| 1. |
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| 2. |
- Conaghan, P. G., et al.
(author)
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MRI and non-cartilaginous structures in knee osteoarthritis
- 2006
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:Suppl. 1, s. 87-94
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Journal article (peer-reviewed)abstract
- Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both CIA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful CA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the CA process and its response to therapy. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 3. |
- Englund, M, et al.
(author)
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Patient-relevant outcomes fourteen years after meniscectomy : influence of type of meniscal tear and size of resection
- 2001
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In: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 40:6, s. 631-639
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To study long-term patient-relevant outcomes after meniscectomy, a surgical procedure associated with a high risk of knee osteoarthritis (OA). Principal objectives were to compare traumatic with degenerative meniscal tear and partial with subtotal meniscectomy.METHODS: We studied a well-defined cohort of 205 patients who had undergone isolated unilateral meniscectomy between 1983 and 1985. There was no previous knee surgery and all knees were stable. The type of meniscal tear and surgical resection was ascertained by review of medical records. Patients were followed up after 14 yr (range 12-15 yr) by self-administered questionnaires, one generic [Short Form 36 (SF-36)] and one disease-specific [Knee Injury and Osteoarthritis Outcome Score (KOOS)].RESULTS: In a multivariate analysis, using the Sports and Recreation Function and knee-related Quality of Life subscales of the KOOS questionnaire as dependent variables, patients with a degenerative tear scored significantly worse than individuals with a traumatic tear (P < or = 0.001). When we analysed unmatched subgroups and age- and sex-matched patients with degenerative or traumatic lesions, the same result was found for the knee-specific outcome (P < or = 0.02) and SF-36 except for Social Functioning (P < or = 0.04). There was no difference in outcome for the total cohort according to the type of resection. However, subgroup analyses showed that patients who underwent subtotal meniscectomy for a degenerative tear scored significantly worse on the knee-specific outcome than individuals who had had a partial meniscectomy for the same type of tear (P < or = 0.02).CONCLUSIONS: The long-term outcome of meniscal injury and surgery appears to be determined largely by the type of meniscal tear. Furthermore, our findings support the use of minimal meniscal resection in the treatment of degenerative tears. We suggest that the disease processes associated with the development of OA of the joint cartilage may also be active in the meniscus, and that a tear in a meniscus with degenerative changes might be regarded as the first sign of OA of the joint.
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| 4. |
- Frobell, Richard, et al.
(author)
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The acutely ACL injured knee assessed by MRI: are large volume traumatic bone marrow lesions a sign of severe compression injury?
- 2008
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 16, s. 829-836
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To map by magnetic resonance imaging (MRI) and quantitative MRI (qMRI) concomitant fractures and meniscal injuries, and location and volume of traumatic bone marrow lesions (BMLs) in the acutely anterior cruciate ligament (ACL) injured knee. To relate BML location and volume to cortical depression fractures, meniscal injuries and patient characteristics. METHODS: One hundred and twenty-one subjects (26% women, mean age 26 years) with an ACL rupture to a previously un-injured knee were studied using a 1.5T MR imager within 3 weeks from trauma. Meniscal injuries and fractures were classified by type, size and location. BML location and volume were quantified using a multi-spectral image data set analyzed by computer software, edited by an expert radiologist. RESULTS: Fractures were found in 73 (60%) knees. In 67 (92%) of these knees at least one cortical depression fracture was found. Uni-compartmental meniscal tears were found in 44 (36%) subjects and bi-compartmental in 24 (20%). One hundred and nineteen (98%) knees had at least one BML, all but four (97%) located in the lateral compartment. Knees with a cortical depression fracture had larger BML volumes (P<0.001) than knees without a cortical depression fracture, but no associations were found between meniscal tears and BML volume or fractures. Older age at injury was associated with smaller BML volumes (P<0.01). CONCLUSION: A majority of the ACL injured knees had a cortical depression fracture, which was associated with larger BML volumes. This indicates strong compressive forces to the articular surface and cartilage at the time of injury, which may constitute an additional risk factor for later knee osteoarthritis development.
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| 5. |
- Frobell, Richard, et al.
(author)
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The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year.
- 2009
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; Aug 27, s. 161-167
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS: Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS: JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION: Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.
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| 6. |
- Haapala, J, et al.
(author)
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Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs
- 2001
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 60:1, s. 55-60
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To monitor the concentration of markers of cartilage and synovium metabolism in the knee (stifle) joint synovial fluid of young beagles subjected to immobilisation and subsequent remobilisation.METHODS: The right hind limb of 17 dogs was immobilised in flexion for 11 weeks. Simultaneously, the contralateral left knee was exposed to increased weight bearing. The remobilisation period lasted 50 weeks. Litter mates served as controls. The concentration in joint lavage fluid of interleukin 1 (IL1) was measured by immunoassay, the activity of phospholipase A2 (PLA2) was determined by an extraction method, chondroitin sulphate (CS) concentration by precipitation with Alcian blue, hyaluronan (HA) by an ELISA-like assay using biotinylated HA-binding complexes, matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinases 1 (TIMP-1) by sandwich ELISA, and synovitis was scored by light microscopy.RESULTS: Synovitis or effusion was absent in all experimental and control groups. Immobilisation decreased the joint lavage fluid levels of IL1 (p<0.05), TIMP (p< 0.05), and the concentration of CS down to 38 (p<0.05) in comparison with untreated litter mates with normal weight bearing. Immobilisation did not affect the activity of PLA2, or the concentration of MMP-3 or HA in synovial fluid. Joint remobilisation restored the decreased concentrations of markers to control levels. Increased weight bearing did not change the concentrations of markers in comparison with the control joints with normal weight bearing.CONCLUSIONS: 11 weeks joint immobilisation decreased the concentration of markers of cartilage and synovium metabolism in the synovial fluid, and remobilisation restored the concentrations to control levels. The changes in joint metabolism induced by immobilisation, as reflected by the markers, are thus different from those found in osteoarthritis, where increased levels of these markers are associated with enhanced degradation and synthesis. These findings suggest that the change induced in joint metabolism by immobilisation is reversible in its early stages.
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| 7. |
- Ingvarsson, T, et al.
(author)
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Assessment of primary hip osteoarthritis: comparison of radiographic methods using colon radiographs : comparison of radiographic methods using colon radiographs
- 2000
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 59:8, s. 650-653
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare the reliability of quantitative measurement of minimum hip joint space with a qualitative global assessment of radiological features for estimating the prevalence of primary osteoarthritis (OA) of the hip in colon radiographs.METHODS: All colon radiographs from patients aged 35 or older, taken at three different radiographic departments in Iceland during the years 1990-96, were examined. A total of 3002 hips in 638 men and 863 women were analysed. Intraobserver and interobserver reliability was assessed by measuring 147 randomly selected radiographs (294 hips) twice by the same observer, and 87 and 98 randomly selected radiographs (174 and 196 hips) by two additional independent observers. Minimum hip joint space was measured with a millimetre ruler, and global assessment of radiological features by a published atlas.RESULTS: With a minimum joint space of 2.5 mm or less as definition for OA, 212 hips were defined as having OA. When the global Kellgren and Lawrence assessment with grade 2 (definite narrowing in the presence of definite osteophytes) or higher as definition for OA was used, 202 hips showed OA. However, only 166 hips were diagnosed as OA with both systems. With 2.0 or 3.0 mm minimum joint space as cut off point, the difference between the two methods increased. Both intrarater and interrater reliability was significantly higher with joint space measurement than with global assessment.CONCLUSIONS: Overall prevalence of radiological OA was similar with the two methods. However, the quantitative measurement of minimum hip joint space had a better within-observer and between-observer reliability than qualitative global assessment of radiographic features of hip OA. It is thus suggested that minimum joint space measurement is a preferable method in epidemiological studies of radiological hip OA.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Karlsson, J, et al.
(author)
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Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study
- 2002
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In: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1460-2172. ; 41:11, s. 1240-1248
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Journal article (peer-reviewed)abstract
- Objective. To compare the efficacy and safety of intra-articular injections of two different hyaluronan preparations and placebo in patients with knee osteoarthritis. Methods. In a randomized, patient- and observer-blind, placebo-controlled and multicentre trial with parallel groups, 210 patients, aged 60 yr or above, with knee osteoarthritis were included in a per protocol analysis. The patients were treated with three injections, once weekly, of either native high-molecular-weight hyaluronan (Artzal) or cross-linked hyaluronan (Synvisc) or with placebo and were followed for 52 weeks. The primary efficacy measures were weight-bearing pain during study weeks 026 and the duration of clinical benefit measured with KaplanMeier survival analysis for weeks 052. The secondary outcome measures were resting and maximum pain, Lequesne index, WOMAC (Western Ontario and McMaster University Osteoarthritis Index) and SF-36 (Medical Outcomes Study Short Form Health Survey) scores. Results. The intra-articular injections produced a significant reduction in weight-bearing pain, resting pain, maximum pain and Lequesne and WOMAC scores after 26 weeks. There were no significant differences in outcome between any of the three study groups during the first 26 weeks. In direct comparison against placebo for weeks 052, neither hyaluronan treatment (Artzal or Synvisc) showed a significantly longer duration of clinical benefit than placebo. However, when data for the two hyaluronan-treated groups were pooled, treatment with hyaluronan had a significantly longer duration of benefit compared with placebo (P = 0.047). Conclusion. Patients with knee osteoarthritis who were treated by injection into the knee of either of two hyaluronan preparations or placebo showed clinical improvement during the first 26 weeks of treatment, though neither hyaluronan preparation gave a longer duration of clinical benefit than placebo. However, when data for the two hyaluronan treatments were pooled, there was a significantly longer duration of clinical benefit for hyaluronan treatment than for placebo.
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| 12. |
- Lee, J. H., et al.
(author)
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Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro
- 2009
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In: Osteoarthritis and Cartilage. - 1063-4584. ; 17:5, s. 613-620
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Journal article (peer-reviewed)abstract
- Objective: Resistin is a secreted factor that is elevated in rheumatoid arthritis (RA) and believed to drive joint inflammation in vivo. This study was undertaken to determine if resistin is present in the joint following joint injury and to elucidate the role of resistin in cartilage degradation. Methods: The level of resistin was measured in paired synovial fluid (SF) and serum samples from patients following joint injury (anterior cruciate ligament, ACL or meniscus tear). Localization of resistin was visualized by immunohistochemistry of synovial tissue and cartilage from healthy and CA donors. Mouse and human cartilage cultures were used to assess the effect of resistin on cartilage metabolism. Results: In trauma patients, resistin levels declined with increasing time post injury. The resistin levels were highest in samples collected up to 1 week following traumatic injury (SF: 2980 pg/ml, serum: 7901 pg/ml) and lowest in samples collected 6-26 years post injury (SF: 686 pg/ml, serum: 5682 pg/ml). Resistin was shown to be expressed in macrophage-like cells in both healthy and OA synovial tissue. Treatment of mouse cartilage cultures with recombinant resistin led to a dose dependent loss of proteoglycan and induction of inflammatory cytokine and PGE(2) production. Recombinant resistin inhibited proteoglycan synthesis in human cartilage explants. Conclusion: Resistin is elevated both systemically and locally in the weeks immediately following joint injury and has a direct effect on cartilage matrix turnover and cytokine production. Resistin may play a role in the early stages of trauma-induced CA and may represent a new therapeutic target to slow joint destruction in CA. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 13. |
- Lohmander, L. S., et al.
(author)
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What are the outcomes after joint replacement?
- 2009
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In: EUROHIP: Health Technology Assessment of Hip Arthroplasty in Europe. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783540741336 ; , s. 87-90
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Book chapter (peer-reviewed)abstract
- Total hip replacement (THR) is an effective intervention with a good cost/benefit ratio. Worldwide, each year it brings relief in the form of improved function and decreased pain to at least half a million patients with severe osteoarthritis (OA). Since the introduction by Charnley more than 30 years ago, the basic concept remains much the same, but with a multitude of changes in details of surgical procedure and implant design. Some changes have been introduced after careful testing and controlled trials, many of them without. In spite of this, the experience of most large follow-up series, including the Scandinavian national implant registries, show a gradual improvement in the success rate of THR with increased surgeon experience and improved procedures [7].
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| 14. |
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| 15. |
- McNicholas, M. J., et al.
(author)
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Total meniscectomy in adolescence : A thirty-year follow-up
- 2000
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In: Journal of Bone and Joint Surgery: British Volume. - 0301-620X. ; 82:2, s. 217-221
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Journal article (peer-reviewed)abstract
- We have carried out a prospective, longitudinal 30-year review of 95 adolescents who underwent total meniscectomy in one knee, and have compared the results with those observed 13 years earlier. All the medical records were scrutinized. Of the 63 patients reviewed clinically, 47 reported decreased sporting activity, although subjective satisfaction rose by 3% to 71%. The scores on the WOMAC ostcoarthritis index differed significantly between patients grouped by subjective global assessment. Satisfactory function scores increased from 48% to 60%. In the 53 patients consenting to bilateral radiography of the knee, the incidence of narrowing of the articular cartilage in the operated knee increased significantly between the reviews (19% to 36%). Progression of degenerative change paralleled reduction in activity. Outcome measures were best after medial, intermediate after lateral and worst after double meniscectomy.
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| 16. |
- Nilsdotter, A-K, et al.
(author)
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Predictors of patient relevant outcome after total hip replacement for osteoarthritis : a prospective study
- 2003
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 62:10, s. 30-923
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate prospectively long term patient relevant outcomes after unilateral total hip replacement (THR) for osteoarthritis (OA). To identify non-responders to this intervention and patient related predictors of unsatisfactory outcome.METHODS: A case-control study comparing health related quality of life of 219 patients (mean age 71) after THR with that of a matched reference group of 117 subjects without hip complaints recruited from the community. Patients and reference group answered SF-36 and WOMAC questionnaires preoperatively, at 3, 6, 12 months, and at 3.6 years (range 26-65 months) postoperatively. Supplementary questions were asked at the final follow up.RESULTS: 198/211 (94%) of the patients and 83/109 (76%) of the reference group participated at the final follow up. At follow up, the only difference between the two groups in the SF-36 was physical function, where patients scored worse. Patients also reported worse WOMAC function. 31% of the patients had improved by <10/100 WOMAC score points for pain and/or function at final follow up, compared with preoperatively. More pain preoperatively and higher age and postoperative low back pain predicted a worse outcome in WOMAC function.CONCLUSION: 3.6 years after THR for OA, health related quality of life was similar for patients and reference group except for function, where patients had worse function. Higher age and more pain preoperatively predicted a poor outcome. Patients with hip OA with musculoskeletal comorbidities, such as low back pain and OA of the non-operated hip, have less long term functional improvement after THR.
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| 17. |
- Pendleton, A., et al.
(author)
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EULAR recommendations for the management of knee osteoarthritis : Report of a task force of the standing committee for international clinical studies including therapeutic trials (ESCISIT)
- 2000
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967. ; 59:12, s. 44-936
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Journal article (peer-reviewed)abstract
- Background - Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. Methods - The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, meta-analyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. Results - Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. Conclusions - These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities. It is apparent that certain clinical propositions are supported by substantial research based evidence, while others are not. There is thus an urgent need for future well designed trials to consider key clinical questions.
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| 18. |
- Pendleton, A., et al.
(author)
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EULAR-Richtlinien für die Behandlung von Kniegelenksarthrose : Bericht der Arbeitsgruppe des Standing Committees for International Clinical Studies Including Therapeutic Trials (ESCISIT)
- 2003
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In: Journal fur Mineralstoffwechsel. - 1023-7763. ; 10:3, s. 23-31
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Journal article (peer-reviewed)abstract
- Background: Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. Methods: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, metaanalyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. Results: Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the eVects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. Conclusions: These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities. It is apparent that certain clinical propositions are supported by substantial research based evidence, while others are not. There is thus an urgent need for future well designed trials to consider key clinical questions.
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| 19. |
- Pratta, M. A., et al.
(author)
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Development and characterization of a highly specific and sensitive sandwich ELISA for detection of aggrecanase-generated aggrecan fragments
- 2006
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:7, s. 702-713
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Journal article (peer-reviewed)abstract
- Objective: To develop an enzyme linked immunosorbent assay (ELISA) to quantify the levels of specific aggrecan fragments generated by aggrecanase-mediated cleavage at the (373)Glu-(374)Ala bond within the aggrecan interglobular domain. Methods: The ELISA employs a commercially available monoclonal antibody to capture aggrecan fragments containing keratan sulfate (KS). Aggrecan fragments generated by cleavage at the Glu-Ala bond were then detected using a monoclonal neoepitope antibody (mAb OA-1) that specifically recognizes the N-terminal sequence 'ARGSVIL'. Results: The mAb OA-1 antibody was highly specific for the immunizing neoepitope peptide since neither peptides spanning the cleavage site nor mutated peptides were detected. Aggrecan fragments generated by ADAMTS-4 digested human aggrecan monomers and from IL-1-stimulated human cartilage explants were quantified by the ELISA, and we observed increased sensitivity of the ELISA compared to mAb OA-1 Western analysis. We also observed that the basal, as well as IL-1-stimulated production of ARGS aggrecan fragments from human articular cartilage explants was blocked by a selective aggrecanase inhibitor, consistent with generation of the ARGS neoepitope in human articular cartilage being mediated by aggrecanase. Using purified human aggrecan digested by ADAMTS-4 as standard to quantify ARGS aggrecan fragments in human synovial fluids, we determined that the calculated amount of ARGSVIL-aggrecan fragments by ELISA measurement is in agreement with the published levels of these fragments, supporting its potential utility as a biomarker assay for osteoarthritis. Conclusion: We have developed an assay that detects and quantifies specific aggrecan fragments generated by aggrecanase-mediated cleavage. Because aggrecanase mediates degradation of human articular aggrecan in joint disease, the KS/mAb OA-1 ELISA may serve as a biomarker assay for evaluation of preclinical and clinical samples. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 20. |
- Struglics, André, et al.
(author)
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Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments.
- 2006
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:2, s. 101-113
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Journal article (peer-reviewed)abstract
- Objective: To identify the major aggrecanase-and matrix metalloproteinase (MMP)-generated aggrecan fragments in human osteoarthritis (OA) synovial fluid and in human OA joint cartilage. Method Aggrecan fragments were prepared by CsCl gradient centrifugation. Fragment distributions were compared with aggrecanase-1 (ADAMTS-4) and MMP-3 digested human aggrecan by analysis with neoepitope antibodies and an anti-G1 domain antibody, using Western immuno-blots. Results: The overall fragment pattern of CA synovial fluid aggrecan was similar to the fragment pattern of cartilage aggrecan cleaved in vitro by ADAMTS-4. However, multiple glycosaminoglycan (GAG) containing aggrecanase and MMP-generated aggrecan fragments were identified in OA synovial fluid and some of these fragments were produced by the action of both types of proteinases. The synovial fluid content of large size aggrecan fragments with (374)ARGS- and (342)FFGV-N-terminals was about 107 and 40 pmoles per ml, respectively, out of a total concentration of aggrecan fragments of about 185 pmoles per ml. CA synovial fluid contained insignificant amounts of the G1-IPEN341 fragment as compared to the G1-TEGE(373) fragment, while CA cartilage contained significant amounts of both fragments. OA cartilage contained several GAG-containing aggrecan fragments with N-terminals of G1- or (342)FFGV- but no fragments with an N-terminal of (374)ARGS-. Conclusions: The overall pattern of aggrecan fragments in human CA synovial fluid and cartilage supports an important role for aggrecanase in aggrecan degradation. However, the fragment patterns and their differential distribution between cartilage and synovial fluid are consistent with the existence of at least two proteolytic pathways for aggrecan degradation in human OA, generating both (342)FFGV- and (374)ARGS-fragments. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 21. |
- Zhang, W., et al.
(author)
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EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT
- 2009
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:1, s. 8-17
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Research review (peer-reviewed)abstract
- Objectives: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. Results: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR,10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. Conclusion: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
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| 22. |
- Zhang, W., et al.
(author)
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EULAR evidence based recommendations for the management of hand osteoarthritis: report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT)
- 2007
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 66:3, s. 377-388
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Journal article (peer-reviewed)abstract
- Objectives: To develop evidence based recommendations for the management of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. Results: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. Conclusion: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.
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