[Pharmaceutical interviews for rheumatoid arthritis patients: Perceptions and expectations of community pharmacists]. / Entretiens pharmaceutiques destinés aux patients atteints de polyarthrite rhumatoïde : perceptions et attentes des pharmaciens d'officine.

INTRODUCTION: Rheumatoid arthritis has a low level of medication adherence. Abroad, the community pharmacist has a positive impact on the patients' adherence in several chronic diseases. In France, community pharmacists' missions are developing with the implementation of pharmaceutical interviews. OBJECTIVE: To evaluate community pharmacists' perceptions on the interest and feasibility of pharmaceutical interviews targeting patients with rheumatoid arthritis. METHOD: Semi-structured interviews were conducted between August and October 2017, with pharmacists in the Auvergne-Rhône-Alpes region. The inductive analysis of the interview verbatim was realized by two independent persons. RESULTS: Fifteen community pharmacists highlighted barriers in recruiting patients for the interviews currently possible at the pharmacy, the complexity of the organization and the financing, a weakness of the hospital-to-community liaison. Nevertheless pharmacists were motivated to expand the service to other pathologies. Regarding rheumatoid arthritis, pharmacists would see them in the form of structured interviews preferentially at the pharmacy, in connection or even "prescribed" by physicians for optimal and multi-professional information sharing. Prior training and funding for these interviews should be considered to motivate pharmacists to this activity. CONCLUSION: This study allowed to discuss with community pharmacists their expectations and needs to widen the service of pharmaceutical interviews in the rheumatoid arthritis. These results will have to be taken into account to build a support interviews model for rheumatoid arthritis patients who can be integrated in their daily pharmaceutical activity.

Autologous chondrocyte implantation for traumatic full-thickness cartilage defects of the knee in 14 patients: 6-year functional outcomes.

BACKGROUND: Autologous chondrocyte implantation (ACI) was introduced in 1987 in Sweden by Brittberg and Peterson for the treatment of severe chondral defects of the knee. Here, our objective was to evaluate mid-term outcomes of ACI in young athletic patients with deep chondral defects of the knee after trauma. HYPOTHESIS: ACI is effective in filling full-thickness chondral defects of the knee. PATIENTS AND METHODS: We prospectively monitored 14 patients, with International Cartilage Repair Society grade III or IV lesions, who underwent ACI between 2001 and 2006. Standard evaluation measurements were used. Mean age at surgery was 37.7 years (range, 30-45). A history of surgery on the same knee was noted in ten (67%) patients. The defect was on the medial femoral condyle in 11 patients, lateral femoral condyle in two patients, and both femoral condyles in one patient. Mean defect surface area after debridement was 2.1cm(2) (1-6.3). RESULTS: After a mean follow-up of six years, improvements were noted in 12 (86%) patients, with an International Knee Documentation Committee (IKDC) score increase from 40 (27.6-65.5) to 60.2 (35.6-89.6) (P=0.003) and a Brittberg-Perterson score decrease from 54.4 (11.8-98.2) to 32.9 (0-83.9) (P=0.02), between the preoperative assessment and last follow-up. The visual analogic scale pain score decreased from 66.3 (44-89) to 23.2 (0-77) (P=0.0006). In two (14%) patients, no improvements were detectable at last follow-up. The remaining 12 patients were satisfied and able to resume sporting activities, albeit at a less strenuous level. Two ACI-specific complications occurred, namely, periosteal hypertrophy treated with debridement in one patient and transplant delamination in another. DISCUSSION: Our findings are consistent with previous reports but cover a longer follow-up period. Although the outcomes are promising, longer follow-ups are needed to confirm the long-term effectiveness of ACI. LEVEL OF EVIDENCE: IV, prospective therapeutic study.

Chronic exposure of bone morphogenetic protein-2 favors chondrogenic expression in human articular chondrocytes amplified in monolayer cultures.

Articular cartilage is a specialized connective tissue containing chondrocytes embedded in a network of extracellular macromolecules such as type II collagen and presents poor capacity to self-repair. Autologous chondrocyte transplantation (ACT) is worldwide used for treatment of focal damage to articular cartilage. However, dedifferentiation of chondrocytes occurs during the long term culture necessary for mass cell production. The aim of this study was to investigate if addition of bone morphogenetic protein (BMP)-2, a strong inducer of chondrogenic expression, to human chondrocytes immediately after their isolation from cartilage, could help to maintain their chondrogenic phenotype in long-term culture conditions. Human articular chondrocytes were cultured according to the procedure used for ACT. Real-time PCR and Western blotting were performed to evaluate the cellular phenotype. Exogenous BMP-2 dramatically improves the chondrogenic character of knee articular chondrocytes amplified over two passages, as assessed by the BMP-2 stimulation on type II procollagen expression and synthesis. This study reveals that BMP-2 could potentially serve as a therapeutic agent for supporting the chondrogenic phenotype of human articular chondrocytes expanded in the conditions generally used for ACT.

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.

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.

[Human chondrocyte responsiveness to bone morphogenetic protein-2 after their in vitro dedifferentiation: potential use of bone morphogenetic protein-2 for cartilage cell therapy]. / Réponse des chondrocytes humains à la bone morphogenetic protein-2 après leur dédifférenciation in vitro : utilisation potentielle de la bone morphogenetic protein-2 pour la thérapie cellulaire du cartilage.

AIM OF THE STUDY: Cartilage has a limited capacity for healing after trauma. Autologous chondrocyte implantation is widely used for the treatment of patients with focal damage to articular cartilage. Chondrocytes are isolated from biopsy specimen, cultured in monolayers on plastic then transplanted over the cartilage defect. However, chondrocyte amplification on plastic triggers their dedifferentiation. This phenomenon is characterized by loss of expression of type II collagen, the most abundant cartilage protein. The challenge for autologous chondrocyte implantation is to provide patients with well-differentiated cells. The aim of the present study was to test the capability of bone morphogenetic protein (BMP)-2 to promote redifferentiation of human chondrocytes after their expansion on plastic. MATERIALS AND METHODS: Chondrocytes extracted from nasal cartilage obtained after septoplasty were serially cultured in monolayers. After one, two or three passages, BMP-2 was added to the culture medium. The cellular phenotype was characterized at the gene level by using RT-PCR. The expression of genes coding for type II procollagen with the ratio of IIB/IIA forms, aggrecan, Sox9, osteocalcin and type I procollagen was monitored. RESULTS: Our results show that BMP-2 can stimulate chondrogenic expression of the chondrocytes amplified on plastic, without inducing osteogenic expression. However, this stimulatory effect decreases with the number of passages. CONCLUSION: The efficiency of autologous chondrocyte implantation could be improved by using chondrocytes treated with BMP-2 during their in vitro preparation.

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.

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.

Seguimiento de niños con syndrome de Down en el Hospital Materno Intantil “Ramón Sardᔠde Buenos Aires, Argentina / Follow up of the children seen at the “Ramon Sardᔠmaternal hospital of Buenos Aires, Argentina

Se presentan los resultados del programa de seguimiento de niños con síndrome de Down (SD), Grupo A.t.i.e.n.d.o (Atención interdisciplinaria en niños con SD) nacidos en su mayoría en el Hospital Materno-Infantil “Ramón Sardᔠ(HMIRS) de Buenos Aires, Argentina. Se describe el programa, características de la población estudiada, resultados, incidencia de las patologías más frecuentes y modalidades de intervención para favorecer la integración social y familiar (AU)

We show the results of the following program in children with Down Syndrome (DS), seen by the ATIENDO group (Interdisciplinary Attention in children with DS) in the Maternal Hospital Ramón Sardá of Buenos Aires Argentina. We describe the program, the study population, associated illness, the results, and ways to intervention to promote familiar and social integration in these children (AU)

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.

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.

Epidemiological, clinical, biological and radiological differences between atrophic and hypertrophic patterns of hip osteoarthritis: a case-control study.

OBJECTIVE: Lack of osteophytes (atrophic form) has been shown to be a factor in the severity of hip osteoarthritis (OA). The aim of this study was to determine the epidemiological, radiological and biological differences between the hypertrophic and atrophic forms of hip osteoarthritis. METHODS: 25 patients with symptomatic hip OA (ACR criteria) and classified as having an atrophic form of OA based on the lack of osteophytes on standard radiograph of the pelvis, were matched for joint space width with 25 subjects with evidence of the hypertrophic form of hip OA. OA radiological severity was assessed using a scoring system and by computer measurement of the joint space width. Angles of hip dysplasia were measured. Serum hyaluronic acid, cartilage oligomeric matrix protein, collagenase, Type I procollagen, C-terminal crosslinking telopeptide of type I collagen and tissue inhibitor of métalloproteases-1 were assayed by immunoassay and C-reactive protein by ultrasensitive immunonephelemetry. Statistical analysis was performed using logistic regression, taking into account age, sex, body mass index, and bilaterality. RESULTS: Compared to hypertrophic OA, atrophic OA affected chiefly elderly women and was characterized by a smaller centre-edge angle and diffuse superior femoral head migration. It was less frequently bilateral. No statistically significant difference was found in the biological data between the two groups. CONCLUSION: An atrophic bone response in hip OA occurs chiefly in women and is associated with poor coverage of the femoral head. Serum biomarkers able to demonstrate differences between the atrophic and hypertrophic patterns of OA are lacking.

Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage.

OBJECTIVE: To analyse the relations between the urinary levels of type II collagen C-telopeptide (CTX-II) and glucosyl-galactosyl pyridinoline (Glc-Gal-PYD)-two newly developed biochemical markers of type II collagen and synovial tissue destruction respectively-disease activity and the severity of joint destruction in patients with knee osteoarthritis (OA). The clinical performance of these two new markers was compared with that of a panel of other established biochemical markers of connective tissue metabolism. METHODS: The following biochemical markers were measured in a group of 67 patients with knee OA (mean age 64 years, median disease duration eight years ) and in 67 healthy controls: for bone, serum osteocalcin, serum and urinary C-telopeptide of type I collagen (CTX-I); for cartilage, urinary CTX-II, serum cartilage oligomeric matrix protein (COMP), and serum human cartilage glycoprotein 39 (YKL-40); for synovium, urinary Glc-Gal-PYD, serum type III collagen N-propeptide (PIIINP), serum hyaluronic acid (HA); and for inflammation, serum C reactive protein. Biochemical markers were correlated with pain and physical function (WOMAC index) and with quantitative radiographic evaluation of the joint space using the posteroanterior view of the knees flexed at 30 degrees. RESULTS: All bone turnover markers were decreased in patients with knee OA compared with controls (-36%, -38%, and -52%, p<0.0001 for serum osteocalcin, serum CTX-I and urinary CTX-I, respectively). Serum COMP (+16%, p=0.0004), urinary CTX-II (+25%, p=0.0009), urinary Glc-Gal-PYD (+18%, p=0.028), serum PIIINP (+33%, p<0.0001), and serum HA (+ 233%, p<0.0001) were increased. By univariate analyses, increased urinary Glc-Gal-PYD (r=0.41, p=0.002) and decreased serum osteocalcin (r=-0.30, p=0.025) were associated with a higher total WOMAC index. Increased urinary CTX-II (r=-0.40, p=0.0002) and Glc-Gal-PYD (r=-0.30, p=0.0046) and serum PIIINP (r=-0.29, p=0.0034) were the only markers which correlated with joint surface area. By multivariate analyses, urinary Glc-Gal-PYD and CTX-II were the most important predictors of the WOMAC index and joint damage, respectively. CONCLUSION: Knee OA appears to be characterised by a systemic decrease of bone turnover and increased cartilage and synovial tissue turnover. CTX-II, Glc-Gal-PYD, and PIIINP may be useful markers of disease severity in patients with knee OA.

Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro.

OBJECTIVE: The efficacy of glucosamine sulfate (GS) in the symptomatic treatment of patients with osteoarthritis (OA) is suggested to be mediated by still unknown effects on the altered OA cartilage. DESIGN: Using human OA chondrocytes in culture, the effects of GS on protein synthesis, caseinase, collagenase, phospholipase A2 (PLA2) and protein kinase C (PKC) activities as well as production of nitric oxide and cyclic AMP were studied in both cells and culture medium. RESULTS: GS significantly reduced PLA2 activity, and more modestly collagenase activity, in the OA chondrocytes in a dose-dependent manner. By contrast, PLA2 and collagenase activity of the culture medium was not modified. No effects on caseinase activity was seen. GS significantly and dose-dependently increased protein synthesis. GS did not modify nitric oxide and cAMP production but significantly increased PKC production. CONCLUSION: GS modified cultured OA chondrocyte metabolism by acting on PKC, cellular PLA2, protein synthesis and possibly collagenase activation. Extrapolation of the effect to the in-vivo situation remains hypothetical but they might represent some possible mechanisms of action of the drug in human.