Thierry Conrozier

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.

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.

Serum concentrations of cartilage oligomeric matrix protein and bone sialoprotein in hip osteoarthritis: A one year prospective study

OBJECTIVE To evaluate serum concentations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) as predictors of disease progression in hip osteoarthrtitis (OA). METHODS Forty eight consecutive patients, referred to hospital for symptomatic hip OA, (ACR criteria) were monitored in a one year prospective trial with radiographs and serum samples. The radiographs were graded for joint space narrowing, osteophytes, and sclerosis and the joint space width was measured by a digitised image analyser. Serum COMP and BSP were quantified by immunoassays. RESULTS The COMP concentrations at baseline correlated with the joint space width at entry and with its yearly mean narrowing (r = 0.38, p = 0.002) but not with joint space narrowing grade progression. The concentrations were higher in patients with bilateral hip OA (p = 0.03). The serum BSP concentrations at baseline were unrelated to OA progression but correlated inversely to the osteophyte grade (r = −0.36, p = 0.004) and sclerosis grade ( r = −0.42, p = 0.0004). CONCLUSION Serum COMP seems to be a surrogate marker of OA and may be of interest for the detection of patients at risk of rapidly progressing disease in hip OA. Serum BSP changes seem to reflect alterations in the subchondral bone turnover in hip OA. Measurement of joint space width using a digitised image analyser is a sensitive way of assessing OA progression that facilitates evaluation of tissue markers in relation to anatomical changes in the joint.

Management of nontuberculous infectious discitis. treatments used in 110 patients admitted to 12 teaching hospitals in France.

The optimal management of pyogenic discitis is not agreed on. No randomized clinical trials of short-course or oral antibiotic regimens have been published to date. To shed light on this issue, we reviewed the management of patients admitted for pyogenic discitis to one of 12 networked rheumatology departments. In this cross-sectional observational study, each department included the first ten patients admitted starting in January 1997 for treatment of pyogenic discitis. One hundred ten patients met the inclusion criteria, 67 men and 43 women, with a mean age of 60.6 +/- 13.7 years (range, 17-86 years). Mean time from symptom onset to diagnosis was 39.6 +/- 39.8 days (range, 24 h-240 days). Blood cultures were positive in 47.3% of patients, and the percutaneous discal and vertebral biopsy in 63.6% of cases; these two investigations identified the causative organism in 79 cases (72.8%). Mean duration of the rheumatology department stay was 31.3 +/- 14.1 days (range, 4-78 days). Antibiotics were given intravenously to 103 (93.6%) patients, for a mean of 25.5 +/- 17.6 days (range, 4-124 days); duration of intravenous antibiotic therapy was longer than 4 weeks in 36.5% of patients. Only seven (6.4%) patients received primary oral antibiotics with no parenteral antibiotics. One hundred patients were given oral antibiotics at the same time as and after intravenous antibiotics, for a mean duration of 87.2 +/- 43.6 day (range, 20-278 days); Bracing was used in 98 (89.1%) patients. Although antibiotic selection was rational and in agreement with current recommendations, wide differences were noted across centers regarding intravenous treatment duration, hospital stay duration, and total treatment duration.

Effect of Hyaluronic Acid in Symptomatic Hip Osteoarthritis : A Multicenter, Randomized, Placebo-Controlled Trial

OBJECTIVE To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA). METHODS A multicenter, randomized, parallel-group, placebo-controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment. RESULTS Eighty-five patients were randomized to the HA group (n = 42) or placebo group (n = 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis (mean +/- SD decrease 7.8 +/- 24.9 mm with HA versus 9.1 +/- 27.4 mm with placebo; P = 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P = 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events. CONCLUSION Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA.

Factors predicting patient satisfaction 2 years after total knee arthroplasty for osteoarthritis

OBJECTIVE To identify factors predicting patient satisfaction 2 years after total knee arthroplasty (TKA) for osteoarthritis. METHODS Prospective multicenter study of patients followed up for 2 years after TKA for osteoarthritis. We evaluated pain and function (Lequesne index and WOMAC) at baseline and after 2 years. After 2 years, the patients rated their satisfaction as a percentage, with values greater than 50% defining good satisfaction. Factors associated with good satisfaction were identified by univariate analyses followed by multivariate analysis. RESULTS Of 299 patients, 264 completed the study (26 were lost to follow-up, six died, and three refused the 2-year evaluation), including 237 (89.8%) with satisfaction scores greater than 50%. Highly significant improvements were found after 2 years versus baseline in the Lequesne index (7.9 vs. 14.5, P<0.0001) and WOMAC index (26.3 vs. 51.3, P<0.0001). There were 26 (9.8%) complications. Factors significantly associated with good satisfaction in the multivariate model were absence of complications (P=0.004), body mass index less than 27 kg/m² (P=0.015), high radiological joint narrowing score (P=0.038), age greater or equal to 70 years (P=0.038), and absence of depression at the 2-year evaluation (P=0.002). CONCLUSION We report the first prospective multicenter study done in France to assess pain and function in a large number of patients treated with TKA for osteoarthritis. Our results indicate a high success rate. We identified three factors that predict patient satisfaction and can be assessed before surgery (age greater than 70 years, absence of obesity, and severe joint space narrowing).

Factors predicting long-term efficacy of Hylan GF-20 viscosupplementation in knee osteoarthritis.

OBJECTIVES To describe the long-term effects of Hylan GF-20 viscosupplementation in patients with knee osteoarthritis and to identify factors predicting efficacy. METHODS One hundred and fifty-five patients (80 women and 75 men; mean age, 69 years) with symptomatic knee osteoarthritis each received three intraarticular Hylan GF-20 injections. Effectiveness, safety, and satisfaction were evaluated 7-14 months later based on a physicians examination and a five-item questionnaire. Radiological data (distribution and degree of joint space loss), size of the effusion (none, moderate, large), injection route (anterior, medial to the patella, or lateral to the patellar), and side effects were recorded. Factors predicting effectiveness were looked for by univariate analysis followed by multivariable analysis with adjustments on age, body mass index, gender, and time from treatment to questionnaire administration. RESULTS Satisfaction was good in 78% and 58.9% of the patients according to the physician examination and questionnaire, respectively. Safety was considered excellent or good in 96.2% of the patients. Factors significantly (P < 0.05) associated with a good outcome were a moderate effusion, injection lateral to the patella, joint space loss in a single compartment, and radiological meniscal calcinosis. CONCLUSION The factors predictive of a good response to Hylan GF-20 in this study need to be confirmed, and their impact quantitated, in prospective studies.

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.

The effects of position on the radiographic joint space in osteoarthritis of the hip

The aim of the study was to assess whether radiographic hip joint space thickness was changed by weight-bearing (WB) compared with non weight-bearing (NWB) position, and to evaluate whether radiographs centered on the hip were more sensitive than pelvic X-rays to detect such a change. Anteroposterior radiographs of the pelvis were made in 30 patients with hip osteoarthritis OA (46 OA and 11 normal hips). Osteoarthritic, as well as contralateral normal hips were analyzed. Radiographs centered on OA hip were performed in 28 other patients. X-rays were made in WB and NWB positions using a standardized radiological procedure. Measurements of mean joint space width (MeanJSW) maximum joint space narrowing (MaxJSN) and joint space surface area (JSA), were made using a computerized image analysis system. The joint space width was unaffected by WB in normal joints but decreased with WB in OA joints. The decrease was significant only when considering MaxJSN in patients with a joint space thickness smaller than 2.5mm. The difference between WB and NWB was larger in radiographs centered on the hip than on pelvic X-rays. MeanJSW and JSA were found to be less sensitive than MaxJSN. The decrease of joint space width was inversely correlated with joint space size in WB. These results suggest that WB radiographs of the hip should be used in preference to NWB in studies of hip OA.

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.