The role of viscosupplementation with hylan G-F 20 (Synvisc®) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone

To determine the safety and efficacy of viscosupplementation with hylan G-F 20, a cross-linked hyaluronan preparation, used either alone or in combination with continuous non-steroidal anti-inflammatory drug (NSAID) therapy, a randomized, controlled, multicenter clinical trial, assessed by a blinded assessor, was conducted in 102 patients with osteoarthritis (OA) of the knee. All patients were on continuous NSAID therapy for at least 30 days prior to entering the study. Patients were randomized into three parallel groups: (1) NSAID continuation plus three control arthrocenteses at weekly intervals; (2) NSAID discontinuation but with three weekly intra-articular injections of hylan G-F 20; and (3) NSAID continuation plus three injections, one every week, intra-articular injections of hylan G-F 20. Outcome measures of pain and joint function were evaluated by both the patients and an evaluator at baseline and weeks 1, 2, 3, 7 and 12, with a follow-up telephone evaluation at 26 weeks. At 12 weeks all groups showed statistically significant improvements from baseline, but did not differ from each other. A statistical test for equivalence, the q-statistic, demonstrated that viscosupplementation with hylan G-F 20 was at least as good or better than continuous NSAID therapy for all outcome measurements except activity restriction. At 26 weeks both groups receiving hylan G-F 20 were significantly better than the group receiving NSAIDs alone. A transient local reaction was observed in three patients after hylan G-F 20 injection; only one patient withdrew from the study as a result and all recovered without any sequela.Hylan G-F 20 is a safe and effective treatment for OA of the knee and can be used either as a replacement for or an adjunct to NSAID therapy.     

Clinical experience with the effectiveness and tolerability of hylan G-F 20 in 1047 patients with osteoarthritis of the knee

This retrospective review evaluates the effectiveness and tolerability of hylan G-F 20 for relief of pain due to knee osteoarthritis in a large orthopedic practice over a 5-year period. Prospectively collected data from patients who initiated intra-articular hylan G-F 20 (3 weekly injections) for osteoarthritis knee pain treatment were analyzed. Efficacy variables included physician visual analogue scale (VAS: 100 mm), and patient rating of pain, mobility, and amount of pain medication taken after treatment. Patients (n=1047; 1489 knees) were an average age of 65.3 years, 60% female, and 71% had radiologic osteoarthritis grade IV. Mean VAS scores significantly improved with hylan G-F 20 compared to baseline at all time points (P<.0001). Most knees (62%-89%) responded positively with hylan G-F 20. Pain and mobility improved and less pain medication was needed after therapy. The incidences of local adverse events were 5.2% per patient and 1.2% per injection; most local adverse events were mild or moderate, with severe local events in 0.3% of injections. Our clinical experience shows that hylan G-F 20 effectively relieves osteoarthritis knee pain (as indicated) and reduces pain medication needed for up to 6 months with a low incidence of local adverse events.     

Brace treatment for osteoarthritis of the knee: a prospective randomized multi-centre trial

OBJECTIVE: To evaluate the effect of a brace intended to reduce load in patients with medial or lateral compartmental osteoarthritis (OA) and concurrent varus or valgus alignment, respectively. DESIGN: This multi-centre randomized controlled trial (performed 2001-2003) studies the additive effect of a brace intended to reduce load in conservative treatment of unicompartmental OA of the knee. Setting: Orthopedic department of a university medical centre and of one general hospital. The follow-up was 12 months. Patients: 117 patients with unicompartmental OA of the knee. Intervention group (n=60) comprising conservative treatment with additional brace treatment and a control group (n=57) comprising conservative treatment alone. Primary outcome measures: Pain severity and knee function score. Secondary outcome measures: Walking distance and quality of life. Analysis: Multiple linear regression models according to the intention-to-treat-principle were used to assess outcome differences for the entire group of patients. In addition, we performed explorative subgroup analyses on primary overall outcomes stratified for alignment, degree of OA, origin of OA, and age. RESULTS: Although the primary outcome measures were improved in the intervention group in comparison with the controls at each assessment point, the differences reached only borderline significance. The reported walking distances at 3 months, 12 months and overall were significantly longer in the brace group (P=0.03, P=0.04 and P=0.02, respectively). Subgroup analysis showed a better effect in the varus group, in patients with severe OA, in patients with secondary OA and in patients younger then 60 years. In total 25 patients in the brace group and 14 in the control group changed their initial treatment, mostly (74%) because of a lack of beneficial effect. CONCLUSIONS: The results indicate that a brace intended to reduce load shows small effects in patients with unicompartmental OA. However, many patients do not adhere in the long run to this kind of conservative treatment.     

Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. A prospective,randomized trial

BACKGROUND: Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments. METHODS: One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale. RESULTS: Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system). CONCLUSIONS: No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation.     

The effectiveness of hylan G-F 20 in patients with knee osteoarthritis: an application of two sets of response criteria developed by the OARSI and one set developed by OMERACT-OARSI

OBJECTIVE: Secondary analyses of a previously conducted 1-year randomized controlled trial were performed to assess the application of responder criteria in patients with knee osteoarthritis (OA) using different sets of responder criteria developed by the Osteoarthritis Research Society International (OARSI) (Propositions A and B) for intra-articular drugs and Outcome Measures in Arthritis Clinical Trials (OMERACT)-OARSI (Proposition D). METHODS: Two hundred fifty-five patients with knee OA were randomized to "appropriate care with hylan G-F 20" (AC+H) or "appropriate care without hylan G-F 20" (AC). A patient was defined as a responder at month 12 based on change in Western Ontario and McMaster Universities Osteoarthritis Index pain and function (0-100 normalized scale) and patient global assessment of OA in the study knee (at least one-category improvement in very poor, poor, fair, good and very good). All propositions incorporate both minimum relative and absolute changes. RESULTS: Results demonstrated that statistically significant differences in responders between treatment groups, in favor of hylan G-F 20, were detected for Proposition A (AC+H=53.5%, AC=25.2%), Proposition B (AC+H=56.7%, AC=32.3%) and Proposition D (AC+H=66.9%, AC=42.5%). The highest effectiveness in both treatment groups was observed with Proposition D, whereas Proposition A resulted in the lowest effectiveness in both treatment groups. The treatment group differences always exceeded the required 20% minimum clinically important difference between groups established a priori, and were 28.3%, 24.4% and 24.4% for Propositions A, B and D, respectively. CONCLUSION: This analysis provides evidence for the capacity of OARSI and OMERACT-OARSI responder criteria to detect clinically important statistically detectable differences between treatment groups.     

Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein

OBJECTIVE: To evaluate the efficacy and safety of Harpagophytum in the treatment of hip and knee osteoarthritis comparatively with the slow-acting drug for osteoarthritis, diacerhein. PATIENTS AND METHODS: A multicenter, randomized, double-blind, parallel-group study was conducted in 122 patients with hip and/or knee osteoarthritis. Treatment duration was four months and the primary evaluation criterion was the pain score on a visual analog scale. Harpagophytum 2,610 mg per day was compared with diacerhein 100 mg per day. RESULTS: After four months, considerable improvements in osteoarthritis symptoms were seen in both groups, with no significant differences for pain, functional disability, or the Lequesne score. However, use of analgesic (acetaminophen-caffeine) and nonsteroidal anti-inflammatory (diclofenac) medications was significantly reduced in the Harpagophytum group, which also had a significantly lower rate of adverse events. CONCLUSION: In this study, Harpagophytum was at least as effective as a reference drug (diacerhein) in the treatment of knee or hip osteoarthritis and reduced the need for analgesic and nonsteroidal anti-inflammatory therapy.     

High-intensity versus low-level laser therapy in the treatment of patients with knee osteoarthritis: a randomized controlled trial

The aim of this randomized controlled study was to compare the effects of low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) on pain relief and functional improvement in patients with knee osteoarthritis (KOA). A total of 53 male patients participated in this study, with a mean (SD) age of 54.6 (8.49) years. Patients were randomly assigned into three groups and treated with HILT and exercise (HILT?+?EX), LLLT and exercise (LLLT?+?EX), and placebo laser plus exercise (PL?+?EX) in groups 1, 2, and 3, respectively. The outcomes measured were pain level measured by visual analog scale (VAS) and knee function measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Statistical analyses were performed to compare the differences between baseline and posttreatment measurements. The level of statistical significance was set as P?<?0.05. The result showed that HILT and LLLT combined with exercise were effective treatment modalities in decreasing the VAS and WOMAC scores after 6 weeks of treatment. HILT combined with exercises was more effective than LLLT combined with exercises, and both treatment modalities were better than exercises alone in the treatment of patients with KOA.     

Prospective, multi-centre, randomised evaluation of the safety and efficacy of five dosing regimens of viscosupplementation with hylan G-F 20 in patients with symptomatic tibio-femoral osteoarthritis: a pilot study

Introduction  Viscosupplementation by repeated intra-articular injections of hyaluronic acid (HA) is used widely in the treatment of symptomatic knee osteoarthritis (OA). The number of injections required can limit the availability of treatment and affect patient compliance. The aim of this study was to assess different dosing regimens of hylan G-F 20, a high molecular-weight cross-linked derivative of HA, in the treatment of pain due to knee OA. Materials and methods  Pilot, prospective, multi-centre, open-label, randomised trial in 100 patients with unilateral, symptomatic, tibio-femoral OA (Kellgren–Lawrence grade II or III), aged ≥40 years. Patients were randomised to receive varying dosing regimens of hylan G-F 20 (1 × 6 mL, 1 × 4 mL, 2 × 4 mL 2 weeks apart, 3 × 4 mL 1 week apart, or 3 × 2 mL 1 week apart). Adverse events (AE’s) were monitored throughout the study. The primary efficacy endpoint was the change from baseline in the patient-rated knee OA pain assessment (100 mm visual analogue scale (VAS)) at 24 weeks. The secondary efficacy criteria included the WOMAC index, patient and physician global assessments using a 100 mm VAS, and knee OA pain assessment at all other visits. Concomitant use of permitted rescue medications (paracetamol) was also assessed. Results  The treatment was well tolerated overall. Patients in the 3 × 4 mL group reported the highest percentage of device-related local AE’s (30%) while patients in the 1 × 6 mL and 3 × 2 mL groups reported only 10%. There were no serious device-related AEs. There was a statistically significant improvement from baseline at week 24 in all efficacy endpoints for all treatment regimens. The 1 × 6 and 3 × 4 and 3 × 2 mL treatment groups showed the greatest mean improvements (−34.9, −32.6 and −36.7 mm respectively) in the patient-rated knee OA pain assessment VAS. Conclusion  This study suggests that a single 6 mL injection of hylan G-F 20 may be as efficacious, and as well tolerated, as 3 × 2 mL one week apart. A double-blind, controlled trial is needed to confirm these data.     

Efficacy of pulsed Nd:YAG laser in the treatment of patients with knee osteoarthritis: a randomized controlled trial

The purpose of this study was to investigate the effects of pulsed Nd:YAG laser plus glucosamine/chondroitin sulfate (GCS) in patients with knee osteoarthritis (KOA) by examining changes in pain and knee function, as well as synovial thickness (ST) and femoral cartilage thickness (FCT). Sixty-seven male patients participated, with a mean (SD) age of 53.85 (4.39) years, weight of 84.01 (4.70) kg, height of 171.51 (3.96) cm, and BMI of 28.56 (1.22). Group 1 was treated with high-intensity laser therapy (HILT), GCS, and exercises (HILT?+?GCS?+?EX). Group 2 was treated with GCS plus exercises (GCS?+?EX), and group 3 received placebo laser plus exercises (PL?+?EX). The outcomes measured were pain level and functional disability using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. ST and FCT were measured by ultrasound examination. Statistical analyses were performed to compare differences between baseline and after 6 weeks of treatment and then after 3 months of follow-up. Statistical significance was set at p?<?0.05. VAS and WOMAC were significantly decreased in all groups after 6 weeks, with nonsignificant differences between 6 weeks and 3 months of follow-up. ST was significantly decreased in the HILT?+?GCS?+?EX group posttreatment, with nonsignificant decreases in the GCS?+?EX and PL?+?EX groups, as well as nonsignificant differences to FCT in all groups. Overall, pulsed Nd:YAG laser combined with GCS and exercises was more effective than GCS?+?EX and exercises alone in the treatment of KOA patients.     

Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial

We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis (OA) of the knee. This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy. In this study, 142 female patients with moderate OA of the knee, who had been recommended to undergo home exercise at the first visit to the hospital, were randomly given glucosamine hydrochloride, risedronate, or no additive. Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee, no significant differences were observed between the groups regarding any of the scales, indicating no significant additive effect of glucosamine or risedronate. One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee. This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee, the effect would not be greater than the effect of knee exercise to improve the symptoms.     

Minimal invasive and computer-assisted total knee replacement compared with the minimal invasive technique: a prospective, randomized trial with short-term outcomes

Introduction

Up to now, no prospective, randomized comparisons between minimal invasive and computer-assisted total knee arthroplasty (MICA-TKA), and minimal invasive technique (MI-TKA) has been documented to evaluate not only clinical, but also radiologic results of the MICA-TKA. This prospective, randomized study was performed to compare the short-term results of MICA-TKA with minimal invasive technique MI-TKA for 6-month follow-up.

Patients and methods

We reported the clinical and radiological results of 80 subjects who had cruciate-substituting, TKA-implanted primary total knee arthroplasties using either minimal invasive and computer-assisted technique (40 patients Group I) or minimal invasive technique (40 patients, Group II). Tourniquet time, length of skin incision, and total blood loss were compared. Knee society scores (KSSs), knee society functional scores (KSFSs), range of motion (ROM), and radiographic results were assessed and reported preoperatively and at 6-month follow-up.

Results

The accuracy of the implantations in relation to the coronal mechanical axis in Group I was superior to that of Group II (P < 0.05). The femoral rotational profile revealed the prosthesis in Group I that was implanted with significantly less internal rotation than in Group II. The average blood loss in patients of Group I was significantly reduced as compared to patients of Group II. No significant difference was detected in terms of tourniquet time or length of skin incision. Clinical results, with regard to ROMs and KSSs, as well as KSFSs were equally good in both the groups.

Conclusions

Better alignment and similarity of good clinical results at short-term follow-up may provide subjects who receive MICA-TKA with long-term endurance of their implants. Further studies on longer-term outcomes and functional improvements are required to validate these possibilities.