A prospective randomised controlled clinical trial comparing the efficacy of different molecular weight hyaluronan solutions in the treatment of knee osteoarthritis

Viscosupplementation consists of injecting exagenous hyaluronan (HA) into the synovial joints to restore the normal rheological environment which deteriorates severely in osteoarthritic (OA) joints. Efficacy might be related to the rheological properties and molecular weight (MW) of the hyaluronan preparations. This prospective, controlled, double-blind, randomised clinical trial was aimed at comparing the elastoviscous properties of a high molecular weight viscosupplement, hylan G-F 20, with that of a lower molecular weight hyaluronan product in order to determine the relationship of elastoviscosity to efficacy, alongside placebo, in the treatment of patients with knee OA. The results were analysed as a completers analysis with 59 patients. Primary outcome measures included the Western Ontario and Mc Master Universities Osteoarthritis Index (WOMAC) for pain, stiffness and function scores, and patient and physician global assessments (0–100 scale). For patient (PGA) and physician global assessments (PhGA), the 0–100 scale was used, with 100 being the worst. Follow-up assessments were made at intervals of 1, 3 and 6 months after the first injection. Local adverse events, such as transient pain at the injection site or warm knee lasting for one night, were recorded in two patients (3%). In all groups, the WOMAC pain score exhibited a significant difference from the baseline value; neither treatment group was significantly different from the placebo group, but total pain score was significantly better than baseline for both of the HA groups at the end of 6 months (p < 0.05). Improvement in WOMAC physical function score favoured both sodium hyaluronate and hylan G-F 20 after the first month, and remained significant until the end of 6 months (p < 0.01). In the placebo group, the physical function scores became worse after the end of the 1st month; the scores at the end of 6 months were no different from those at the beginning. The WOMAC stiffness scores of both of the hyaluronic acid groups improved with the first injection, and remained significantly better than the placebo group until the end of the survey (p < 0.001). All groups expressed improvement with PGA scores after the first injection. At the end of 6 months all three groups were similar, but the treatment groups were significantly better than the placebo group (p < 0.05), and all were significantly better than at the beginning (p < 0.05). The PhGA scores were similar in all groups until after the third injection. The second group was slightly better in the controls at 1 and 3 months, but all the groups were similar at the end of 6 months. Although the placebo group seemed worse, it was not statistically significant. Compared with lower molecular weight HA, the higher molecular weight HA might be more efficacious in treating knee OA, but heterogeneity of previous studies limited definitive conclusions. Patients treated by injection of either of two hyaluronan preparations showed clinical improvement for pain, though no different from the placebo group; WOMAC stiffness scores were better than placebo in the HA groups, whereas PGA scores showed improvement in all groups but HA groups were better than placebo. PhGA scores were worse in the placebo group, but not to a statistically-significant extent. The HA groups did not differ in terms of clinical efficacy.     

Combining two hyaluronic acids in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial

Synovial fluid in patients may differ in molecular weight depending on the presence and degree of osteoarthritis. Treatment is not directed at this relationship. Patients with osteoarthritis of the knee with resting visual analogue scale (VAS) pain of >45 mm were included in a randomized, prospective, double-blind cohort followed for 16 weeks. Patients were randomized at baseline to receive a three intra-articular injection series with one of: dual molecular weight (DMW; 580-780 kDa + 1.2 to 2.0 million Da); low molecular weight (LMW; 500-730 kDa); high molecular weight (HMW; 6 million Da); or saline placebo over 3 weeks. Patients completed baseline assessment of rest and walking VAS pain (primary efficacy variable), collection of a 5-point categorical global satisfaction score, and record of adverse events. Two-hundred and twenty-five patients (age 68 +/- 8 y) were screened and 200 were randomized to one of the four groups. There were no differences at baseline between groups. At 4, 12 and 16 weeks, respectively, walking VAS pain was significantly improved in all treatment groups vs. placebo: DMW (79.6%, p < 0.001; 85.6, p < 0.001; 89.3%, p < 0.001); LMW (73.6%, p < 0.001; 76.4, p < 0.001; 81.3%, p < 0.001) and HMW (69.1%, p < 0.001; 81.0, p < 0.001; 79.1%, p < 0.001). Patients in the DMW group had significantly greater improvement (p < 0.007) in VAS walking pain by 3 weeks (following the second injection) compared to all groups. This difference was persistent at 16 weeks. Greater improvement in patients who received the DMW product was achieved by the second injection persistent at 16 weeks.     

Why we should definitely include intra-articular hyaluronic acid as a therapeutic option in the management of knee osteoarthritis: Results of an extensive critical literature review

Objectives

There is a discrepancy between evidence in support of the widespread use of intra-articular hyaluronic acid (IAHA) to treat knee osteoarthritis (OA) in clinical practice, and the often discordant recommendations from multiple international guideline committees, which requires further investigation.

Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle. A prospective randomized trial with long-term follow-up

OBJECTIVE: The goal of this study has been to determine whether hyaluronic acid (HA) or exercise therapy can improve functional parameters in patients with osteoarthritis (OA) of the ankle. METHODS: In a prospective clinical trial, 43 ankles (30 patients) with radiographic Kellgren Lawrence grade III OA were randomized to receive three intra-articular HA injections, with one-week interval of or exercise therapy for six weeks. Patients were evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and followed-up after 12 months. RESULTS: Total AOFAS Ankle-Hindfoot score of OA patients has improved in both groups, varying from 61.6+/-16.8 to 90.1+/-9.7 with HA treatment and from 72.1+/-16.6 to 87.5+/-17.5 using exercise therapy at the end of the trial (p<0.01). There were no statistically significant differences between the groups. CONCLUSION: This prospective randomized trial confirmed that, both HA injections and exercise therapy provide functional improvement. However, larger trials with longer follow-up are necessary for more definite conclusions.     

Effects of different hyaluronic acid products on synovial fluid NO levels in knee osteoarthritis

The aim of the present study was to evaluate the effects of different hyaluronic acid forms on synovial fluid nitric oxide (NO) levels and glutathione peroxidase (GSHPx) activities in the treatment of patients with knee osteoarthritis (OA). Forty patients were equally randomized into two groups and treated with native sodium hyaluronate (group I) or with cross-linked hylan G-F 20 (group II). Clinical evaluations and synovial fluid aspirations were performed before the first (baseline), the second (week 1), and third injections (week 2), and a week after the third injection (week 3). NO levels were reduced at the end of the study in both groups (p<0.01 in group I, p=0.001 in group II), while no significant change was found in GSHPx activity. Also, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores and WOMAC physical function scores were gradually improved at all follow-ups in the two groups. No significant differences between the two groups of NO levels, GSHPx activity, WOMAC pain scores, WOMAC stiffness scores, and WOMAC physical function scores were recorded during the study. Intra-articular hyaluronic acid therapy may reduce synovial fluid NO levels. These effects do not seem to be dependent on the molecular weight and various structural changes of hyaluronan products.     

Hylan G-F 20 efficacy on articular cartilage quality in patients with knee osteoarthritis: clinical and MRI assessment

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.     

Effectiveness of home exercise on pain and disability from osteoarthritis of the knee: a randomised controlled trial

OBJECTIVE: To assess the effect of a home based exercise programme, designed to improve quadriceps strength, on knee pain and disability. METHODS: 191 men and women with knee pain aged 40-80 were recruited from the community and randomised to exercise (n = 113) or no intervention (n = 78). The exercise group performed strengthening exercises daily for six months. The primary outcome measure was change in knee pain (Western Ontario McMaster Osteoarthritis index (WOMAC)). Secondary measures included visual analogue scales (VAS) for pain on stairs and walking and WOMAC physical function scores. RESULTS: WOMAC pain score reduced by 22.5% in the exercise group and by 6.2% in the control group (between group difference p < 0.05, unpaired t test). VAS scores for pain also reduced in the exercise group compared with the control group (p < 0.05). Physical function scores reduced by 17.4% in the exercise group and were unchanged in controls (p < 0.05). CONCLUSION: A simple programme of home quadriceps exercises can significantly improve self reported knee pain and function.     

悬吊技术联合Mulligan手法对膝骨关节炎老年人群运动后疼痛的康复效果

目的 探究悬吊技术联合Mulligan手法用于膝骨关节炎老年人运动后膝关节疼痛康复的效果.方法 选取84例单侧膝关节运动后疼痛的膝骨关节炎老年患者,依据随机数字表法分为观察组和对照组,各42例.对照组给予常规物理治疗与悬吊训练治疗,观察组在对照组基础上给予Mulligan技术治疗.比较两组治疗开始前与治疗后视觉模拟评分(VAS)疼痛评分、QOL-BREF评分、LEFS下肢功能评分、膝关节功能评分、关节活动度、四头肌与腘绳肌肌力.结果 两组治疗后VAS评分明显降低(P<0.05),且观察组VAS评分明显低于对照组(P<0.05).两组治疗后QOL-BREF评分/LEFS评分、膝关节功能评分、关节活动度、四头肌与腘绳肌肌力较治疗前明显提高(P<0.05),且治疗后观察组QOL-BREF评分/LEFS评分、膝关节功能评分、关节活动度、四头肌与腘绳肌肌力明显高于对照组(P<0.05).结论 对于膝关节运动后疼痛的膝骨关节炎老年患者,悬吊技术联合Mulligan手法,能有效缓解膝关节疼痛、促进膝关节功能恢复,提高患者生活质量.     

Efficacy of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis

 To assess the efficacy of intra-articular hyaluronic acid in patients with knee osteoarthritis, sixty female patients with knee osteoarthritis were randomised to three weekly intra-articular injections of 30 mg sodium hyaluronate (Na HA) with a high molecular weight (1.0 to 2.9 million Da) or 40 mg 6-methylprednisolone acetate (6-MPA). The clinical assessments included pain at rest, at weight-bearing and on walking, Lequesne Index and active range of knee flexion. Assessments were done at baseline, at week 4, and at months 3 and 6. A significant decrease in VAS scores for pain at rest, at weight-bearing and pain on walking, and in Lequesne index was found in both groups at week 4 when compared to baseline and there was no significant differences between the two groups. However, at 3^rd month improvement in all pain scores and Lequesne index was found in favour of hyaluronic acid. At 6^th, no significant difference was found between the treatment groups. Improvement in pain was accompanied by an increase in joint flexion at week 4 and at month 3 in both groups. Both treatments were well-tolerated. The results showed that both intra-articular hyaluronic acid and 6-MPA treatments provide clinically significant improvement and demonstrated that Na HA has a long-term beneficial effect in patients with knee osteoarthritis. Received: 13 May 2002 / Accepted: 21 November 2002     

Therapeutic effect of spa therapy and short wave therapy in knee osteoarthritis: a randomized,single blind,controlled trial

Spa therapy and short wave therapy are two of the most commonly used non-pharmacological approaches for osteoarthritis. The aim of this study was to assess their efficacy in comparison to conventional therapy in patients with osteoarthritis of the knee in a single blind, randomized, controlled trial. Seventy-four outpatients were enrolled; 30 patients were treated with a combination of daily local mud packs and arsenical ferruginous mineral bath water from the thermal resort of Levico Terme (Trento, Italy) for 3 weeks; 24 patients were treated with short wave therapy for the same period and 20 patients continued regular, routine ambulatory care. Patients were assessed at baseline, upon completion of the 3-week treatment period, and 12 weeks later. Spa therapy and short wave therapy both demonstrated effective symptomatic treatment in osteoarthritis of the knee at the end of the treatment, but only the spa therapy was shown to have efficacy persistent over time. Our study demonstrated the superiority of arsenical ferruginous spa therapy compared to short wave therapy in the treatment of osteoarthritis of the knee, probably in relationship to the specific effects of the minerals in this water.     

A randomized study protocol comparing the platelet-rich plasma with hyaluronic acid in the treatment of symptomatic knee osteoarthritis

Background:In recent years, intra articular injection of platelet rich plasma has attracted increasing attention. The major aim of our current randomized controlled double-blind study was to compare long-term outcomes of intra-articular injection of hyaluronic acid or platelet rich plasma in the treatment of the patients with knee osteoarthritis.Methods:This is a kind of double-blind, randomized, prospective, and comparative clinical investigation with the allocation ratio of 1:1 and was approved by our institutional review Committee. Between 2020 and 2021, altogether 2 hundred patients will be selected to participate in our present study. We will report the randomized experiments in accordance with the guidelines of Consolidated Standards of Reporting Trials and then offer the Consolidated Standards of Reporting Trials flow chart. The inclusion criteria were: patients aged from 40 to 70 years old, patients with chief complaint history of at least 1 month and knee joint pain for nearly 6 months, need the analgesic drug treatment, and radiology confirmed knee osteoarthritis. The eligible patients would be randomly divided into 2 groups through applying the random numbers generated by computer before surgery. Outcomes after treatment were assessed using the Western Ontario and McMaster University and the scoring systems of visual analogue scale which were recorded through questionnaires accomplished via the patients prior to the first injection and then at three and six months, 1 and 2 years follow-up. Any adverse events occurred within 1 year after surgery were recorded during follow-up.Results:This should suggest whether biological methods can offer more lasting outcomes than the viscosification.Trial registration:This study protocol was registered in Research Registry (researchregistry6265).     

Efficacy and safety of thread embedding acupuncture for knee osteoarthritis: A randomized controlled pilot trial

Background:Thread embedding acupuncture (TEA) is a widely used clinical procedure for the treatment of musculoskeletal pain. However, few clinical studies have been conducted on the efficacy and safety of TEA for knee osteoarthritis (KOA), and data from randomized controlled trials are lacking. This randomized controlled pilot study aimed to assess the feasibility of conducting large-scale studies on the efficacy and safety of TEA for KOA.Methods:Forty participants were included in the study and randomly divided into 2 groups (TEA and acupuncture) of 20 each. The intervention period was 6 weeks. The experimental group received TEA once a week (total of 6 sessions) on 14 defined knee areas, and the control group received acupuncture twice a week (total of 12 sessions) on 9 defined acupuncture points. The primary outcome measure was the visual analogue scale score, and the secondary outcome measures were the short-form McGill pain questionnaire, and Western Ontario and McMaster Universities Osteoarthritis Index scores. Participants were assessed prior to the intervention (baseline) and at 3, 6, and 10 weeks (4 weeks after the end of intervention). The adverse effects of TEA and acupuncture were documented. Hematological examination and biochemical tests were performed at the screening and at 6 weeks.Results:Of the 40 participants, 37 completed the study and 3 participants dropped out. Both the TEA and acupuncture groups showed a significant improvement in the visual analogue scale, short-form McGill Pain Questionnaire, and Western Ontario and McMaster Universities Osteoarthritis Index scores in a time-dependent manner. However, there was no significant interaction between group and time. No serious adverse events were reported in the groups, and no clinically significant changes were observed in the hematological and biochemical parameters.Conclusion:This pilot study suggests that TEA is a safe and effective procedure for relieving pain in patients with KOA. The results of this study provide basic data and indicate the feasibility of large-scale clinical studies to evaluate the efficacy and safety of TEA for KOA.     

Knee vs hip single-joint intra-articular hyaluronic acid injection in patients with both hip and knee osteoarthritis: a pilot study

This paper aims to compare the results of single-joint knee vs hip hyaluronic acid (HA) injections in patients with osteoarthritis (OA) involving both the knee and hip joints. Thirty-eight patients who were diagnosed to have both hip and knee OA were enrolled. Patients were divided into two groups to receive HA injection three times at 1-week intervals either to the hip or knee joints. Pain level during activities and rest was measured by using visual analog scale (VAS). Western Ontario and McMaster University Osteoarthritis Index (WOMAC 5-point Likert 3.0) was also used prior to the injections and 1 month after the 3rd injection. In the knee injection group, the intragroup analysis revealed significant improvements in VAS activity pain, VAS rest pain, and WOMAC pain values following injection when compared with preinjection values, while no significant difference was detected in WOMAC stiffness, WOMAC physical function, and WOMAC total values. In the hip injection group, VAS activity pain, VAS rest pain, WOMAC pain, WOMAC stiffness, WOMAC physical function, and WOMAC total values showed significant improvement after the injection when compared with preinjection values. Although statistically not significant (p > 0.05), the comparison of the differences (preinjection–postinjection) between the groups demonstrated higher values in the hip injection group. We imply that intra-articular single-joint HA injections either to the knee or hip joints in OA patients with involvement of both of these joints are effective with regard to pain and functional status.     

Efficacy and safety of Biqi capsule in the treatment of knee osteoarthritis: A protocol of a randomized controlled trial

Background:Knee osteoarthritis (KOA) is a chronic and degenerative bone and joint disease, with KOA, cartilage degeneration, destruction and subchondral bone remodeling as the main pathological features. Its clinical symptoms are knee pain, swelling, limited activity, and long course of disease can cause joint deformities. At present, the early treatment of Western medicine is mainly the use of nonsteroidal drugs for anti-inflammation and removing pain, but because the efficacy of these drugs is unstable, the disease is easy to repeat after treatment, and the clinical effect is not good. Although Biqi capsule has advantages in the treatment of KOA, there is a lack of standard clinical studies to verify it, so the purpose of this randomized controlled study is to evaluate the efficacy and safety of Biqi capsule in the treatment of KOA.Methods:This is a prospective randomized controlled trial to study the efficacy and safety of Biqi capsule in the treatment of KOA. The patients were randomly divided into a treatment group and a control group according to 1:1. Among them, treatment group: Biqi capsule combined with diclofenac sodium sustained release tablets; Control group: Diclofenac sodium sustained-release tablets alone. Both groups were treated with standard treatment for 2 weeks and were followed up for 30 days to pay attention to the efficacy and safety indexes. Observation indicators included: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Hospital for Special Surgery Knee Score (HSS), liver and kidney function, adverse reactions, and so on. SPSS 25.0 software is used for data analysis.Discussion:This study will evaluate the efficacy and safety of Biqi capsule in the treatment of KOA, and the results of this experiment will provide a clinical basis for Biqi capsule in the treatment of KOA.Trial registration:OSF Registration number: DOI 10.17605/OSF.IO/6HB9D     

A randomized controlled trial to evaluate the slow‐acting symptom‐modifying effects of colchicine in osteoarthritis of the knee: A preliminary report

Objective

To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.

Methods

Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double‐blind, placebo‐controlled trial over a 5‐month period.

Results

The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel‐Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T² test (P = 0.0115).

Conclusion

Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

     

The effect of isokinetic and aerobic exercises on serum interleukin-6 and tumor necrosis factor alpha levels,pain, and functional activity in patients with knee osteoarthritis

Objectives. The aim of this study is to investigate the effects of isokinetic and aerobic exercise training programs on serum pro-inflammatory cytokine levels, pain, and functional activity in patients with knee osteoarthritis (OA).

Methods. Forty-two postmenopausal women and men with knee OA according to American College of Rheumatology diagnostic criteria were included. Patients were randomized into isokinetic and aerobic exercises and control groups. In intervention groups, patients were included in predetermined exercise programs 3 times per week for 6 weeks. Severity of pain, functional activity status, muscle strength, functional capacity, and serum cytokine levels were evaluated at baseline and at the 6th week.

Results. At the end of 6th week, there was no statistically significant decrease in serum pro-inflammatory cytokine levels in both the exercise groups, although C-reactive protein levels exhibited a strong trend toward significance. We found a significant decrease in visual analog scale and Western Ontario McMaster Osteoarthritis Index scores, and significant increase in functional capacity and muscle strength in both the exercise groups compared with those in the control group.