MMP-3 in the peripheral serum as a biomarker of knee osteoarthritis, 40 years after open total knee meniscectomy.

BACKGROUND: To explore potential biomarkers in a meniscectomy-induced knee osteoarthritis model, at forty years after meniscectomy. METHODS: We carried out a forty-year study of 53 patients who, as adolescents, underwent open total meniscectomy and assessed two potential synovial and serum biomarkers, namely glycosaminoglycan (GAG) and matrix metalloproteinase-3 (MMP-3). Of the 30 patients available for review, 8 had contralateral knee operations and were excluded. Of the remaining 22 patients, 17 had successful operated knee synovial fluid aspirations and 8 also had successful contralateral control knee aspirations. GAG and MMP3 levels in the synovial fluid and peripheral serum was measured using Alcian blue precipitation and ELISA quantification, respectively. Patients also had their knee radiographs assessed and their radiographic osteoarthritis classified as per the Kellgren-Lawrence and Ahlbӓck systems. RESULTS: At forty years after meniscectomy, synovial MMP-3 levels remain increased (p = 0.0132) while GAG levels were reduced (p = 0.0487) when compared to controls and these two levels correlate inversely. Furthermore, levels of synovial MMP-3 significantly correlated (p = 0.0032, r = 0.7734; p = 0.0256, r = 0.5552) and GAG levels significantly inversely correlated (p = 0.0308, r = - 0.6220; p = 0.0135, r = - 0.6024), respectively, with both radiological scoring systems. Interestingly, we found that the levels of serum MMP-3 correlated only with the synovial fluid levels of MMP-3 in the operated knee and not with the non-operated joint (p = 0.0252, r = 0.7706 vs. p = 0.0764, r = 0.6576). Multiple regression analysis for patient's quality of life based on these biomarkers revealed an almost perfect result with an R2 of 0.9998 and a p value = 0.0087. CONCLUSION: Our results suggest that serum levels of MMP3 could be used as a potential biomarker for knee osteoarthritis, using a simple blood test. Larger cohorts are desirable in order to prove or disprove this finding

Is increased joint loading detrimental to obese patients with knee osteoarthritis? A secondary data analysis from a randomized trial

SummaryObjectiveTo investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA).MethodsData from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into ‘Unloaders’ (participants that reduced joint loads) and ‘Loaders’ (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period.Results157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: −2.4 KOOS points [95% CI −6.8:1.9]) and cartilage loss (group difference: −0.06 BLOKS points [95% CI −0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders.ConclusionFor obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads.Clinicaltrials.govNCT00655941

Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs

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

Differential patterns of PMN-elastase and type III procollagen peptide in knee joint effusions due to acute and chronic sports injuries

In 38 traumatic knee joint effusions the proteolytic enzyme PMN-elastase (PMN-E) and the repair marker procollagen III aminoterminal peptide (PIIINP) were determined. According to the period between trauma and first aspiration of the effusion, the patients were divided into 3 groups. Group I (17 patients; period between trauma and first aspiration not longer than 72 hours) showed high concentrations of PMN-E (up to 5400 ng/ml) and low concentrations of PIIINP (<13 U/ml). Group II (11 patients; aspiration within 4 to 14 days) had mean PMN-E and PIIINP concentrations of 125.6 ng/ml and 52.1 U/ ml, respectively. In group III (10 patients, aspiration after 14 days) mean PMN-E concentration was 123.8 ng/ml and mean PIIINP concentration was 63.4 U/ml. Graphic depiction of PMN-E and PIIINP levels in each individual sample as a function of time between trauma and fluid collection revealed highly increasing PMN-E levels during the first 24 posttraumatic hours, followed by rapidly decreasing levels within 72 hours post trauma, and no change after the 4th posttraumatic day. In contrast, PIIINP increased continuously up to the first posttraumatic week and stayed at high levels up to 90 days (end of the observation period). The differential patterns of PMN-E and PIIINP concentration in knee joint effusions may be useful in estimating the period between trauma and first treatment (aspiration of effusion) and should, therefore, be helpful in detecting degenerative lesions, which seem to be characterized by low PMN-E concomitantly with high PIIINP levels

Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone

The original publication is available at www.springerlink.comNon peer reviewedPostprin

A 2-year prospective study of patient-relevant outcomes in patients operated on for knee osteoarthritis with tibial osteotomy

BACKGROUND: Tibial osteotomy is a treatment for younger and/or physically active patients suffering from uni-compartmental knee osteoarthritis. The open wedge osteotomy by the hemicallotasis technique includes the use of external fixation. The use of external fixation has several advantages, as early mobilization and the opportunity for optimal correction. However, the hemicallotasis technique has also been described as a cumbersome procedure for the patient. The aim of this study was to prospectively evaluate patient-relevant outcomes during the first 2 post-operative years. Especially the treatment period, during which external fixation was used, was closely monitored. METHODS: In an uncontrolled study, fifty-eight consecutive patients, 30 men and 28 women (mean age 54 years) were operated on by the hemicallotasis technique were evaluated with the patient-relevant outcome measure Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively, during the treatment with external fixation, one week after removal of the external fixation, at 6 months, and at one and two years postoperatively. RESULTS: At the 2-year postoperative follow-up, all subscales of the KOOS were improved (p < 0.001), mostly in pain (41–80 on a 0–100 worst to best scale) and knee-related quality of life (21–61 on a 0–100 worst to best scale), compared to the preoperative status. Significant improvements in pain and other symptoms, function of daily life and quality of life were seen already during the treatment period (mean 98 ± 18 days) with the external fixation. More demanding functions such as kneeling, squatting, jumping and running, were improved first after extraction of the external fixation device and the pins. CONCLUSION: Tibial osteotomy by the hemicallotasis technique yields large improvement in self-rated pain, function and quality of life, which persists over two years. Surprisingly, large improvements occurred already during the immediate post-operative period when the external fixation was still used

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil