A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. Comparative evaluation of autologous chondrocyte implantation and mosaicplasty: a multicentered randomized clinical trial. Intra-articular hyaluronic acid in osteoarthritis of the knee: an investigation into mechanisms of action. The relationship between the outcome of studies of autologous chondrocyte implantation and the presence of commercial funding. Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up. High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Hylan G-F 20 efficacy on articular cartilage quality in patients with knee osteoarthritis: clinical and MRI assessment. Epidemiology of research into interventions for the treatment of osteoarthritis of the knee joint. Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study.
Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm2. The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26). Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed. Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value. To compare the respective performance and effectiveness of autologous chondrocyte implantation (ACI) and mosaicplasty at resurfacing local full-thickness chondral defects of the knee.
                Randomized clinical trial.
                Multicenter trial at orthopedic clinics and university hospitals conducted from 1997 to 2000.
                A population of patients selected according to eligibility criteria of age, traumatic origin of the defect, its localization, size, and gravity, and above all, no previous surgical treatment of the lesion. Forty-seven patients were randomly assigned to ACI or mosaicplasty and subjected to arthroscopic debridement of the lesion at the time of enrollment. They were called for surgery 6 months after the initial debridement.
                Improved knee functionality as assessed by repeated clinical evaluation based on the International Knee Documentation Committee Scale and the Lysholm Knee Scoring Scale.
                Fourteen patients (31.8%) experienced substantial improvement following the initial debridement and, being clinically cured, received no further treatment. Seven patients (15.9%) were lost to follow-up. Among the 23 patients (52.3%) who could effectively be evaluated, a complete recovery (ie, Lysholm Knee Scoring Scale score, 90-100) was observed upon clinical examination in 88% of the mosaicplasty-treated patients and in 68% of the ACI-treated ones (P = 0.093).
                Although the low power of our study prevents definitive conclusions, ACI and mosaicplasty are cartilage repair techniques that are clinically equivalent and similar in performance. The high percentage of spontaneous improvement ((1/3) of the patients) observed after simple debridement calls into question the need for prompt surgical treatment of patients with lesions similar to those included in this clinical trial. Moreover, this finding warrants further investigation, ideally through randomized clinical trials in which patients subjected to debridement alone are compared with patients undergoing reconstructive surgery. The objective of this study was to investigate mechanisms of action of intra-articular hyaluronic acid in osteoarthritis (OA) of the knee. Twelve patients with bilateral knee OA and synovial effusions entered a randomized, single-blind, blind observer study. Hyaluronic acid ("Hyalgan", Fidia SpA, Italy) or placebo were given by intra-articular injection weekly for 5 weeks. Assessments included clinical indices and imaging (magnetic resonance imaging (MRI) and 99m Tc bone scanning) before and after the course of injections. In addition, synovial fluid keratan sulfate (KS), chondroitin sulfate (CS) and C-propeptide of type II collagen (CPII) were measured. MRI and 99m Tc scanning showed no change in either treated or placebo knees over the 6-week study period. A fall in KS levels occurred in treated knees compared with placebo (Wilcoxon paired test, P = 0.1), although this did not reach significance perhaps due to small sample numbers). Ten out of 12 treated knees showed a fall in KS, compared with four out of 12 placebo knees. CS and CPII levels did not change significantly. Intra-articular injection of hyaluronic acid did not result in any improvement in the clinical indices compared to the placebo. In conclusion, assessment of cartilage markers may be of value when studying novel therapies in OA. MRI appearances remain remarkably stable over a 6-week period. Autologous chondrocyte implantation (ACI) is an expensive treatment option for focal cartilage defects, and commercial funding of research is associated with a study reaching a positive conclusion. The purpose of this analysis is to compare outcomes (and levels of evidence) between published ACI outcome studies that were commercially funded and studies that were not commercially funded.
                Commercially funded ACI literature could be commercially biased.
                Comparative meta-analysis.
                MEDLINE was searched for human, knee, ACI, nonmembrane, English language, and clinical outcome studies. Studies were evaluated with regard to funding status (commercially funded or not commercially funded), outcomes, and levels of evidence. Outcomes and levels of evidence were evaluated and compared for commercially funded studies versus those that were not commercially funded.
                Twenty-three studies were included; 16 (70%) were commercially funded. Pooled clinical outcome measures data were not significantly different (Lysholm, Modified Cincinnati, patient-reported Cincinnati, Tegner, pain Visual Analog Scale) when comparing commercially funded studies with those that were not commercially funded. However, distribution of levels of evidence was significantly lower (P = .045) for commercially funded studies.
                Reassuringly, commercial funding of ACI studies did not result in a difference in published clinical outcomes versus those that were not commercially funded. However, the lower levels of evidence of commercially funded studies suggests that commercially funded ACI studies may be of less value to surgeons desiring to practice evidence-based medicine, and, in the future, commercial entities funding medical research could selectively fund studies of the highest levels of evidence. The goal of this study was to determine whether hyaluronic acid (HA) or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for HA and PE patients improved from 62.6 +/- 13.8 to 88.8 +/- 11.1 and from 65.4 +/- 12.3 to 88.3 +/- 9.1, respectively, at the end of the trial (P < 0.01). There were no statistically significant differences between the groups. Twenty-one patients of the HA group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement from 57.0 +/- 12.9 to 76.7 +/- 11.9 (P < 0.01). This prospective randomized trial confirmed that both HA injections and PE result in functional improvement. HA injections also increase the levels of satisfaction of the OA patients. Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee. The aim of this study was to investigate the effects of intra-articular hyaluronic acid (HA) on symptoms, functional outcome, and changes in articular cartilage assessed by magnetic resonance imaging (MRI) in patients with knee osteoarthritis. Thirty patients were randomly assigned to treatment with HA (hylan G-F 20, Synvisc) or saline. The treatment group consisted of 20 patients receiving three weekly injections of HA into one or both knees (30 knees). The control group consisted of ten patients receiving three intra-articular injections of 2 ml saline at the same intervals (ten knees). To determine the effectiveness of the HA therapy, all patients were assessed prior to the injections (baseline) and after the 1st, 2nd, 3rd, and 8th weeks. Assessment comprised the following: pain at rest, at night, and on walking using a visual analogue scale (VAS); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function scores; 15-m walking time; need for analgesics; and evaluation of treatment by the patients. MRI of patellofemoral (PF) articular cartilage was also examined before and after the course of injections at the 8th week. When compared to placebo, a significant statistical difference was found in all clinical parameters. On MRI, although the difference in the PF joint cartilage quality in the HA group before and after the treatment was statistically significant (p < 0.05), this significance was not detected between the groups after the treatment (p > 0.05). After the HA injections, a significant analgesic effect was seen as early as the 3rd week continuing up to the 8th week and functional improvement was seen at the 8th week. In conclusion, intra-articular injections of HA is an effective choice of treatment in patients with knee osteoarthritis. To assess the published research base for interventions for osteoarthritis of the knee, and to identify areas in need of further research.
                Literature searches were conducted on electronic databases (Medline, Embase, ISI, and Cochrane library), bibliographies of existing review articles were hand searched, and a postal questionnaire was sent to members of the Osteoarthritis Research Society International. All relevant articles were copied and searched for treatment type, study methodology, statistical results, conclusions, funding source, researcher affiliations, and year of publication, using a predetermined data extraction form.
                There have been marked changes in the literature over the period studied (1950-98), with a recent rise in trials of physical therapy, educational interventions, and complementary treatments. However, overall, most research was either drug (59.1%) or surgically (25.6%) related. Most of the studies reported positive results (94%). Research on oral drugs was significantly more likely to provide a positive result than research on any other intervention (p<0.001 by chi(2) test). Commercially funded studies were significantly more likely to produce a positive result than non-commercially funded research (p=0.0027 by chi(2) test).
                Analysis of time trends indicates that the research agenda does shadow changes in consumer demands. However, there are significant gaps in the research base that need to be considered. Cartilage defects occur in approximately 12% of the population and can result in significant function impairment and reduction in quality of life. Evidence for the variety of surgical treatments available is inconclusive. This study aimed to compare the clinical outcomes of patients with symptomatic cartilage defects treated with matrix-induced autologous chondrocyte implantation (MACI or microfracture (MF). Included patients were >or= 18 and <or= 50 years of age with symptomatic, post-traumatic, single, isolated chondral defects (4-10 cm2) and were randomised to receive MACI or MF. Patients were followed up 8-12, 22-26 and 50-54 weeks post-operatively for efficacy and safety evaluation. Outcome measures were the Tegner, Lysholm and ICRS scores. Sixty patients were included in a randomised study (40 MACI, 20 MF). The difference between baseline and 24 months post-operatively for both treatment groups was significant for the Lysholm, Tegner, patient ICRS and surgeon ICRS scores (all P < 0.0001). However, MACI was significantly more effective over time (24 months versus baseline) than MF according to the Lysholm (P = 0.005), Tegner (P = 0.04), ICRS patient (P = 0.03) and ICRS surgeon (P = 0.02) scores. There were no safety issues related to MACI or MF during the study. MACI is superior to MF in the treatment of articular defects over 2 years. MACI and MF are complementary procedures, depending on the size of the defect and symptom recurrence. The MACI technique represents a significant advance over both first and second generation chondrocyte-based cartilage repair techniques for surgeons, patients, health care institutions and payers in terms of reproducibility, safety, intraoperative time, surgical simplicity and reduced invasiveness.
There is insufficient evidence to draw conclusions on the use of ACI for treating full thickness articular cartilage defects in the knee. Further good quality randomised controlled trials with long-term functional outcomes are required.