The Efficacy and Safety of Chinese Herbal Medicine in the Treatment of Knee Osteoarthritis: An Updated Systematic Review and Meta-Analysis of 56 Randomized Controlled Trials

Objective. This systematic review and meta-analysis were performed to investigate the efficacy and safety of Chinese herbal medicine (CHM) in the treatment of knee osteoarthritis (KOA). Methods. An electronic search was conducted in eight databases (PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese VIP Database, and Wanfang Database) from inception until December 2019. The risk of bias assessment of the included RCTs was evaluated by Cochrane collaboration’s tool. The inclusion criteria were RCTs that investigated the efficacy and safety of CHM in the treatment of KOA, with no restrictions on publication status or language. The exclusion criteria included nonrandomized or quasi-RCTs, no clear KOA diagnostic approach, combined Chinese medicinal herbs with other traditional Chinese medicine treatment modalities, and published using repeated data and missing data. We computed the relative risk (RR) and the standard mean difference (SMD) for dichotomous outcomes and continuous outcomes, respectively. When heterogeneity was detected or there was significant statistical heterogeneity ( P < 0.05 or I 2 > 50 % ), a random-effects model was employed, followed by further subgroup analysis and metaregression estimations to ascertain the origins of heterogeneity. Otherwise, we used a fixed-effects model ( P ≥ 0.05 or I 2 ≤ 50 % ). The primary outcome measures were visual analog score (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, and Lequesne index. Secondary outcome measures were the total clinical effective rate and adverse events. The meta-analysis was performed using the Stata 14.0 software. Results. A total of 56 RCTs comprising 5350 patients met the inclusion criteria. This meta-analysis showed that application of CHM as adjuvant therapy or monotherapy for KOA can significantly decrease VAS, WOMAC, and the Lequesne index and improve the Lysholm score as well as the total effective rate. In addition, this treatment has fewer adverse effects, suggesting that CHM is generally safe and well tolerated among patients with KOA. Conclusion. Our study offers supportive evidence that CHM, either adjuvant therapy or monotherapy, reduces the VAS, WOMAC, and Lequesne index and improves the Lysholm score and overall effective rate in patients with KOA. Additionally, CHM was well tolerated and safe in KOA patients. We found frequently used CHMs that might contribute to the formulation of a herbal formula that could be considered for further clinical use. However, given the heterogeneity and limited sample size in this study, larger multicenter and high-quality RCTs are needed to validate the benefits of CHM in the treatment of KOA.

Results of use of polyacrylamide gel Noltrexsin in patients with different grades of gonarthrosis in outpatient practice

Introduction. Osteoarthritis of the knee joints is the most common joint disease affecting more than 80% of people over 55 years of age. The priority method for the treatment of gonarthrosis is the use of local injection therapy with the introduction of synovial fluid endoprostheses based on hyaluronic acid, included in the Second Step of the ESCEO 2019 algorithm. Viscoelastic polyacrylamide gels for intra-articular administration since 2003 have also shown their high effciency in the symptomatic OA treatment. Since 2018, the new 3rd generation PAAG endoprosthesis of synovial fluid, Noltrexsin, has been actively used.Objective. To compare the efficacy and safety of Noltrexsin viscoprosthesis use with oral NSAIDs in patients with grade I-III of gonarthrosis.Materials and methods. 40 patients with gonarthrosis participated in a comparative study of the effcacy and safety of injection therapy Noltrexsin 4.0 ml No. 2 (study group, А) and oral administration of NSAIDs 200 mg per day (comparison group, В). NSAIDs were taken in groups A and B, the duration of therapy in both groups was 1 month. The results were evaluated by standard examination methods, including measuring the range of motion in the joint and scoring of physical signs, tests with walking up the stairs and at a distance, VAS, WOMAC, Lequesne Index.Results. In group А, a more signifcant reduction in pain according to VAS was revealed to 15–20 mm at the grade I–II of gonarthrosis and up to 25–30 mm in the grade III, a decrease in the Lequesne index to 1–2 and 3–4 points, respectively. In group В with a standard therapy, and then on-demand within 6 months, a decrease in VAS was revealed on the 8–9th day, and after 6 months the level of pain at the grade I–II did not exceed 20–25 mm, at the grade 3 it did not decrease below 40–45 mm. The Lequesne Index decreased to 2 points at the grade I–II and to 6–7 points at the grade III. Changes of WOMAC index correlated with VAS.Conclusions. 1. Noltrexsin can be used as a safe endoprosthesis of synovial fluid in the form of local injection therapy in patients with insufficient effect of chondroprotectors and NSAIDs. 2. Noltrexsin is recommended for use at all stages of arthrosis, as well as in comorbid patients.

Associated factors with the severity of hip involvement in spondyloarthritis and efficacy of TNF α inhibitors in these patients

Introduction: Hip involvement in patients with spondyloarthritis is responsible for disability and functional impairment. Its treatment is not codified. Our study aimed to determine the associated factors with moderate and severe hip involvement in spondyloarthritis patients. It also aimed to assess the efficacy of tumour necrosis factor inhibitors (TNFi) on hip disease. Methods: We conducted a cross-sectional study, including 44 spondyloarthritis patients with hip involvement. Hip involvement was diagnosed based on radiographic findings. We assessed the following parameters: Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Radiology Index (BASRI), patient global assessment (PGA), and Lequesne index. We compared these parameters and the mean radiographic joint space width between the time of the study to those right before the use of TNFi. Results: Hip involvement was bilateral in 31 patients. The mean age was 44.56±12.21 years. There were 29 men. Severe and moderate involvement (BASRI-hip>3) was reported in 21 hips from 75 affected. These patients were older and had longer diagnosis delay than patients with BASRI-hip<3. They had a higher body mass index and more limited spine mobility (BASMI). Functional hip impairment assessed by the Lequesne index was higher in these patients. TNFi prescribed in 23 patients with hip involvement, led to an improvement in the Lequesne index (12.75vs7.5,p:0.001) and PGA (7vs2,p:0.001). However, the mean joint space width remained unchanged (3.8vs3.7mm,p:0.532). Conclusion : Our study showed that higher body mass and Lequesne indexes are associated with moderate and severe hip involvement. TNFi may improve both the Lequesne index and PGA and stabilize the radiological findings.

Clinical Manifestations, Histopathological Changes And Quality Of Life In Patients With Advanced Knee Osteoarthritis Caused By Age, Trauma, Obesity And Their Combination

Objective — to reveal and analyze clinical characteristics, knee joint histopathology, and quality of life in patients at late stages of knee osteoarthritis (OA) triggered by age, trauma, metabolic syndrome, or their combination. Material and methods — We studied 120 subjects with knee OA (sensu Altman R.D., 1991) of Kellgren-Lawrence Grades 3-4. They were distributed among 4 groups (30 participants in each) based on the presence of age-related, post-traumatic, metabolic, or combined phenotypes. Clinical examination of patients with pain and their functional status evaluation (via Visual Analogue Scale, WOMAC, Lequesne index), quality of life assessment (MOS SF-36 questionnaire), along with histopathological study of medial tibial plateau cartilage and synovial membrane, were caried out, followed by statistical data processing. Results — Age-related OA phenotype was characterized by the latest clinical onset [59.5 (54-68) years of age] with the largest average patient age [72.5 (63-77) years], moderate to severe pain and knee dysfunction [total WOMAC score of 160 (127-190) points and Lequesne index of 20 (8-21) points], severe degenerative cartilage lesions [8.5 (6-10) points sensu Mankin] with high-grade synovitis [5 (3-8) points sensu Krenn]. Post-traumatic OA phenotype was distinguished by the lowest pain, stiffness and knee functional limitations [total WOMAC score of 129 (100-166), Lequesne index of 15 (14-19)], the highest quality of life in patients [physical component summary of 34.1 (30.5-36.1) points, mental component summary of 40.4 (32.9-43.8) points] against the background of local severe cartilage lesions [8 (6-8) sensu Mankin] with reparative pattern and synovial fibrosis. For metabolic OA phenotype, the typical traits included female-biased sex ratio (87%), high prevalence of clinical synovitis (77%), severe pain and functional knee disorders [total WOMAC score of 188 (162-207) points, Lequesne index of 20 (19-23) points], the worst quality of life [physical component summary of 28.0 (24.3-31.9) points, mental component summary of 30.9 (26.9-35.9) points], vascular invasion of cartilage, and high-grade synovitis [4 (3-5) points sensu Krenn]. Combined OA phenotype was characterized by variable clinical and histopathological features. Conclusion — Comprehensive comparative clinical and morphological analysis of late-stage knee OA of various origin was completed, and age-related, post-traumatic, metabolic and combined OA phenotypes were studied. The methodological basis for differential approach to treating different categories of OA patients was developed.

Sports Participation, Demographic Factors and Knee Symptom Severity in Riyadh, Saudi Arabia

Aims: to explore the prevalence of knee symptoms in the general population of Riyadh, Saudi Arabia, and evaluate the impact of sports participation and other demographic variables on the progression of knee symptoms in Riyadh, Saudi Arabia. Study design: Cross-sectional study Place and duration of study: A self-administered online survey was conducted in Riyadh, Saudi Arabia between September 2020 to March 2021. Methodology: A total of 589 participants age 18 or older who reported concerns of knee symptoms and provided written informed consent were enrolled in the study. We excluded respondents who had undergone knee surgery (n = 16) and those diagnosed with rheumatoid arthritis or other types of arthritis (n = 25). We collected demographic information (eg, age, gender, types of engaged sports, sports participation hours, and frequency of participation per week) and knee symptoms and severity using the Lequesne index tool. Results: Advanced age was significantly associated with a higher severity score (P < .001). We found a statistically significant association between body mass index and knee symptom severity. We noted no severe knee symptoms in participants engaging in weightlifting. Most participants (64.7%) reported that walking was their most frequent exercise, and knee symptoms were common. Of respondents who walk as their primary sport, 10.6% of them are considered disabled with a severe form of knee pain according to the Lequesne index (which uses the term “handicapped” rather than disabled). Conclusion: Older and overweight respondents had a high prevalence of knee symptoms. Interestingly, the prevalence rates of individuals without knee symptoms did not differ regarding sport participation. Sports participation frequency did not change the prevalence or severity of knee symptoms, while longer exercise duration was associated with lower knee symptom severity rates.

Molecular Weight of Hyaluronic Acid Has Major Influence on Its Efficacy and Safety for Viscosupplementation in Hip Osteoarthritis: A Systematic Review and Meta-Analysis

Background This study aimed to compare the efficacy and safety of intra-articular hyaluronic acid (HA) injection with different molecular weights (MWs) for treating hip osteoarthritis (OA). Methods A systematic literature search for relevant studies was conducted in 3 electronic databases, including PubMed, BMJ Journals, and Cochrane Library, from inception to April 2020. Extracted outcomes included visual analogue scale (VAS) (1, 3, and 6 months), Lequesne index (3 and 6 months), and adverse effects. HAs were classified into low-molecular-weight (LMW), moderate-molecular-weight (MMW), high-molecular-weight (HMW), and ultra-high-molecular-weight (UHMW) groups. Meta-analysis was performed using Review Manager 5.3. Results A total of 15 studies with 614 patients were included. Our meta-analysis showed that the HMW HA group had the best improvement in VAS and Lequesne index compared with other HA groups for all the follow-up visits. Moreover, the HMW group demonstrated significantly better improvement than the other groups in VAS at 6-month follow-up and in Lequesne index at 3- and 6-month follow-ups. Analysis for adverse effects revealed low rates of systemic adverse effects (≤0.6%) in all groups and similar rate of local adverse effects (around 10%) among the groups except for UHMW HA group (37.5%). Conclusion Among different MWs of HA for treating hip OA, HMW HA injection demonstrated the best efficacy for up to 6 months after treatment without increased risk of adverse effects. Further studies with more comprehensive data and a higher level of evidence are required to prove our results.

POS1281 HOW DOES OBESITY INFLUENCE THE FEATURES OF KNEE OSTEOARTHRITIS?

Background:Knee osteoarthritis and obesity are both major health problems. It is now admitted that the prevalence of knee osteoarthritis gets higher with obesity and that weight loss helps knee function and allows patients to avoid surgery.Objectives:The aim of this study was to study the influence of obesity on knee osteoarthritis features.Methods:A cross-sectional study was conducted in the university hospital Taher Sfar of Tunisia over a period of 6 months. Patients who had knee osteoarthritis confirmed by radiographs were included. Sociodemographic, clinical, radiological and therapeutic data were collected from medical records and visits. Obesity was defined by a body mass index (BMI) ≥30. Functional impairment was assessed by the Womac index and Lequesne index.Results:The study included 186 patients. There were 31 males and 155 femmes. The mean age was 60±10 years. The percentage of obese patients was 53,8%. The mean age was similar in both groups obese and non obese. There were more women in the obese group compared to the non obese group (p=0.0001), more patients who had diabetes mellitus and dyslipidemia (p=0.002). Non-obese patients had a shorter duration of symptoms with no statistical significance (p=0.151). Obese patients had more involvement of both knees (p<0.0001). Obesity did not have an impact on pain severity. Severity of radiological images (p=0,0001) were more frequent in obese patients. Functional impairment was similar in both groups. However, the percentage of patients having a very important functional impairment with Lequesne index was higher in obese patients (p<0.029). Obese patients also needed more physical therapy sessions (p=0.035).Conclusion:Knee osteoarthritis in obese patients is characterized with the femlae gender predominance, bilateral knee involvement, and a more severe images on radiographs. Thus the need for better control of weight and the importance of physical activity.References:[1]Coggon D, Reading I, Croft P, et al. Knee osteoarthritis and obesity. Int J Obes Relat Metab Disord J Int Assoc Study Obes 2001; 25: 622–627.Disclosure of Interests:None declared

Comparing efficacy of intraarticular single crosslinked Hyaluronan (HYAJOINT Plus) and platelet-rich plasma (PRP) versus PRP alone for treating knee osteoarthritis

Intraarticular hyaluronan or platelet-rich plasma (PRP) is widely used in the treatment of knee osteoarthritis (OA). The efficacy of combined hyaluronan with PRP remained inconclusive. This study aimed to investigate the efficacy of combined a single crosslinked hyaluronan (HYAJOINT Plus) and a single PRP versus a single PRP in patients with knee OA. In a prospective randomized-controlled trial, 85 patients with knee OA (Kellgren-Lawrence 2) were randomized to receive a single intraarticular injection of HYAJOINT Plus (3 ml, 20 mg/ml) followed by 3 ml PRP (the combined-injection group, N = 43) or a single injection of 3 ml PRP (the one-injection group, N = 42). The primary outcome was the change from baseline in the visual analog scale (VAS) pain (0–00 mm) at 6 months. Secondary outcomes included The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, Likert Scale), Lequesne index, single leg stance test (SLS), use of rescue analgesics and patient satisfaction at 1, 3 and 6 months. Seventy-eight patients were available for the intention-to-treat analysis at 6 months. Both groups improved significantly in VAS pain, WOMAC, Lequesne index and SLS at each follow-up visit (p < 0.001). Patients receiving a single PRP experienced significantly greater improvements in VAS pain than patients receiving combined injections at 1-month follow-up (adjusted mean difference: − 5.6; p = 0.017). There were no significant between-group differences in several of the second outcomes at each follow-up visit, except the WOMAC-pain and WOMAC-stiffness scores favoring the one-injection group at 1 month (p = 0.025 and p = 0.011). However, at 6-month follow-up, the combined-injection group achieved significantly better VAS pain reduction (p = 0.020). No serious adverse events occurred following injections. In conclusion, either combined injections of HYAJOINT Plus and PRP or a single PRP alone was safe and effective for 6 months in patients with Kellgren-Lawrence 2 knee OA. Combined injections of HYAJOINT Plus and PRP achieved better VAS pain reduction than a single PRP at 6 months. The results indicating a long term benefit effect of a combination of HYAJOINT Plus and PRP in a particular subset of patients with moderate knee OA need to be replicated in larger trials.ClinicalTrials.gov number NCT04315103.

Evaluation of the efficacy and safety of a combination of chondroitin sulfate and glucosamine sulfate for knee and hip osteoarthritis in real clinical practice

A combination of chondroitin and glucosamine is widely used in clinical practice as both a symptomatic and structure-modifying agent for the treatment of osteoarthritis (OA). The emergence of new drugs based on this combination substantially expands treatment options for OA therapy.Objective: to evaluate the efficacy and safety of Artroflex® that is a combination of chondroitin sulfate 400 mg and glucosamine sulfate 500 mg (CS + GS) to support joint health in patients with knee and/or hip OA.Patients and methods. When implementing an open observational research program, the results of using the CS + GS complex were assessed in 644 OA patients (74.7% women) (mean age, 58.0±14.6 years) who experienced moderate/severe pain and required to continuously take non-steroidal anti-inflammatory drugs (NSAIDs). The CS + GS complex was prescribed in a dose of 2 capsules per day for 3 months. The investigators estimated changes in pain on movement by a 0 to 10 verbal pain scale, general health (GH) by a 0–10 visual analogue scale), the Lequesne index, the need for NSAIDs, and patient satisfaction with treatment and its tolerance.Results and discussion. After 3-month therapy, there were decreases in pain intensity by 49.2±16.8%, GH scores by 45.6±18.1%, the Lequesne index from 9.0 [6.0; 13.0] to 5.0 [3.0; 9.0]; less than half (45.2%) of the patients still needed for NSAIDs. 82.2% of patients were satisfied or completely satisfied with treatment results; 89.6% reported good treatment tolerance.Adverse events (apparently associated with NSAID use) were recorded in 2.2% of cases. There were no serious complications that required CS + GS treatment discontinuation or hospitalization.Conclusion. The findings have indicated that Artroflex® used to support joint health is an effective agent that controls OA symptoms and has a good safety level.

Efficacy of Acupoints Dual-Frequency Low-Level Laser Therapy on Knee Osteoarthritis

Background. Knee osteoarthritis (OA) presented with knee pain and limitation of mobility is common, and it may become a chronic problem resulting in major loss of function, with related impaired activity of daily living. Current traditional therapy for knee OA includes pharmacological treatment and physiotherapy, but the efficacies are limited. An alternative noninvasive treatment low-level laser therapy (LLLT) applied to acupoints is still contradictory and the efficacy needs to be assessed. Methods and Materials. We conduct the randomized double-blind control study to investigate the efficacy of a dual-frequency LLLT (combines red light (780 nm) and near-infrared light (830 nm)) in patients suffering knee OA. Participates were randomly assigned into active laser therapy (ALT) and placebo laser therapy (PLT) groups. Subjects in the ALT group were separately treated by laser apparatus at the three acupoints (SP9, SP10, and EX-LE2) on their knee joints under continuous radiation for 15 min at the maximum intensity, three times per week for four weeks. The PLT group used laser apparatus of the same model according to similar procedures without laser light emission. Outcome Measurements including visual analog scale (VAS), pain pressure threshold (PPT), and Lequesne index were used. Results. A total of 30 subjects with two-sided knee OA in both groups completed the experiment. Statistically significant decreases were observed in the Lequesne index (5.27 ± 3.26 vs. 10.83 ± 3.83), conscious VAS 4 weeks after treatment (moving: 2.87 ± 1.13 vs. 5.67 ± 1.72; resting: 0.33 ± 0.62 vs. 2.67 ± 1.29), and the increase was noted in PPT (21.23 ± 1.82 kg vs. 13.02 ± 1.46 kg) in the ALT group compared with the PLT group. Conclusion. It appears that the knee OA pain and disability can be decreased after a dual-frequency LLLT applied to acupoints (SP9, SP10, and EX-LE2). The clinical efficacy of LLLT is highly related to the therapeutic settings of the laser apparatus; hence, more clinical trials with diffident parameter settings are needed to be further clarified.