What can we do about osteoarthritis?

Osteoarthritis is complex in genetics, pathogenesis, monitoring and treatment. Current treatment of osteoarthritis does not influence progression. Much could be gained by more effective 'low-tech-low-cost' treatment. However, many patients have rapidly progressive disease, multiple joint involvement, and severe disease. We need to clarify the genetics of osteoarthritis, identify those at risk for progression and severe disease, and identify molecular processes critical for joint survival and failure. Will saving the cartilage improve patient pain and function? Effective outcome measures are needed to accelerate testing of new treatments. Further improvement is needed in joint implant technology to decrease costs, wear and loosening

Patient Relevant Outcomes after total hip replacement. A comparison between different surgical techniques

OBJECTIVE: To investigate differences in pre- and postoperative patient-relevant outcome between hybrid total hip replacement (THR) and cemented THR in patients with primary osteoarthritis (OA). METHODS: 245 consecutive patients were included in the study. 68 of the patients (mean age 62) were operated on with hybrid THR and 177 (mean age 74) were operated on with cemented THR. All patients were investigated preoperatively and 0.5, 1 and 3.6 years postoperatively with two self-administered questionnaires, SF-36 and WOMAC (Western Ontario and MacMaster Universities Osteoarthritis Index, LK 3.0). RESULTS: Preoperatively, there was a difference in the SF-36 subscales RP (role physical) and GH (general health) where the patients with the hybrid THR attained better scores. At 3.6-years the patients with the hybrid THR reached better scores in all SF-36 subscales except BP (bodily pain) and GH. Further, they had better scores in WOMAC function. However, after adjusting for age, sex, follow-up time and baseline values there were no differences in outcome between the two different surgical techniques. CONCLUSION: This medium term (3–5 years), controlled, open cohort study, using patient-relevant outcome measures, did not reveal any differences between hybrid THR and cemented THR for OA at 3.6 years after surgery. Since the study had 75–94% power to detect the clinically significant score difference of 10 points, we suggest that any difference in outcome between these two methods is small and may require a large-scale, blinded, randomized trial to show

The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis

The Knee injury and Osteoarthritis Outcome Score (KOOS) was developed as an extension of the WOMAC Osteoarthritis Index with the purpose of evaluating short-term and long-term symptoms and function in subjects with knee injury and osteoarthritis. The KOOS holds five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS has been validated for several orthopaedic interventions such as anterior cruciate ligament reconstruction, meniscectomy and total knee replacement. In addition the instrument has been used to evaluate physical therapy, nutritional supplementation and glucosamine supplementation. The effect size is generally largest for the subscale QOL followed by the subscale Pain. The KOOS is a valid, reliable and responsive self-administered instrument that can be used for short-term and long-term follow-up of several types of knee injury including osteoarthritis. The measure is relatively new and further use of the instrument will add knowledge and suggest areas that need to be further explored and improved

Synovial fluid level of aggrecan ARGS fragments is a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels: a cross-sectional study

Introduction Aggrecanase cleavage at the (392)Glu-(393)Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal (393)ARGS fragments, is an early key event in arthritis and joint injuries. Here, we use a quantitative immunoassay of aggrecan ARGS neoepitope fragments in human synovial fluid to determine if this cleavage-site specific method better identifies joint pathology than previously available less specific aggrecan assays. Methods Synovial fluid (SF) from 26 people with healthy knees (reference) and 269 patients were analyzed in a cross-sectional study. Patient groups were acute inflammatory arthritis, acute knee injury, chronic knee injury and knee osteoarthritis (OA). Aggrecan ARGS fragments were assayed by ELISA using the monoclonal antibody OA-1. Total aggrecan content was analyzed by an ELISA using the monoclonal antibody 1-F21, and sulfated glycosaminoglycan by Alcian blue precipitation. Results Aggrecan ARGS fragment concentrations in all groups differed from the reference group (P < 0.001). The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group. Median levels (in pmol ARGS/ml SF) were: reference 0.5, acute inflammatory arthritis 88.5, acute knee injury 53.9, chronic knee injury 0.5 and OA 4.6. In contrast, aggrecan and sulfated glycosaminoglycan concentrations varied much less between groups, and only acute inflammatory arthritis and acute knee injury were found to have a two-fold increase in median levels compared to the reference. Conclusions Levels of aggrecan ARGS fragments in human synovial fluid are increased in human arthritis, OA and after knee injury, likely reflecting an enhanced cleavage at the (392)Glu-(393)Ala bond in the IGD by aggrecanase. An assay that specifically quantified these fragments better distinguished samples from joints with pathology than assays monitoring aggrecan or glycosaminoglycan concentrations. The newly developed ARGS fragment assay can be used to monitor aggrecanase activity in human joint disease and experimental models

Association between synovial fluid levels of aggrecan ARGS fragments and radiographic progression in knee osteoarthritis

INTRODUCTION: Aggrecanase cleavage at the (392)Glu-(393)Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal (393)ARGS fragments, is an early key event in arthritis and joint injuries. We determined whether synovial fluid (SF) levels of ARGS-aggrecan distinguish subjects with progressive radiographic knee osteoarthritis (ROA) from those with stable or no ROA. METHODS: We studied 141 subjects who, at examination A, had been given meniscectomies an average of 18 years earlier (range, 15 to 22 years). Seventeen individuals without surgery, and without known injury to the menisci or cruciate ligaments, were used as references. At examinations A and B, with a mean follow-up time of 7.5 years, we obtained SF and standing tibiofemoral and skyline patellofemoral radiographs. SF ARGS-aggrecan was measured with an electrochemiluminescence immunoassay, and we graded radiographs according to the OARSI atlas. The association between SF ARGS levels at examination A and progression of radiographic features of knee OA between examinations A and B was assessed by using logistic regression adjusted for age, gender, body mass index, and time between examinations, and stratified by ROA status at examination A. RESULTS: We found a weak negative association between SF ARGS concentrations and loss of joint space: the likelihood of progression of radiographic joint space narrowing decreased 0.9 times per picomole per milliliter increase in ARGS (odds ratio (OR) 0.89; 95% confidence interval (CI), 0.79 to 0.996). In subjects with and without preexisting ROA at examination A, the association was OR, 0.96; 0.81 to 1.13; and 0.77; 0.62 to 0.95, respectively. Average levels of SF ARGS 18 years after meniscectomy were no different from those of reference subjects and were not correlated to radiographic status at examination A. CONCLUSIONS: In subjects with previous knee meniscectomy but without ROA, levels of SF ARGS-aggrecan were weakly and inversely associated with increased loss of joint space over a period of 7.5 years

Coculture of bovine cartilage with synovium and fibrous joint capsule increases aggrecanase and matrix metalloproteinase activity

Background A hallmark of osteoarthritis is increased proteolytic cleavage of aggrecan. Cross talk between cartilage and the synovium + joint capsule (SJC) can drive cartilage degradation by activating proteases in both tissues. We investigated aggrecan proteolysis patterns in cartilage explants using a physiologically relevant explant model of joint injury combining cartilage mechanical compression and coincubation with SJC. Methods Bovine cartilage explants were untreated; coincubated with SJC; or subjected to mechanical injury and coincubated with SJC, mechanical injury alone, or mechanical injury and incubated with tumor necrosis factor-α (TNF-α). To compare the patterns of aggrecan proteolysis between 6 h and 16 days, release of sulfated glycosaminoglycans and specific proteolytic aggrecan fragments into medium or remaining in cartilage explants was measured by dimethylmethylene blue and Western blot analysis. Results Aggrecanase activity toward aggrecan was observed in all conditions, but it was directed toward the TEGE↓ARGS interglobular domain (IGD) site only when cartilage was coincubated with SJC or TNF-α. Matrix metalloproteinase (MMP) activity at the aggrecan IGD site (IPES↓FFGV) was not detected when cartilage was exposed to TNF-α (up to 6 days), but it was in all other conditions. Compared with when bovine cartilage was left untreated or subjected to mechanical injury alone, additional aggrecan fragment types were released into medium and proteolysis of aggrecan started at an earlier time when SJC was present. Conclusions Indicative of different proteolytic pathways for aggrecan degradation, the SJC increases both aggrecanase and MMP activity toward aggrecan, whereas TNF-α inhibits MMP activity against the IGD of aggrecan.National Institutes of Health (U.S.) (AR060331

Revision and complication rates in 654 Exeter total hip replacements, with a maximum follow-up of 20 years.

To access full text version of this article. Please click on the hyperlink "View/open" at the bottom of this pageBACKGROUND: Iceland's geographical isolation with a stable and small population gives a rare opportunity for follow-up studies of medical interventions. Total hip replacements (THR) have been done at FSA Central Hospital in Akureyri, Iceland since 1982 with the Exeter hip implant being in use from the beginning. METHODS: Hospital records for all patients operated on with THR between 1982 and the end of 1999 were reviewed and the patients were followed until the end of 2001. Information was gathered regarding the indication for primary surgery, the reason for revision if needed, as well as that of any complications. Survival statistics were used to calculate the cumulative revision rate. RESULTS: The mean age at primary THR was 68.4 years for males and 68.8 years for females. 654 primary THRs were done; of which 571 (87 %) were due to osteoarthritis. 37 of the primary arthroplasties had been revised before the end of year 2001. CONCLUSION: We have in this unique 2-20 year study of 654 THRs with no loss to follow-up for the patients, found revision rates that conform with the large Swedish THR registry. Complication rates in general are in agreement with that reported for other comparable patient groups, while infection rates appear lower

The complement system is activated in synovial fluid from subjects with knee injury and from patients with osteoarthritis

Concentrations of C4d, C3bBbP and sTCC in synovial fluid. (DOCX 37 kb