Multicentre, prospective, open study to evaluate the safety and efficacy of hylan G-F 20 in knee osteoarthritis subjects presenting with pain following arthroscopic meniscectomy

The aim of the study was to evaluate the safety and efficacy of viscosupplementation with hylan G-F 20 in patients with mild to moderate osteoarthritis (OA) presenting with persistent knee pain 4–12 weeks after arthroscopic meniscectomy. A prospective, multi-centre, open study was carried out in patients with pain due to OA of the knee, not resolved by simple analgesics, 4–12 weeks after undergoing arthroscopic meniscectomy. To be eligible, patients had to score ≥50 mm and ≤90 mm on both walking pain and patient global assessment visual analogue scales (VAS; 0–100 mm) at baseline and be radiologically diagnosed pre-operatively with OA grade I or II on the Kellgren-Lawrence scale, with <50% joint space narrowing. Patients received three intra-articular, 2 ml injections of hylan G-F 20 in the target knee with an interval of 1 week between injections, and were followed for 52 weeks. The primary efficacy endpoint was the change from baseline in the walking pain VAS score at 26 weeks. Secondary outcome measures were the walking pain VAS scores at all other time points, the WOMAC Index at all time points, and patient and physician global assessment at all time points. The safety of the treatment was assessed using adverse event (AE) reports. A total of 62 patients (mean age 55.4 years, 52% male) were enrolled. The mean walking pain VAS score decreased by 36.8 mm from baseline at 26 weeks (P < 0.0001), and also showed statistically significant decreases (P < 0.0001) at all other time points. The change in WOMAC total and subscale scores from baseline were statistically significant (P < 0.0001) at all time points, as were the decreases in the physician and patient global assessment VAS scores. There were 18 target knee AEs (mostly pain and/or swelling and/or effusion) in 12 patients (19%) considered to be at least possibly related to treatment. The majority of these (78%) were mild or moderate in intensity. One patient (1.6%) experienced a serious adverse event (synovitis) in the target knee that was considered possibly related to study treatment. Hylan G-F 20 provides effective pain relief and improves stiffness and physical function in patients with mild to moderate OA presenting with persistent osteoarthritic pain 4–12 weeks after arthroscopic meniscectomy. Symptomatic efficacy was maximised at 12 weeks and maintained at 26 and 52 weeks. The type (pain and/or swelling and/or effusion) and the intensity (mostly mild/moderate) of AEs reported in this study are similar to those reported in other trials in different patient populations, but the incidence was higher (19%). The risk/benefit of hylan G-F 20 in this particular population of patients is favourable

Value of biomarkers in osteoarthritis: Current status and perspectives

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

Radiographic joint space narrowing in osteoarthritis of the knee: relationship to meniscal tears and duration of pain

[[abstract]]Objective The objective of this study was to assess, with knee radiography, joint space narrowing (JSN) and its relationship to meniscal tears, anterior cruciate ligament (ACL) ruptures, articular cartilage erosion, and duration of pain in patients with knee osteoarthritis. Materials and methods A total of 140 patients who had knee osteoarthritis and underwent primary total knee replacement (TKR) surgery, with unicompartmental medial tibiofemoral JSN (grade 1 or greater) and normal lateral compartments, were recruited. Polytomous logistic regression was used to assess the relationship between JSN and risk factors. Results All patients with JSN were categorized as grade 1 (n = 14, 10.0%), grade 2 (n = 64, 45.7%), or grade 3 (n = 62, 44.3%). Women presented with indications for a TKR at a younger age than men (mean age, 69 vs 73 years, P < 0.05). There were 123 (87.9%) meniscal tears and 58 (41.4%) partial (insufficient or attenuated ACL fibers) and 10 (7.1%) complete ACL ruptures; 115 of 134 (85.8%) patients had moderate to severe cartilage erosion. A higher grade of JSN was correlated with a higher frequency of meniscal tears [odds ratio (OR) 6.00, 95% CI 1.29–27.96 for grade 2 vs grade 1 JSN] and duration of knee pain (OR 1.25, 95% CI 1.01–1.53 for grade 3 vs grade 1 JSN). A higher grade of JSN was not correlated with a higher frequency of ACL rupture or articular cartilage erosion. Conclusion A higher grade of JSN is associated with a higher frequency of meniscal tears and long duration of knee pain in patients with knee osteoarthritis.[[incitationindex]]SCI[[booktype]]紙

Radiographic assessment of the femorotibial joint of the CCLT rabbit experimental model of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas.</p> <p>Methods</p> <p>In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits.</p> <p>Results</p> <p>Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (r_s= 0.68 and r_s= 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (r_s= 0.64, p < 0.001).</p> <p>Conclusion</p> <p>Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.</p

What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis?

Knee osteoarthritis is associated with structural changes in the joint. Despite its many drawbacks, radiography is the current standard for evaluating joint structure in trials of potential disease-modifying osteoarthritis drugs. MRI is a non-invasive alternative that provides comprehensive imaging of the whole joint. Frequently used MRI measurements in knee osteoarthritis are cartilage volume and thickness; others include synovitis, synovial fluid effusions, bone marrow lesions (BML) and meniscal damage. Joint replacement is considered a clinically relevant outcome in knee osteoarthritis; however, its utility in clinical trials is limited. An alternative is virtual knee replacement on the basis of symptoms and structural damage. MRI may prove to be a good alternative to radiography in definitions of knee replacement. One of the MRI parameters that predicts knee replacement is medial compartment cartilage volume/thickness, which correlates with radiographic joint space width, is sensitive to change, and predicts outcomes in a continuous manner. Other MRI parameters include BML and meniscal lesions. MRI appears to be a viable alternative to radiography for the evaluation of structural changes in knee osteoarthritis and prediction of joint replacement

The effectiveness of pulsed electrical stimulation (E-PES) in the management of osteoarthritis of the knee: a protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) of the knee is one of the main causes of musculoskeletal disability in the western world. Current available management options provide symptomatic relief (exercise and self-management, medication and surgery) but do not, in general, address the disease process itself. Moreover, adverse effects and complications with some of these interventions (medication and surgery) and the presence of co-morbidities commonly restrict their use. There is clearly a need to investigate treatments that are more widely applicable for symptom management and which may also directly address the disease process itself.</p> <p>In two randomised controlled trials of four and 12 weeks duration, pulsed electrical stimulation was shown to be effective in managing the symptoms of OA of the knee. Laboratory and animal studies demonstrate the capacity of externally applied electric and electromagnetic fields to positively affect chondrocyte proliferation and extracellular matrix protein production. This latter evidence provides strong theoretical support for the use of electrical stimulation to maintain and repair cartilage in the clinical setting and highlights its potential as a disease-modifying modality.</p> <p>Methods/Design</p> <p>A double-blind, randomised, placebo-controlled, repeated measures trial to examine the effectiveness of pulsed electrical stimulation in providing symptomatic relief for people with OA of the knee over 26 weeks.</p> <p>Seventy people will be recruited and information regarding age, gender, body mass index and medication use will be recorded. The population will be stratified for age, gender and baseline pain levels.</p> <p>Outcome measures will include pain (100 mm VAS and WOMAC 3.1), function (WOMAC 3.1), stiffness (WOMAC 3.1), patient global assessment (100 mm VAS) and quality of life (SF-36). These outcomes will be measured at baseline, four, 16 and 26 weeks. Activity levels will be measured at baseline and 16 weeks using accelerometers and the Human Activity Profile questionnaire. A patient global perceived effect scale (11-point Likert) will be completed at 16 and 26 weeks.</p> <p>Discussion</p> <p>This paper describes the protocol for a randomised, double-blind, placebo-controlled trial that will contribute to the evidence regarding the use of sub-sensory pulsed electrical stimulation in the management of OA of the knee.</p> <p>Trial registration</p> <p>Australian Clinical Trials Registry ACTRN12607000492459.</p