Type X collagen in rabbit and human meniscus.
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Biomedical subjects
Publications and source records attributed to T Conrozier.
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APOPTOSIS IN JOINT CARTILAGE: Apoptosis is the physiologically programmed death of cells to be distinguished from necrosis which caused non-programmed cell death. In joint cartilage, more than 50% of the chondrocytes show signs of apoptosis compared with 10% in normal cartilage. ROLE OF NITRIC OXIDE: In osteoarthritis the production of nitric oxide (NO) appears to be increased, inducing apoptosis of articular chondrocytes stimulated by interleukin 1. NO inhibitors can limit the progression of experimentally induced joint lesions in animal models. IN VITRO RESULTS: The protective effect of the chondroitin sulfates CS4 and CS6 against death of chondrocytes exposed to NO has been demonstrated in vitro. Chondrocytes for New Zealand white rabbits were cultivated in the presence of an NO donor for exposure durations from 12 to 72 hours, with or without adding CS 4&6 to the culture medium. After 3 days of culture, NO induced a significant rise in the number of apoptotic chondrocytes. In 70% of the cases, preventive treatment with 100 micrograms/ml CS 4&6 lowered the number of dead cells. This cytoprotective effect reached a mean 28% and was inversely dependent on the duration of exposure to the NO donor.
CHONDROPROTECTIVE DRUGS: Long-acting chondroprotective drugs have a symptomatic effect. They are only effective in subjects with osteoarthritis and have no pure pain relieving effect. They act within several weeks, improve functional manifestations and have a remnant effect. CHONDROITIN SULFATES 4&6: CS 4&6 are glycosaminoglycans which participate in the matrix structure of cartilage. They are well absorbed after oral intake. They have a dose-dependent inhibitor effect in vitro on proteoglycan and collagen catabolism and have been shown to stimulate matrix synthesis. Several clinical studies have demonstrated the chondroprotective efficacy of CS 4&6 in osteoarthritis involving the hip, knee and finger joints. OSTEOARTHRITIS OF THE KNEE: A controlled randomized double-blind study versus placebo was conducted in 104 patients with femorotibial osteoarthritis. The objective was to demonstrate that CS 4&6 given orally in a sequential regimen at the dose of 800 mg/d has a beneficial effect both in terms of clinical manifestations and in terms of the anatomic progression in patients with osteoarthritis of the knee. The main efficacy criteria was the Lequesne functional score. After 1 year of treatment with CS 4&6, the functional impairment was reduced by approximately 50%, a significant improvement over placebo for all clinical criteria. Tolerance was excellent or good in more than 90% of the cases. A STRUCTURE MODULATOR: This study suggests that chondroitin sulfates act as structure modulators as shown by the improvement in the interarticular space visualized on the x-rays of patients treated with CS 4&6.
UNLABELLED: PROVEN CLINICAL BENEFIT: It has been demonstrated that CS 4&6 administered at the dose of 1200 mg/d for several months is more effective than placebo and as effective as nonsteroidal anti-inflammatory drugs (NSAID) in providing pain relief and improving joint function without risk in subjects with osteoarthritis of the hip and the knee. The beneficial effect persists several weeks after the end of treatment. These advantages should thus have an overall cost-lowering effect. EVALUATION OF THE ECONOMIC IMPACT: A medico-economical study was conducted to reevaluate the beneficial effect of CS 4&6 on the quantity of NSAID prescriptions in France and to determine whether the drug was used correctly in accordance with indications at an adequate dose and treatment duration. DATABASES USED: Two databases, IMS a data bank on medical prescriptions in France, and THALES which gives information on prescriptions by 300 general practitioners, allowed a dynamic analysis of the medical files of 11,000 patients with osteoarthritis. ECONOMICAL BENEFIT: The cost of NSAID prescriptions by general practitioners was reduced by an estimated 67% in patients treated with CS 4&6. In terms of the quantity of NSAID used, the reduction in the CS 4&6 treated group was 63% and 85.3% respectively in patients treated by generalists and by specialists. The quantity of NSAIDs prescribed was reduced by two-thirds when CS 4&6 were represcribed. The cost related to CS 4&6 treatment was compensated for by the reduction in physiotherapy costs and by fewer co-prescriptions for gastroprotective drugs. This study confirmed the randomized clinical studies demonstrating that a regimen of CS 4&6 for several weeks at the dose of 1200 mg/d lowers prescriptions of NSAID which can be completely avoided in nearly half the cases.
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OBJECTIVE: Quantitative evaluation of radiographic methods proposed to improve the detection of joint space narrowing (JSN) in femorotibial osteoarthritis (OA). METHODS: Thirty-two consecutive patients with knee OA and five normal controls had three different weight-bearing radiographs of the knee: (1) anteroposterior film of both knees in full extension (extended knees), (2) anteroposterior film of one knee in extension while the patient was standing on the homolateral foot (standing on homolateral foot), (3) posteroanterior film of both knees flexed at 30 degrees (schuss view). Joint space was analyzed blind using both an evaluation of JSN with a six-grade scale (JSN score) and an image analyser computer measurement of the mean joint space width (mean JSW). The medial compartment of medial femorotibial OA knees, the lateral compartment of lateral femorotibial OA knees, as well as both compartments of control knees, were measured. Extended knee and schuss views were made 1 year later in 10 patients for the evaluation of sensitivity to change. RESULTS: The JSN scores +/- S.D. in schuss, standing on the homolateral foot and extended knee views were 2.75 +/- 1.31, 1.95 +/- 1.3 and 1.66 +/- 1.27, respectively. The mean JSW +/- S.D. in schuss, standing on the homolateral foot, and extended knee views were 2.9 +/- 1.9 mm, 3.5 +/- 1.6 mm and 3.8 +/- 1.5 mm, respectively. Changes in JSN scores and mean JSW with schuss view increased with OA severity. In controls, JSW of the medial compartment did not vary in the three views. JSW of the lateral compartment of controls was significantly larger in the schuss view. The change in JSW after 1 year was -0.41 mm (P = 0.02) in the schuss view and -0.17 mm (P > 0.05) in the extended knee view. CONCLUSION: The schuss view is suggested as the most accurate method for the evaluation of JSW in femorotibial OA.
OBJECTIVES: To evaluate the rate of progression of radiological joint space narrowing (JSN) in patients operated on for hip osteoarthritis (OA) and to determine its predictive factors. METHODS STUDY DESIGN: retrospective longitudinal trial of 61 patients who underwent total hip arthroplasty (THA) for hip OA (69 operated hips). Mean follow-up 81.2 +/- 9.9 months. Collected data: (1) standing frontal radiographs of the pelvis from diagnosis to surgery (246 films) for morphological evaluation and quantitative measurement of joint space width (JSW) (computerized reading of digitized X-rays); (2) demographic data (sex, age, body mass index, smoking status, professional and sporting activities, family history of OA); (3) clinical data (age at onset-diagnosis and THA, drug consumption, time from diagnosis to permanent disability, OA at other joints, previous THA of the contralateral hip). STATISTICS: multivariate analysis. RESULTS: The yearly mean narrowing (YMN) of MeanJSW was 0.43 +/- 0.43 mm/yr (median 0.29, range 0.03-2.55). YMN correlated inversely with joint space width at operation and follow-up duration, and was increased in atrophic OA (r = 0.71). The time between diagnosis and THA correlated with JSW at diagnosis, and was inversely correlated with age at onset and YMN. It was longer in patients with hypertrophic OA (r = 0.69). CONCLUSION: Rapid progression of JSN, older age and absence of osteophytes appear to be the main factors leading to THA.
OBJECTIVE: To evaluate serum concentrations of cartilage oligomeic 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.
OBJECTIVE: To compare serum C-reactive protein levels measured using a highly sensitive immunonephelometry method in patients with rapidly destructive versus slowly progressive hip osteoarthritis. METHODS: Ten patients meeting criteria for rapidly destructive hip osteoarthritis were compared to 25 patients with slowly progressive hip osteoarthritis defined as less than 0.20 mm joint space loss over the last year. Serum C-reactive protein was assayed using an immunonephelometry method with a detection threshold of 0.17 mg/L and a coefficient of variation of less than 5%. RESULTS: One patient in each group was excluded because of a C-reactive protein level greater than 15 mg/L. The mean C-reactive protein level in the remaining 33 patients was 3.05 +/- 3.46 mg/L (range, 0.10-14.9 mg/L). Mean C-reactive protein was significantly higher in the rapidly destructive group than in the slowly progressive group (5.61 +/- 4.75 versus 1.94 +/- 1.98 mg/L, P = 0.01), even after adjustment for potential confounding factors. CONCLUSION: Our data suggest that rapidly destructive hip osteoarthritis may be associated with some degree of inflammation reflected by a small but significant increase in serum C-reactive protein levels.
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.
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Osteoarthritis of the hip is a frequent disease affecting 2 to 4% adults. The main symptoms are inguinal pain, hip movement limitation and thigh muscular atrophy. The diagnosis is usually made of on antero-posterior radiograph of the pelvis and Lequesne's lateral view that show joint space narrowing and osteophytosis. There is no correlation between radiographic lesions and clinical symptoms. The mean rate of joint space narrowing progression was shown to be of about 0.30 mm/year but inter-patients variations are very large. The evolution is more sever in older patients and when there is no osteophyte. New imaging techniques are necessary only if diagnosis is impossible on standard radiographs but not for the surgical decision. The treatment of hip osteoarthritis requires analgesic, NSAIDs and symptomatic slow actin drugs for osteoarthritis. Total hip arthroplasty is necessary when medical treatment is non effective on pain and disability.
Radiographic joint space narrowing is the hallmark of progression in osteoarthritis (OA). An accurate measure of progression for OA requires a precise quantitative method. New techniques have been designed to quantitatively assess knee and hip joint space using computer analysis of digitally stored radiographs. The interobserver coefficient of variation of the technique ranges from 1% to 3.3% and is clearly better than that obtained by the use of dividers and rule. A precise standardization of the radiological procedure as well as use of films of good quality are required for a good reproducibility of the method. The computerized measurement of joint space size from standard radiographs is applicable to monitor progression of hip and knee OA, and appears to be of value in the evaluation of disease-modifying therapies for OA.
Primary systemic amyloidosis rarely affects the walls of small and medium-sized vessels. We report a case of primary AL amyloidosis masquerading as giant cell arteritis at the onset of the disease, revealed by the temporal arteritis biopsy, and successfully treated by corticotherapy for three years. Histology of temporal arteritis confirms the diagnosis of amyloidosis (characteristic birefringence with Congo red). We discuss in this case the diagnosis of primary amyloidosis revealed by Horton disease, or the coincidental association of these two diseases.