Biomedical subjects

E Vignon

Publications and source records attributed to E Vignon.

At least 19 recordsLinked to original sources

PubMed2007

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.

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PubMed2006

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.

Adult↗

PubMed2006

Increased urinary type II collagen helical and C telopeptide levels are independently associated with a rapidly destructive hip osteoarthritis.

OBJECTIVES: Biochemical markers reflecting the degradation of the type II collagen helical (Helix-II) and type II collagen C telopeptides (CTX-II) have been developed. AIM: To investigate the association of rapidly destructive hip osteoarthritis with urinary Helix-II and urinary CTX-II. PATIENTS AND METHODS: 12 patients (mean age 70 years) meeting the criteria for rapidly destructive hip osteoarthritis and 28 patients with slowly progressive hip osteoarthritis (mean age 63 years) defined as <0.20 mm joint space loss/year were included in a case-control study. In each patient, urinary Helix-II and CTX-II were measured at the end of the follow-up period, with retrospective evaluation of x rays. RESULTS: Helix-II levels were 41% (p = 0.002) higher in the 40 patients with hip osteoarthritis than in 75 healthy controls. Increased Helix-II levels were associated with decreased minimum joint space width of the hip (r = -0.57, p = 0.001). Mean urinary Helix-II levels were 71% higher in rapidly destructive than in slowly progressive disease (mean (standard deviation (SD)) ng/mmol Cr: 396 (160) v 232 (118) ng/mmol; p = 0.002). When levels of Helix-II and CTX-II in the highest tertile were both included in a multivariate logistic regression model, high Helix-II level (OR; (95% CI) 5.73 (1.01 to 32.8)) after adjustment for age and body mass index and high CTX-II level (6.67 (1.14 to 39.0)) were, independently of each other, associated with a rapidly destructive disease. CONCLUSION: Increased urinary Helix-II levels are associated with rapidly destructive hip osteoarthritis, independently of urinary CTX-II. Measurement of Helix-II, alone or in combination with CTX-II, could be useful for the clinical investigation of patients with hip osteoarthritis.

Adult↗

PubMed2006

Continuation of treatment with infliximab in ankylosing spondylitis: 2-yr open follow-up.

OBJECTIVE: To evaluate the continuation and safety of treatment with infliximab in ankylosing spondylitis (AS) over a 2-yr period. METHODS: This study was an open, observational, 2-yr extension study of an open-label study of three induction infusions of infliximab in refractory AS. The fourth infusion was performed only in case of relapse. Thereafter, infliximab was to be administered as needed according to the rheumatologist's opinion; however, for some patients, infusions were performed systematically. RESULTS: None of the 50 recruited patients was lost to follow-up. Thirteen patients (26%) interrupted their treatment by infliximab: four for inefficacy, seven for adverse events, of which four were for allergic reactions to the infusion, and two for other reasons. For all of the 46 patients who had had three infusions judged efficacious and well tolerated, a fourth infusion was performed because of a flare of the disease, after a mean interval of 20.3+/-9.9 weeks (range 7.3-57.9). Over the 24 months, the mean interval between infusions was 11.6+/-9.0 weeks. This interval was longer when patients were treated only as needed (mean 14.3+/-12.1 weeks) than systematically (mean 9.8+/-5.7 weeks). Side-effects were similar to those noted in shorter-term studies; seven patients suffered serious adverse events. There were no deaths, no malignancies and no tuberculosis. CONCLUSION: This study confirms the long-term treatment continuation of infliximab in AS, and shows an acceptable safety profile. It appears that for some patients the disease can be controlled with long intervals between infusions; these findings warrant further studies.

Adult↗

PubMed2006

Assessment of the radioanatomic positioning of the osteoarthritic knee in serial radiographs: comparison of three acquisition techniques.

OBJECTIVE: Recent studies using various standardized radiographic acquisition techniques have demonstrated the necessity of reproducible radioanatomic alignment of the knee to assure precise measurements of medial tibiofemoral joint space width (JSW). The objective of the present study was to characterize the longitudinal performance of several acquisition techniques with respect to long-term reproducibility of positioning of the knee, and the impact of changes in positioning on the rate and variability of joint space narrowing (JSN). METHODS: Eighty subjects were randomly selected from each of three cohorts followed in recent studies of the radiographic progression of knee osteoarthritis (OA): the Health ABC study (paired fixed-flexion [FF] radiographs taken at a 36-month interval); the Glucosamine Arthritis Intervention Trial (GAIT) (paired metatarsophalangeal [MTP] radiographs obtained at a 12-month interval), and a randomized clinical trial of doxycycline (fluoroscopically assisted semiflexed anteroposterior (AP) radiographs taken at a 16-month interval). Manual measurements were obtained from each radiograph to represent markers of radioanatomic positioning of the knee (alignment of the medial tibial plateau and X-ray beam, knee rotation, femorotibial angle) and to evaluate minimum JSW (mJSW) in the medial tibiofemoral compartment. The effects on the mean annualized rate of JSN and on the variability of that rate of highly reproduced vs variable positioning of the knee in serial radiographs were evaluated. RESULTS: Parallel or near-parallel alignment was achieved significantly more frequently with the fluoroscopically guided positioning used in the semiflexed AP protocol than with either the non-fluoroscopic FF or MTP protocol (68% vs 14% for both FF and MTP protocols when measured at the midpoint of the medial compartment; 75% vs 26% and 34% for the FF and MTP protocols, respectively, when measured at the site of mJSW; P<0.001 for each). Knee rotation was reproduced more frequently in semiflexed AP radiographs than in FF radiographs (66% vs 45%, P<0.01). In contrast, the FF technique yielded a greater proportion of paired radiographs in which the femorotibial angle was accurately reproduced than the semiflexed AP or MTP protocol (78% vs 59% and 56%, respectively, P<0.01 for each). Notably, only paired radiographs with parallel or near-parallel alignment exhibited a mean rate of JSN (+/-SD) in the OA knee that was more rapid and less variable than that measured in all knees (0.186+/-0.274 mm/year, standardized response to mean [SRM]=0.68 vs 0.128+/-0.291 mm/year, SRM=0.44). CONCLUSION: This study confirms the importance of parallel radioanatomic alignment of the anterior and posterior margins of the medial tibial plateau in detecting JSN in subjects with knee OA. The use of radiographic methods that assure parallel alignment during serial X-ray examinations will permit the design of more efficient studies of biomarkers of OA progression and of structure modification in knee OA.

Doxycycline↗

PubMed2005

Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort.

OBJECTIVE: To determine whether systemic markers of bone, cartilage, and synovium can predict structural progression of osteoarthritis (OA). METHODS: Patients with painful hip OA were treated with diacerein or placebo in a multicentre, prospective, double blind, 3 year follow up trial. The following information was collected at entry: demographics, characteristics of hip OA, and 10 markers: N-propeptides of collagen types I and III, cartilage oligomeric matrix protein, YKL-40, hyaluronan (sHA), matrix metalloproteinases-1 and -3, C reactive protein, C-terminal crosslinking telopeptides of collagen types I and II (uCTX-II). Radiographs were obtained at entry and every year. Structural progression was defined as a joint space decrease > or =0.5 mm or requirement for total hip replacement. Grouped survival analysis was performed with time to structural progression as dependent variable, and clinical data, radiographic findings, treatment groups (diacerein versus placebo), and markers as explanatory measures. RESULTS: In the 333 patients in whom all markers were measured, high functional impairment, a joint space width <2 mm, and lateral migration of the femoral head at baseline increased the risk of progression, but diacerein had a protective effect (relative risk = 0.75; 95% confidence interval (CI) 0.54 to 0.96). In addition, patients in whom uCTX-II and sHA were in the upper tertile had a relative risk of progression of 3.73 (95% CI 2.48 to 5.61) compared with patients with markers in the two lower tertiles. CONCLUSION: In this large cohort, combined measurements of uCTX-II and sHA were a new predictor of the structural progression of hip OA.

Aged↗

PubMed2004

Serum levels of type IIA procollagen amino terminal propeptide (PIIANP) are decreased in patients with knee osteoarthritis and rheumatoid arthritis.

OBJECTIVE: The aim of this study was to develop a specific immunoassay for PIIANP and measure its serum concentration in healthy controls and in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, we investigated circulating forms recognized by antiserum IIA in pools of serum from healthy adults, patients with OA and patients with RA. DESIGN: Using as immunogen and standard the recombinant human Glutathione S-Transferase (GST)-exon 2 fusion protein of type II collagen, we developed a competitive polyclonal antibody-based ELISA. We compare serum PIIANP levels in 43 patients with knee OA (23 women and 20 men; mean age: 62.6+/-9.6 yr), 63 women with RA (mean age: 54+/-16 yr) and 88 healthy controls (67 women, mean age: 53+/-13 yr and 21 men, mean age: 63+/-7 yr). We randomly selected serum in each group for analyze circulating forms. RESULTS: The immunoassay we developed demonstrated adequate intra and inter-assay precision (CV<10%) and dilution recovery (mean: 96%), allowing accurate measurements of serum PIIANP from 1.13 to 40 ng/ml. No significant cross-reactivity of the ELISA was observed with purified intact human procollagen type I N-propeptide, circulating thrombospondin and von Willebrand factor, proteins which exhibit significant sequence homology with PIIANP. Western blot analysis showed that antiserum IIA recognized two circulating immunoreactive forms of approximately 80 and 100 KDa respectively in serum from healthy adults, patients with OA and RA but also in a pool of synovial fluids from patients with OA. Serum PIIANP levels were markedly decreased in patients with knee OA (12.0+/-3.2 vs 25.8+/-7.5 ng/ml for OA and controls respectively, P<0.0001) and RA (14.1+/-2.5 ng/ml vs 21.7+/-7.6 ng/ml for RA and controls respectively, P<0.0001). In patients with RA, serum PIIANP levels were higher in those taking low-dose prednisone compared to non-users (15.0+/-2.4 vs 13.5+/-2.4 ng/ml, P<0.05). CONCLUSIONS: We have developed the first specific immunoassay for serum PIIANP which exhibits adequate technical performances. This assay detects specifically two immunoreactive forms both in healthy adults and patients with arthritis and does not cross react with other proteins with sequence homology with PIIANP. Levels of PIIANP were significantly decreased in patients with knee OA and RA suggesting that type IIA collagen synthesis may be altered in these arthritic diseases. The measurement of type IIA collagen synthesis with this new molecular marker may be useful for the clinical investigation of patients with joint diseases.

Adult↗

PubMed2004

Measurement of structural progression in osteoarthritis of the hip: the Barcelona consensus group.

OBJECTIVE: To outline the best available method of measurement for detecting progression of osteoarthritis (OA) of the hip especially in therapeutic trials. METHOD: A Medline search of articles related to progression of hip OA was performed. A group of experts met over a 1.5-day session to review available literature and new research. Specific questions were addressed in order to reach a consensus on measuring progression of OA of the hip. RESULTS: Of the available surrogate measures, a single yearly standing or reclined antero-posterior plain radiograph of the pelvis with feet internally rotated 15-20 degrees, can be evaluated with the use of an atlas for joint space width (JSW, interbone distance). There should be a minimum JSW upon baseline screening that may be 1 or 2 mm. Digitization of films offers a slight reduction in variability of measurements. Progression of OA can be calculated by measurement of the JSW on paired and blinded films. A reduction of > or = 0.5 mm is greater than the 'minimum perceptible difference' as well as the variation of most imaging techniques, and represents a clinically relevant and significant reduction in the JSW. Narrowing of the superomedial or superolateral JSW may tend to progress more rapidly than other changes. In clinical trials, patients who discontinue the study treatment need to be followed after discontinuation, and an imputation strategy which provides unbiased estimates of both the treatment effect and its variance is an appropriate technique for intent-to-treat analysis. CONCLUSION: For the development of new agents intended to prevent, retard, stabilize or reverse the progress of OA of the hip, the radiographic methodology presently available is adequate to detect changes in hip JSW of OA.

Arthroscopy↗

PubMed2004

Influence of the quality of tibial plateau alignment on the reproducibility of computer joint space measurement from Lyon schuss radiographic views of the knee in patients with knee osteoarthritis.

RATIONALE: The quality of medial tibial plateau (MT-Plateau) alignment is one of the key elements for accuracy and sensitivity to change of knee radiography in knee osteoarthritis (OA). AIM: To evaluate the influence of the quality of the MT-Plateau alignment on the reproducibility of joint space width (JSW) measurement in knee radiographs. METHODS: One hundred and twenty-seven knee radiographs (99 OA), performed using a standardized radiographic procedure (Lyon schuss (LS) view). Evaluation of the quality of MT-Plateau alignment. Computerized measurement of the JSW, twice, 1-month apart, using a semi-automated and an automated method of measurement. Assessment of the reproducibility of repeated measurements: calculation of intra-observer coefficient of correlation, smallest detectable difference (SDD) and coefficient of variation (CV). RESULTS: MT-Plateau alignment was satisfactory in 99 radiographs (77.9%). Reproducibility was excellent in both satisfactory and non-satisfactory radiographs, irrespective of the method of measurement used. The automated measurement was more reproducible than the semi-automated one (CV 1.15% and 3.23%). SDD and CV were better in satisfactory than in non-satisfactory MT-Plateau aligned radiographs. CONCLUSION: These results confirm that computer measurement of the medial tibio-femoral JSW, from LS digitized radiographs, is highly reproducible, irrespective of the quality of the radiograph. However, the quality of the MT-Plateau alignment influences the reproducibility of JSW measurement. The automated measurement was more reproducible than the semi-automated one.

Aged↗

PubMed2003

Sex differences in hip osteoarthritis: results of a longitudinal study in 508 patients.

OBJECTIVE: To evaluate sex differences in the clinical and structural presentation, and natural history of hip OA. METHODS: A multicentre, prospective, longitudinal, five year follow up study of 508 patients (302 women, 206 men, mean age 63 (7) years) with painful hip OA. Data collected were baseline demographics, symptomatic, therapeutic, and structural variables; symptomatic variables and changes in joint space width (JSW) during the first year's follow up; requirement for total hip arthroplasty (THA) between the end of the first and fifth years. STATISTICAL ANALYSIS: evaluation of sex differences (a) at baseline, in the main characteristics of hip OA using multivariate logistic regression; (b) during the first year of follow up, in the radiological progression of the disease; (c) during the five years of follow up, in the requirement for THA using Kaplan-Meier curves and the log rank test, and of the parameters related to THA, using a multivariate Cox analysis. RESULTS: At entry, women presented more frequently than men with polyarticular OA (mean (SD) articular score 306 (162) v 235 (127)), and superomedial migration of the femoral head (40% v 19%), and had more severe symptomatic disease (patient's overall assessment 46 (23) v 40 (26)). The change in JSW did not differ between women and men after one year, but a greater proportion of women had rapid structural progression (OR=2.34, 95% CI 1.1 to 5.2). THA was performed more often in women. Multivariate analysis suggested that the decision to perform surgery was related more closely to the symptomatic and structural severity of the disease than to the sex of the patient. CONCLUSION: Hip OA in women is more frequently part of a polyarticular OA, and displays greater symptomatic and structural severity.

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PubMed2003

Urinary type II collagen C-telopeptide levels are increased in patients with rapidly destructive hip osteoarthritis.

OBJECTIVE: To compare type II collagen degradation using a new urinary specific marker in patients with rapidly destructive and those with slowly progressive hip OA. METHODS: Twelve patients with rapidly destructive and 28 patients with slowly progressive hip OA were included in a prospective, cross sectional case-control study. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTX-II) as a marker of cartilage degradation were measured by an ELISA, and urinary free deoxypyridinoline (free DPD), a marker of bone resorption, was measured by high performance liquid chromatography. One x ray evaluation of the hips and urine samples was made in all patients when the diagnosis of OA was established. RESULTS: Patients with hip OA had higher mean (SD) urinary CTX-II levels than 65 healthy age matched controls (492 (232) v 342 (141), p<0.001), but no significant difference was seen for urinary free DPD (p=0.30). Increased urinary CTX-II, but not urinary free DPD, correlated significantly with decreased minimum joint space width assessed by radiograph of the hip. Mean urinary CTX-II levels were significantly higher in patients with rapidly progressive OA than in the slowly progressive group (612 (218) v 441 (221), p=0.015), whereas no significant difference of urinary free DPD was seen between the two groups (p=0.55). CONCLUSION: Patients with hip OA have increased CTX-II degradation as assessed by a new urinary marker. Increased urinary CTX-II levels are associated with rapidly destructive disease, suggesting that this marker might be useful in identifying patients with hip OA at high risk for rapid progression of joint damage.

Adult↗

PubMed2002

[Results of the ECHODIAH clinical trial on hip arthrosis].

STUDY OBJECTIVE: The principal objective of ECHODIAH study conducted in patients with hip osteoarthritis was to evaluate the chondroprotective effect of potential of diacerein compared with placebo. The study was conducted over a 3-year period using progression of joint space narrowing as the assessment criterion. RESULTS: For aggravation, expressed as joint space narrowing of at least 0.5 mm, there were significantly fewer patients in the diacerein group than in the placebo group; aggravation came significantly later in the diacerhein group. In the population of patients who completed at least 3 months treatment, the sparing effect on joint space narrowing was 32% in the diacerhein group compared with the placebo group. In addition, the mean progression of joint space narrowing was significantly less in patients treated with diacerein; the mean progression decreased from 0.18 mm/year at the end of the first year to 0.13 mm/year at the end of the third year.

Anthraquinones↗

PubMed2002

Efficacy of infliximab in refractory ankylosing spondylitis: results of a six-month open-label study.

OBJECTIVE: To evaluate the efficacy and safety of a loading regimen of the anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in predominantly axial severe ankylosing spondylitis (AS). METHODS: We enrolled in this study 50 patients (76% males, 87% HLA-B27(+), median age 35 yr, median disease duration 13 yr) with active AS [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >or=30/100 and serum C-reactive protein concentration >or=15 mg/l) despite treatment with a non-steroidal anti-inflammatory drug, and without peripheral arthritis, uveitis or active inflammatory bowel disease. Other disease-modifying anti-rheumatic drugs were discontinued >or=3 months before inclusion and were not allowed during the study. Patients received three infusions of infliximab (5 mg/kg) at weeks 0, 2 and 6 and were monitored clinically and biologically until week 24. RESULTS: Forty-eight patients completed the treatment. In intention-to-treat analysis, all parameters were significantly improved at week 2 and generally reached maximal improvement at week 8. The proportion of responders, defined by a reduction of >or=20% in the global assessment of pain (GAP) or by the AS Assessment Study Group (ASAS 20%) criteria, and the proportion of patients reaching partial remission were 98, 94 and 70% respectively. Relapse, defined as >or=50% loss of maximal GAP improvement, occurred in 73% of completers, with a median delay of 14 weeks after the third infusion. No serious adverse event related to the treatment was observed. CONCLUSIONS: This study confirms, in a large group of severely affected AS patients, the remarkable efficacy of infliximab. Relapse usually occurred after discontinuation of the drug, but almost one-third of completers were still free of relapse 4 months after the last infusion.

Adult↗

PubMed2002

Relevant change in radiological progression in patients with hip osteoarthritis. I. Determination using predictive validity for total hip arthroplasty.

OBJECTIVE: To determine a cut-off point above which a change in joint space width (JSW) could be considered as relevant in patients with hip osteoarthritis (OA) on the basis of predicted need for subsequent total hip arthroplasty (THA). METHODS: A multicentre, prospective, longitudinal, 5-yr follow-up study was performed. A pelvic radiograph was obtained at entry and after 1 and 2 yr. For each film, the narrowest JSW was measured using a 0.1 mm graduated magnifying glass. The absolute and relative differences between baseline and 1 and 2 yr of follow-up were calculated. We determined the cut-off points above which an absolute or relative decrease in JSW between baseline and 1 and 2 yr of follow-up could be considered relevant on the basis of the predicted need for THA during the remaining years of the study. The need for THA was categorized as 'yes' or 'no'. Thereafter, for each observed change in JSW (0.1 per 0.1 mm or 1% per 1%), the sensitivity and specificity for subsequent THA were calculated. The choice of cut-off was based on maximal sensitivity and specificity, using the graphic representation of correct classification probabilities. In this way it was possible to obtain the best measured JSW threshold with maximal true positive and minimal false positive results. RESULTS: A total of 423 and 385 patients met the criteria for analysis using the decrease in JSW between baseline and 1 and 2 yr respectively. The best cut-off points were absolute decreases in JSW of 0.2 and 0.4 mm and relative decreases in JSW of 15 and 20% after 1 and 2 yr respectively, with corresponding ranges of sensitivity and specificity of 68-75 and 67-78%. CONCLUSION: This work determined the cut-off above which a change in JSW could be considered clinically relevant in patients with hip OA, on the basis of predicted subsequent need for THA. For validation, similar studies should be conducted in other countries with different health-care systems.

Aged↗

PubMed2002

Relevant change in radiological progression in patients with hip osteoarthritis. II. Determination using an expert opinion approach.

AIM: To determine the minimum clinically important difference (MCID) in joint space width (JSW) progression in patients with hip osteoarthritis (OA), based upon evaluation by a panel of clinical experts as a gold standard. METHODS: A sample of 298 patients with hip OA was selected from a multicentre, prospective, longitudinal, 3-yr follow-up study. A pelvic radiograph was obtained at entry and after 3 yr. For each film, the narrowest JSW was measured using a 0.1-mm graduated magnifying glass. The difference between baseline and 3-yr follow-up JSW was calculated. Two senior rheumatologists, who were experts in osteoarthritis, evaluated each pair of films and noted whether a clinically relevant deterioration in osteoarthritis stage occurred at 3 yr compared with baseline. Interobserver reliabilities were evaluated using the kappa coefficient and proportions of agreements. Then, for each measured difference in JSW (0.1 mm per 0.1 mm), the sensitivity and specificity for MCID, defined as the assessment of expert 1, expert 2 or a combination of both, were calculated. This allowed us to obtain, from graphic representations of the correct classification probabilities, the best measured JSW threshold, with the maximal true positive and the minimal false positive results. RESULTS: The mean measured change in JSW was -0.63 +/- 0.74 mm. Experts 1 and 2 considered the decrease in JSW to be clinically relevant in 122 (40.9%) and 100 pairs (33.6%) respectively. The proportion of agreements between the experts was 79.9%, with a kappa coefficient of 0.572. The best measured JSW threshold was -0.4 mm for expert 1, expert 2 and the combination of both; sensitivity and specificity were 0.75 and 0.8, 0.71 and 0.72, and 0.75 and 0.7 respectively. CONCLUSION: This study suggests that a change of at least 0.4 mm in the radiological JSW could be considered clinically relevant. Other studies using other sets of patients and other methods are needed for validation.

Aged↗

PubMed2002

Differential gene expression analysis in a rabbit model of osteoarthritis induced by anterior cruciate ligament (ACL) section.

Osteoarthritis (OA) is the most common of all joint diseases to affect mankind and is characterized by the degradation of articular cartilage. The low availability of normal and pathologic human cartilage and the inability to study the early stages of the disease in humans has led to the development of numerous animal models of OA. The aim of our study was to establish gene expression profiles during the progression of a rabbit model of OA induced by anterior cruciate ligament (ACL) section. Semiquantitative RT-PCR was used to follow expression of several relevant molecules (type II and X collagens, aggrecan, osteonectin, betaig-h3, BiP, TIMP-1, MMP-1, -3, -13, aggrecanase-1, -2) during development of OA in articular cartilage. In parallel, we monitored the activities of collagenase, caseinase, phospholipase A2 and glycosyltransferases (xylosyl-, galactosyl-, glucuronyl- and N-acetyl-galactosaminyl-transferase). Novel cDNA clones for rabbit type X collagen, aggrecanase-1 and -2, osteonectin and BiP were constructed to obtain species-specific primers. Ours result show that MMP-13 (collagenase-3) gene expression increased dramatically early after ACL surgery and remained high thereafter. An increase in MMP-1 (collagenase-1) and MMP-3 expression was also noted with an absence of variation for TIMP-1 expression. In addition, the global MMPs activities paralleled the MMP gene expression. These data together characterize at the molecular level the evolution of OA in this rabbit model. Furthermore, we have undertaken a search for identifying differentially expressed genes in normal and OA cartilage in this model, by differential display RT-PCR. We present here preliminary results with the determination of the best technical conditions to obtain reproducible electrophoresis patterns of differential display RT-PCR.

Aggrecans↗

PubMed2001

Matrix metalloproteinase-1, -3, -13 and aggrecanase-1 and -2 are differentially expressed in experimental osteoarthritis.

The aim of this study was to characterize the cellular phenotypes of articular cartilage and meniscus in rabbits with experimentally induced osteoarthritis (OA), by histological and molecular biological techniques. OA was induced by severing the anterior cruciate ligament of the knee and rabbits were killed 2, 4 or 9 weeks following surgery. Our histological observations show a progressive destruction of extracellular matrix in both tissues. To determine whether these morphological changes could be related to alterations in the regulation of gene expression for a subset of relevant molecules, levels of mRNA for proteinases and one inhibitor (MMP-1, -3 and -13, aggrecanase-1 and -2 and TIMP-1), matrix molecules and one chaperone (type II and X collagens, aggrecan, osteonectin, betaig-h3 and BiP) were assessed by reverse transcription-polymerase chain reaction. Our results indicate that for most markers expression profiles were similar in both tissues. In particular, matrix protein gene expression remained stable or varied little during progression of OA, suggesting a poor repair capacity of the tissues. MMP gene expression increased rapidly whereas aggrecanase gene expression remained stable. These findings suggest that differential regulation of mRNA levels of MMP-1, -3 and -13 on the one hand and aggrecanase-1 and -2 on the other, occurs during OA.

ADAM Proteins↗

PubMed2001

Formation and phenotype of cell clusters in osteoarthritic meniscus.

OBJECTIVE: To determine the histologic changes that accompany the formation of cell clusters during the early stages of osteoarthritis development in the meniscus, and to characterize the expression phenotype of these cells. METHODS: Histologic sections of medial menisci from normal and anterior cruciate ligament (ACL)-deficient rabbit knees were immunolabeled with monoclonal antibodies for vimentin to highlight the cytoskeleton of meniscal cells, Ki-67 to identify proliferating cells, and type X collagen to evaluate changes in the cell expression phenotype. Tissue mineralization was assessed by specific staining with alizarin red. RESULTS: Following ACL transection, there was an alteration in the normal interconnected network of meniscal cells in the fibrocartilaginous region of the tissue. This led to isolation of islands of cells within the extracellular matrix of the meniscal tissue. These islands of cells displayed 3 different morphologies based on cell composition: 1) stellate cells, 2) stellate as well as round cells, and 3) round cells. Islands composed solely of round cells were more prominent in the latter stages following ACL transection, and the size of these islands increased with time, apparently as the result of cell proliferation. These islands of cells corresponded to the "clusters" previously described in osteoarthritic cartilage. Strong expression of type X collagen colocalized with the deposition of calcium within the meniscal regions enriched with cell clusters. CONCLUSION: Based on the observed changes in cell distribution, morphology, and cell proliferation as well as the previous detection of apoptosis in similar studies of rabbit knee joints, we propose a model for the development of cell clusters in the osteoarthritic meniscus. The morphologic appearance as well as the type X collagen expression phenotype of the meniscal cells forming the clusters is similar to that of hypertrophic chondrocytes. These findings provide a basis for understanding the origin of cell clusters in other joint connective tissues, such as osteoarthritic cartilage.

Animals↗