 0.90 and 0.86 for the oblique view. For JSN, ICC was 0.94 and 0.82 for the pelvic view, 0.97 and 0.78 for the hip AP view, and 0.95 and 0.86 for the oblique view. Inter-observer reproducibility: For JSW measurement, ICC was 0.87 for the pelvic view, 0.98 for the hip AP view, and 0.87 for the oblique view. The mean inter-observer difference (SD) was 0.0 (0.31), -0.01 (0.15) and -0.04 (0.4)mm for pelvic, AP and oblique views respectively. For JSN, ICC was 0.91 for the pelvic view, 0.93 for the hip AP view, and 0.90 for the oblique view. Sensitivity to change: SRM values were 0.61 (observer 1) and 0.65 (observer 2) for the pelvic view, 0.68 and 0.75, respectively, for the hip AP view, 0.64 and 0.66, respectively, for the oblique view. JSN did not vary significantly with the observer and the view. In 27% of cases intervention by the observer was necessary to correct the computer's identification of the acetabular edge in the area of interest. CONCLUSION: Computer measurement of the radiographic hip joint space provided good intra- and inter-observer reproducibility and good sensitivity to change. However, it was necessary for the observer to intervene frequently to select the area of interest and adjust detection of the bone edge. The hip AP view performed better than the pelvis and oblique views, but not significantly so.

Progressive increase in body mass index is not associated with a progressive increase in joint space narrowing in obese women with osteoarthritis of the knee.

OBJECTIVE: Given that obesity is a risk factor for osteoarthritis (OA) of the knee, a study was undertaken to determine whether progressively higher body mass index (BMI) among obese women is associated with progressive increases in joint space narrowing (JSN). METHODS: Medial compartment JSN over 12 months in Lyon Schuss radiographs of 60 obese women (BMI 30.0-50.5 kg/m(2)) with radiographic and symptomatic OA was compared with that in 81 non-obese women (BMI <28 kg/m(2)) with normal radiographs and minimal or no symptoms of knee OA. RESULTS: Among the patients with OA, higher BMI tended to be associated with a higher Kellgren and Lawrence (KL) grade of OA severity. JSN in the non-obese controls was negligible, but in the 30 patients with KL grade 2 and KL grade 3 knees, mean (SD) JSN was 0.12 (0.31) mm and 0.32 (0.50) mm, respectively (p<0.005 and p<0.001). No association was seen between baseline BMI and 12-month JSN in patients with OA; indeed, the regression plot suggested a slight inverse relationship between the two. CONCLUSIONS: In obese patients with OA, progressively higher BMI values were not accompanied by a progressively increasing rate of JSN. Joint loading was not evaluated, but it is possible that marked obesity limited the functional capacity of some subjects with OA, protecting their knees from loading. For investigators considering eligibility criteria for a trial of a structure-modifying OA drug, these data suggest that recruitment of patients with a BMI much higher than 30 kg/m(2) will not enrich the sample of subjects who will have more rapid JSN than those with a BMI of only 30 kg/m(2).

Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI.

OBJECTIVE: In a multicentre study to explore the effects of licofelone as a disease-modifying osteoarthritis drug in comparison with naproxen in patients with knee osteoarthritis (OA), using MRI and x-ray examination. METHODS: Patients with knee OA (n = 355) were randomised to receive either licofelone (200 mg twice a day) or naproxen (500 mg twice a day). MRI and x-ray examinations were performed at baseline, 6 months (MRI only), 12 and 24 months. MRI was used to assess quantitatively changes in cartilage volume, and x-ray examinations (Lyon-Schuss) to measure changes in the mean and minimum joint space width (JSW) in the medial compartment. Questionnaires probing symptoms were completed. Data were presented as intention to treat (ITT) and according to protocol (ATP). RESULTS: Cartilage volume loss in the global joint and medial and lateral compartments was significantly less in the licofelone than in the naproxen group for ITT at 12 and 24 months and for ATP at all times except in the medial compartment. Patients with medial meniscal extrusion had a greater loss of cartilage volume. In these patients, licofelone markedly reduced the cartilage loss for both ITT and ATP at 12 and 24 months. Although licofelone showed less reduction in the JSW than naproxen, this did not reach significance. All clinical variables were improved at 24 months (p<0.001) for both groups, with a good safety profile. CONCLUSION: Licofelone and naproxen were equally effective in reducing OA symptoms; however, licofelone significantly reduced cartilage volume loss over time, thus having a protective effect in patients with knee OA. This study proves the superiority of quantitative MRI over x-ray examinations in a multicentre clinical trial.

National survey on the non-pharmacological modalities prescribed by French general practitioners in the treatment of lower limb (knee and hip) osteoarthritis. Adherence to the EULAR recommendations and factors influencing adherence.

BACKGROUND: Guidelines for the treatment of lower limb osteoarthritis (LLOA) include non-pharmacological (NPM) and pharmacological modalities (PM). In France, general practitioners (GPs) are the main prescribers of pharmacological treatment for LLOA but little is known about the non-pharmacological modalities they usually prescribe. OBJECTIVE: To determine how French GPs prescribe non-pharmacological modalities of LLOA treatment in daily practice. METHODS: A four-point questionnaire (systematically, frequently, rarely, never) was built to assess the French GPs' opinion regarding the NPM of LLOA treatment (10 questions). The questionnaire was given between April and June 2005 to 3000 GPs, all over the French regions. The percentage reported in this abstract are those of the systematic and frequent responses. RESULTS: 59.2% of the questionnaires (n=1775) could be retrieved. Weight reduction recommendations (76%), joint sparing (71.7%), physical activity development (61.7%), rehabilitation (57.8%), self-exercise (46%) were the more frequently prescribed NPM. Sticks (36%), insoles (35.6%), bed relief (25.4%) and knee bracing (10.5%) were far less regularly proposed. However weight reduction and physical activity development appeared to be the patients less-well observed NPM. The main means used to improve the efficacy of the diet were the support of a nutritionist (74.5%) and the support of the GPs (70.7%) far beyond the support group and familial intervention (both 36,6%). The large majority of GPs considered that a good physical activity was essential (51.7%) or useful (43.3%) to the success of the weight reduction programme. The main recommended physical activities were walking (84.3%), swimming (74.3%), cycling (47%) and water-gymnastics (40.4%). To improve the success of the physical activity development, analgesics were recommended by 93% of GPs, settling up through rehabilitation by 57.4%, support through GPs appointments by 50%. Lastly, 68.4% of GPs recommended a systematic analgesic consumption, since a non-steroidal anti-infammatory drug (NSAID) prescription was proposed by only 30.5%, and NSAID treatment before or after physical activities by 19% and 9.3% respectively. CONCLUSION: This large survey shows that non-pharmacological modalities are frequently prescribed by French GPs in the treatment of LLOA, in addition to analgesic therapy. However, most GPs consider that some of them are difficult to follow in the long term.

Performance of a non-fluoroscopically assisted substitute for the Lyon schuss knee radiograph: quality and reproducibility of positioning and sensitivity to joint space narrowing in osteoarthritic knees.

OBJECTIVE: This study evaluated the longitudinal performance of a modified Lyon schuss (LS) knee examination in the detection of radiographic joint space narrowing (JSN) in knees with osteoarthritis (OA). The modified LS exam entails two to four iterative acquisitions with empirically adjusted angulation of the X-ray beam to achieve superimposition of the anterior and posterior margins of the medial tibial plateau (MTP), a marker of parallel radioanatomic alignment that the original LS exam achieves with fluoroscopically guided beam angulation. METHODS: Seventy-four obese women with symptomatic knee OA underwent LS and fixed-flexion (FF, caudal 10 degrees beam angulation) X-ray exams at baseline and 1 year later. For 47 subjects, beam angulation for both LS exams was guided by fluoroscopy. For 27 subjects, the modified LS exam was performed at one or both times. Modified and original LS procedures were evaluated relative to concurrent FF radiographs with respect to the inter-margin distance (IMD) at the MTP midpoint (quality and reproducibility of alignment) and sensitivity to JSN. RESULTS: Compared to FF radiographs, modified LS radiographs afforded a smaller mean IMD at baseline (0.89 vs 2.06 mm, P=0.002), more reproducible IMD (mean change=0.49 vs 0.91 mm, P=0.007) and more rapid JSN (mean=0.25 vs 0.02 mm/yr, P=0.005). These differences paralleled those observed between original LS and FF procedures with respect to baseline alignment (0.96 vs 1.94 mm, P<0.001), reproducibility of alignment (0.49 vs 1.00 mm, P<0.001) and sensitivity to JSN (0.16 vs -0.01 mm/yr, P=0.007). CONCLUSION: In clinical centers where the absence of fluoroscopy equipment precludes use of the original LS protocol, a modified procedure employing iterative, empirical adjustment of the beam angle to achieve parallel radioanatomic alignment with the MTP affords a degree of superiority over the FF protocol with respect to quality and reproducibility of positioning and sensitivity to JSN in OA knees similar to that of the original.

Serum concentrations of type II collagen biomarkers (C2C, C1, 2C and CPII) suggest different pathophysiologies in patients with hip osteoarthritis.

BACKGROUND: Cartilage destruction in osteoarthritis (OA) involves excessive degradation and increased synthesis of cartilage matrix macromolecules including type II collagen and proteoglycans. Cartilage biomarkers exist for the measurement of cartilage matrix turnover and may reveal differences in patients with OA. OBJECTIVE: To determine whether there are detectable differences in and relationships between biomarkers of type II collagen (CII) degradation (C2C, C1, 2C) and synthesis (CP II) in patients with only hip OA (OHOA) and those suffering from multiple sites OA (MSOA). PATIENTS AND METHODS: Fifty-six patients classified as MSOA or OHOA. Minimum hip joint space width (Min JSW) measured by computer from standard radiographs. Serum measurement of CII synthesis C-propeptide (CPII) and cleavage of type II (C2C) and types I and II (C1, 2C) collagens. Aggrecan metabolism was assessed by serum CS 846 assay. Step to step logistic regression to determine the effect of the quantitative data on the assignment to each subgroup. RESULTS: Twenty-four subjects were classified with MSOA. Among the 32 OHAO patients, 15 had bilateral hip OA and 17 had unilateral hip OA. The latter were classified with "Isolated hip OA" (IHOA). CPII levels were significantly lower in patients with MSOA than in those with OHOA (99.9+/-50.3ng/mL versus 141.9+/-81.2ng/mL, p=0.04. OR= 0.18 for CPII >120 ng/mL, p<0.005). C2C levels were also lower in MSOA (9.7+/-2.3ng/mL) versus OHOA (11.4+/-3.2ng/mL, p=0.03. OR= 0.26 for C2C >10 ng/mL, p=0.02). There was an inverse correlation between min JSW and C2C only in patients with IHOA (r=0.50, p= 0.02). CONCLUSION: Hip OA, in patients with MSOA, might be related to alteration in CII metabolism which may result in a deficient type II collagen repair process. The significant relationship between C2C and JSW in IHOA suggests that this marker is of value in assessing cartilage degradation patients with involvement of a single joint.

Cyclodextrin polysulphate protects articular cartilage in experimental lapine knee osteoarthritis.

OBJECTIVE: To evaluate the in vivo chondroprotective effect of cyclodextrin polysulphate (CDPS) in a rabbit model of experimental osteoarthritis (OA). DESIGN: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). Forty-eight hours post-surgery, the rabbits were randomised into three treatment groups (n=15 in each group) and a sham-operated control group. The rabbits were either injected subcutaneously with saline, 0.25 mg/kg CDPS or 1 mg/kg CDPS once a week for a period of 12 weeks, and their weight was monitored as a parameter for their general status. The animals were then sacrificed for macroscopic and histological assessment of the knee joints. RESULTS: At the lowest dose, CDPS treatment was unable to induce a significant improvement of cartilage degradation vs the saline control in the experimentally induced knee OA. However, subcutaneous injections of 1 mg/kg CDPS induced a marked inhibition (P<0.05) of osteophyte formation. Additionally, a significant reduction of cartilage degradation revealed an overall chondroprotective effect of CDPS at a concentration of 1 mg/kg. No significant effects on weight gain were noted. CONCLUSIONS: Systemic administration of CDPS is able to protect cartilage in vivo and can therefore be considered as a chondroprotective agent with structure modifying capacities.

Head-to-head comparison of the Lyon Schuss and fixed flexion radiographic techniques. Long-term reproducibility in normal knees and sensitivity to change in osteoarthritic knees.

OBJECTIVE: The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x-ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views. METHODS: At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated. RESULTS: In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and -0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p<0.0001). CONCLUSIONS: LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.

Knee joint ultrasonography of the ACLT rabbit experimental model of osteoarthritis: relevance and effectiveness in detecting meniscal lesions.

OBJECTIVES: To develop a protocol for rabbit knee joint ultrasonography (US); to grade ultrasonographically the meniscal injuries of the anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis (OA); to assess with US the effectiveness of the ACLT; to compare final US with macroscopy for the evaluation of medial and lateral meniscal injuries depending on the age and weight when ACLT is performed. METHODS: Twenty-two skeletally mature and adolescent New Zealand white rabbits were housed during the same period at the Institut Claude-Bourgelat, Lyon, France. Surgical ACLT was performed in the left knee of nine adolescent and five adult rabbits. Final US and macroscopic semi-quantitative grading of the meniscal injuries were compared 5 months after ACLT. RESULTS: A standardised protocol was developed to evaluate the rabbit knee joint. US was performed in both control and ACLT knees. Normal and abnormal meniscal US appearances were described. A semi-quantitative scale to grade US meniscal injuries was created. Macroscopic and US total meniscal scores were significantly positively correlated (P<0.001, r=0.70). US detection of meniscal injuries was 92% sensitive and 87.5% specific compared to macroscopy. Positive and negative predictive values of US were, respectively, 92% and 87.5%. US detection of the ACLT effectiveness was 100% specific and 78.5% sensitive. CONCLUSION: A significant relationship was found between ultrasonographic and macroscopic grading of meniscal injuries. US was both specific and sensitive in detecting meniscal lesions. We propose US as a non-invasive, non-expensive, in vivo imaging technique for preclinical studies in the ACLT rabbit OA model.

Non-invasive in vivo quantification of the medial tibial cartilage thickness progression in an osteoarthritis rabbit model with quantitative 3D high resolution micro-MRI.

OBJECTIVE: To develop a quantitative non-invasive in vivo three-dimensional (3D) high resolution (HR) micro-magnetic resonance imaging (microMRI) protocol to measure the medial tibial cartilage thickness (MT.ThC) in the normal rabbit and in the anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis and quantify the progression of MT.ThC. METHODS: The left knee of 10 control and 40 operated rabbits was imaged in vivo with a 7T microMRI system at 3 and 5 months after ACLT. A 3D fast low angle short (FLASH) fat-suppressed MRI protocol was implemented leading to 44x176 microm(3) spatial resolution and to 44 microm(3) isotropic voxel after cubic interpolation. Semi-automatic MT.ThC measurements were made in 3D, in four different locations, in vivo and longitudinally in both groups. At 5 months, gross macroscopy, visual analogical evaluation of the cartilage and histology were compared to the MR-based MT.ThC. RESULTS: At 3 and 5 months, the MT.ThC measured in the minimum interbone distance area was the thinnest MR-based MT.ThC. It was significantly lower in the operated group and among the four evaluated MT.ThC, it was the most discriminative between the normal and the operated groups (P<0.05). The MT.ThC measured in the minimum interbone distance area was also the most sensitive to change in the operated group (66.4% MT.ThC loss, P=0.003) while no significant changes were observed in the control group. CONCLUSION: Quantitative 3D HR microMRI allowed for non-invasive longitudinal MT.ThC measurements in four different locations in both the normal and the operated rabbits. We concluded the MT.ThC measured in the minimum interbone distance area reflected the severity of the disease and was the most effective to measure the progression of the medial tibial cartilage destruction.

Superiority of the Lyon schuss view over the standing anteroposterior view for detecting joint space narrowing, especially in the lateral tibiofemoral compartment, in early knee osteoarthritis.

OBJECTIVE: To evaluate the validity of using the conventional anteroposterior (AP) radiograph of the knee in order to identify joint space narrowing (JSN) at an early stage of osteoarthritis (OA). METHODS: Grading of JSN using a 0-5 score and quantitative measurement of joint space width (JSW) of the medial and lateral compartments of the tibiofemoral joint in AP and fluoroscopically assisted posteroanterior Lyon schuss (LS) radiographs of 202 patients with knee OA. RESULTS: Knees without definite JSN (score <2) were twice as common in AP than in LS radiographs (36.1% vs 18.8%). The number of knees showing definite medial JSN was identical in both views but four knees showing a medial OA in AP view were classified differently in the LS radiographs (three bicompartmental OA and one lateral OA). The frequency of lateral JSN was approximately twice as great in the LS view as in the AP view. JSN score was significantly higher (p<0.001) and JSW was significantly smaller (p<0.01) in the LS view than in the AP view. In knees with definite JSN, JSW of the compartment with no narrowing was significantly (p<0.04) larger than in knees that did not exhibit definite JSN. Medial JSW and lateral JSW were inversely correlated (p<0.001). CONCLUSIONS: The standing AP radiograph performed poorly in identifying both the location of JSN in patients with early tibiofemoral OA (especially, lateral OA) and the severity of JSN. The LS radiographs are preferable to standing AP views for the selection of patients for therapeutic trials of structure-modifying OA drugs.

Differences in biomarkers of type II collagen in atrophic and hypertrophic osteoarthritis of the hip: implications for the differing pathobiologies.

BACKGROUND: Cartilage destruction in osteoarthritis (OA) involves the excessive degradation and increased synthesis of cartilage matrix macromolecules including type II collagen (CII) and proteoglycans. The lack of osteophytes (atrophic form of OA) has been shown to be a disease severity factor in hip OA. Since osteophyte formation involves endochondral ossification and a cartilage intermediate, atrophic OA may also exhibit differences in cartilage turnover compared to hypertrophic OA. Cartilage serum biomarkers may offer an opportunity to identify such differences in patients. AIM: To determine whether serum levels of cartilage biomarkers can distinguish between the presence and absence of osteophyte formation in patients with atrophic and hypertrophic hip OA. PATIENTS AND METHODS: Fifty-six patients (mean age/standard deviation (SD): 62/11; mean body mass index (BMI)/SD: 27/11) with symptomatic hip OA (American College of Rheumatology criteria; mean Lequesne index/SD: 8.3/4) were classified as having an atrophic or hypertrophic form of OA, according to the absence or presence, respectively, of any osteophyte on a standard radiograph of the pelvis. Minimum joint space width (minJSW) and angles of dysplasia [centre-edge (CE) and head-neck-shaft (HNS)] were determined by computerized measurements. The following serum markers were used which are commercial kits from Ibex Diagnostics (Montreal, QC): proteoglycan aggrecans turnover: CS 846; CII synthesis: C-propeptide (CPII), cleavage by collagenase of type II (C2C) and type I and II (C1,2C) collagens. STATISTICS: Patients with atrophic and hypertrophic OA were compared for each variable and step to step logistic regression was used to determine the effect of variables on the belonging to each group. Correlations were examined using linear regression or Spearman test. RESULTS: CPII serum levels were significantly lower in the atrophic OA patients (77.3 vs 117.4 ng/mL). There were no significant differences between groups for C2C, C1,2C and CS 846 . CPII and C2C concentrations were highly correlated in hypertrophic OA (P=0.002) but not in atrophic OA (P=0.8). CONCLUSION: Atrophic hip OA is characterized by reduced synthetic activity involving type II collagen synthesis. This could account in part for the absence of osteophyte formation. The highly significant correlation between CPII and C2C in hypertrophic but not in atrophic OA suggests that the physiological coupling between CII formation and degradation may be lost in atrophic OA. These differences may therefore help explain the absence of osteophyte in atrophic OA and its association with more rapid disease progression.