Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) combined with sodium hyaluronate (HA) for the treatment of knee osteoarthritis (KOA). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, and SinoMed were searched from inception to July 2020. The quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic Reviews. The identified articles were then screened individually using EndnoteX9 for eligibility in this Meta-analysis. The heterogeneity among the articles was evaluated using I2. RESULTS: A total of 17 studies, comprising 2000 individuals, were included in this Meta-analysis. The results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with HA. Statistical analysis of clinical efficacy showed that [relative risk (RR) = 1.21, 95% confidence interval (CI) (1.12, 1.30), P < 0.01]. Statistical analysis of visual analog scale showed that [standardized mean difference (SMD) = －2.84, 95%CI (－4.01, －1.66), P < 0.01]. Western Ontario and McMaster University osteoarthritis index statistical analysis showed that [SMD = －1.57, 95% CI (－2.52, －0.61), P < 0.01]. Lysholm score statistical analysis showed that [SMD = 1.71, 95% CI (0.98, 2.44), P < 0.01]. In addition, only minor side effects, such as redness and swelling of the skin, were observed. CONCLUSIONS: Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive, well-tolerated, safe, and effective method to improve pain and functionality in patients with KOA. However, tightly controlled, randomized, large multicenter trials are warranted to validate the current findings.

Interventional Techniques for the Management of Knee Osteoarthritis: A Literature Review.

Osteoarthritis of the knee is a prevalent condition that causes pain, discomfort, and disability that can severely impact the quality of life. This literature review aims to review the various interventional pain management techniques available to treat knee osteoarthritis. It analyzes the efficacy of various interventions such as intra-articular corticosteroids, prolotherapy, viscosupplementation, platelet-rich plasma, and genicular nerve blocks with radiofrequency ablation or cryoneurolysis. We searched databases for studies published in the past 20 years. A total of 37 articles were included. The literature supports the idea that a comprehensive treatment plan consisting of the various aforementioned techniques can provide relief for patients while delaying or avoiding joint replacement surgery.

[Functionality/isokinetic work of quadriceps in patients with gonarthrosis managed with prolotherapy]. / Funcionalidad/trabajo isocinético de cuádriceps de pacientes con gonartrosis manejados con proloterapia.

Background: Prolotherapy may be a good option in the complementary treatment of knee osteoarthritis (OA) patients, specifically for the increase of functionality. Objective: To determine the effectiveness of prolotherapy in OA grade II - III in the functionality and muscular work of knee flexors and extensors. Material and methods: a double-blind randomized controlled clinical trial was conducted. It included patients diagnosed with OA grades II-III. The experimental group was infiltrated in both knees with 6 ml of 25% glucose solution and 0.05% lidocaine; control group with 0.45% saline solution and 0.05% lidocaine. All patients received a comprehensive rehabilitation program. The isokinetic work of the knee flexor and extensor muscles, pain and functionality were measured, prior to infiltration and at 3-month follow-up. To compare the difference in means, the Student's T test was applied, considering P<0.05 as significant. The project was approved by the local ethics and research committee. Results: 37 patients were recruited, 17 in the prolotherapy group. There were no intergroup differences in functionality, isokinetic knee flexor/extensor work, and pain at baseline, or during follow-up up to 12 weeks. Conclusions: In the present study we identify that both prolotherapy and saline infiltration increased functionality, strength, and decreased pain; however, no statistically significant difference was found between the two group.

Introducción: la proloterapia puede ser buena opción en el tratamiento complementario de pacientes con osteoartrosis de rodilla (OA), específicamente para el incremento de la funcionalidad. Objetivo: determinar la efectividad de la proloterapia en OA grado II-III en la funcionalidad y en el trabajo muscular de flexores y extensores de rodilla. Material y métodos: se realizó un ensayo clínico controlado aleatorizado a doble ciego. Incluyó a pacientes con el diagnostico de OA grados II-III. Al grupo experimental se les infiltraron 6 mL de solución glucosada al 25% y lidocaína al 0.05% en ambas rodillas; al grupo control con solución salina al 0.45% y lidocaína al 0.05%. Todos los pacientes recibieron un programa integral de rehabilitación. Se midió el trabajo isocinético de los músculos flexores y extensores de rodilla, dolor y funcionalidad, previa infiltración y a los tres meses de seguimiento. Para comparar la diferencia de medias, se aplicó la prueba de t de Student, considerando p < 0.05 como significativo. El proyecto se aprobó en el comité local de ética e investigación. Resultados: se reclutaron 37 pacientes, 17 en el grupo de proloterapia. No hubo diferencias intergrupo en la funcionalidad, trabajo isocinético de flexores/extensores de rodilla y dolor iniciales, ni durante el seguimiento hasta las 12 semanas. Conclusiones: en el presente estudio identificó que tanto la proloterapia como la infiltración con solución salina incrementaron la funcionalidad, fuerza y disminuyeron el dolor; sin embargo, no se encontró diferencia estadísticamente significativa entre los dos grupos.

Electroacupuncture stimulating Neixiyan (EX-LE5) and Dubi (ST35) alleviates osteoarthritis in rats induced by anterior cruciate ligament transaction affecting DNA methylation regulated transcription of miR-146a and miR-140-5p.

OBJECTIVE: To explore whether electroacupuncture (EA) could alleviate osteoarthritis (OA) through affecting the DNA methylation regulated transcription of miR-146a and miR-140-5p. METHODS: Sixty male eight-week-old Sprague-Dawley rats were divided into three groups: normal group (normal healthy rats; no treatment), model group (OA rats; no treatment) and EA group (OA rats treated with EA). Safranin O staining and modified Mankin's score were performed to evaluate the histopathological alterations and degeneration of cartilage 8 weeks after 8 consecutive weeks of treatment. Quantitative real time polymerase chain reaction (qRT-PCR) assay was employed to evaluate the expression of miR-146a in the cartilage tissue and miR-140-5p in the synovium tissue, respectively. The bisulfite sequencing analysis and quantitative methylation specific PCR (qMSP) were used to analyze the status of methylation in the regulatory regions of miR-146a and miR-140-5p. Chromatin immunoprecipitation (ChIP) assay were performed to assess the binding of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (SMAD-3) in the regulatory regions of miR-146a and miR-140-5p. Western blot analysis was performed to detect the expressions of DNA Methyltransferase 1 (DMNT1), DNA Methyltransferase 3A (DMNT3A), and DNA Methyltransferase 3A (DMNT3b), NF-κB, SMAD3 levels. RESULTS: Our results showed that EA treatment significantly upregulated miR-146a and miR-140-5p expressions. qMSP analysis showed that EA significantly decreased methylation levels of miR-140-5p regulated region and miR-146a promoter in OA cartilage and synovium. Bisulfite DNA sequencing (BDS) and ChIP analysis showed that EA significantly increased binding affinity of SMAD3 and NF-kB on the hypermethylated miR-140 regulatory region and miR-146a promoter, respectively. Western Blot analysis demonstrated that EA also significantly decreased expressions of methylation related proteins- DMNT1, DMNT3a, and DMNT3b as well as NF-κB and SMAD3. CONCLUSIONS: Electroacupuncture stimulating Neixiyan (EX-LE5) and Dubi (ST35) may alleviate OA affecting the DNA methylation regulated transcription of miR-146a and miR-140-5p.

Comparison of the effects of transcutaneous electrical nerve stimulation and interferential current therapies in central sensitization in patients with knee osteoarthritis.

Background: This study is primarily aimed to determine whether transcutaneous electrical nerve stimulation (TENS) and interferential current (IFC) treatments have any effect on central sensitization (CS) in patients with knee osteoarthritis (OA) and to investigate which treatment is more effective. Methods: In this randomized controlled trial, 80 patients were randomized into four treatment groups: TENS, Plasebo-TENS, IFC, and Plasebo-IFC. All interventions were applied 5 times a week for 2 weeks. Primary outcome was pressure pain threshold (PPT), which is accepted as the objective indicator of CS, at the painful knee and at the shoulder as a painless distant point. Other outcome measures were the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index, Timed Up and Go Test, pain catastrophizing scale, Beck Depression Inventory, and Tampa Scale of Kinesiophobia. Results: All assessment parameters were improved, without a significant difference among the groups except PPT. PPT scores were significantly improved in TENS and IFC groups when compared with the sham groups at 2 weeks and 3 months. In addition, this improvement was even more pronounced in the TENS group. Multivariable logistic regression analysis showed that the patient's inclusion in the TENS group, an initial high PPT, and an initial low VAS score were independent risk factors for improvement in the PPT. Conclusions: This study shows that TENS and IFC reduced pain sensitivity as compared to placebo groups in patients with knee OA. This effect was more pronounced in the TENS group.

Acupotomy ameliorates subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis by regulating bone morphogenetic protein 2-Smad1 pathway.

OBJECTIVE: To investigate the effects of acupotomy on the subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis (KOA). METHODS: The rabbits were divided into blank control, model, acupotomy and electroacupuncture (EA) groups, with 12 rabbits in each. Modified Videman's method was used to prepare KOA model. The acupotomy and EA group were given indicated intervention for 3 weeks. The behavior of rabbits in each group was recorded. Subsequently, cartilage-subchondral bone units were obtained and morphological changes were observed by optical microscope and micro computed tomography. Compression test was used to detect the mechanical properties of subchondral bone, Western blot and real-time polymerase chain reaction (RT-PCR) were applied to detect the expression of bone morphogenetic protein 2-Smad1 (BMP2-Smad1) pathway in subchondral bone. RESULTS: Compared with the control group, rabbits in the KOA group showed lameness, knee pain, and cartilage degradation; the subchondral bone showed active resorption, the mechanical properties decreased significantly and the BMP2-Smad1 pathway downregulated significantly. Both acupotomy and EA intervention could increase the thickness of trabecular bone (Tb. Th), the bone volume fraction (BV/TV) and the thickness of subchondral bone plate, reduce the separation of trabecular bone (Tb. Sp), improve the maximum load and elastic modulus of subchondral bone, and effectively delay cartilage degeneration in KOA rabbits. This process may be achieved through upregulation the related proteins of BMP2-Smad1 pathway. The maximum load and elastic modulus of subchondral bone in the acupotomy group were slightly better than those in the EA group. CONCLUSIONS: Acupotomy could effectively protect cartilage by inhibiting abnormal bone resorption and improving mechanical properties of subchondral bone thorough the related proteins of BMP2-Smad1 pathway in KOA rabbits.

Protocol to establish auxiliary diagnostic model for knee osteoarthritis functional testing equipment.

In China, 50% of Knee Osteoarthritis (KOA) patients will be treated with Traditional Chinese Medicine or a combination of Traditional Chinese and Western Medicine, which call for objective efficacy evaluation methods. The collection, processing and fusion of multi-source data were taken as the main methods, with 150 KOA patients and 100 healthy people as an example to design prospective clinical tests. Data were collected with tongue inspection APP, infrared instrument and channel instrument, etc. And the analysis, screening, fusion and modelling of multi-source data were conducted. The traditional clinical tests have been combined with the customized information platform in this study, which is convenient for clinical tests, medical follow-ups and timely feedback to statistical analysis of data.

Effects of Tuina on cartilage degradation and chondrocyte terminal differentiation in rats with knee osteoarthritis (KOA) via the Wnt/β-catenin signaling pathway / 针灸推拿医学（英文版）

Objective: To investigate the therapeutic effects of Tuina (Chinese therapeutic massage) in a knee osteoarthritis (KOA) rat model and its influence on proteins associated with the Wnt/β-catenin signaling pathway. Methods: A total of 32 specific-pathogen-free grade Sprague-Dawley rats were used. Eight rats were randomly selected as the control group (CG). The remaining 24 rats underwent intra-articular injections with 0.2 mL of 4％ papain to prepare the KOA rat models. After the model was established, the 24 rats were randomly and equally assigned to 3 groups, including a model group (MG), a Tuina group (TG), and a positive medicine group (PMG), with 8 rats in each group. The Lequesne score was applied to evaluate the success of model development. After the model was successfully established, the CG did not receive any intervention, and the TG was treated with local, clockwise annular Rou-Kneading around the knee joint with the thumbs. The pressure in the longitudinal direction was 3 N, and the frequency was designed to be 120-140 times/min for 15 min, followed by flexing the joint 10 times. The PMG was intragastrically administered with celecoxib [24 mg/(kg·bw)] every day. These interventions were performed once a day, 6 d per week, for a total of 4 weeks. After treatment, the Lequesne score was applied again to assess the severity of the KOA in the rats; hematoxylin-eosin (HE) staining and a mixture of equal volumes of aqueous solutions of safranin O-fast green were used to stain and observe the cartilage morphology and structure; the modified Mankin score was applied to evaluate the pathology; enzyme-linked immunosorbent assay method was used to quantify the C-telopeptide fragments of type Ⅱ collagen (CTX-Ⅱ) and cartilage oligomeric matrix protein (COMP); Western blotting was then applied to quantify Wnt4, β-catenin, matrix metalloproteinase 13 (MMP-13), and bone morphogenetic protein 2 (BMP-2) protein expression; immunohistochemistry was conducted to determine the percentage of collagen type X (ColX)-positive cells. Results: The Lequesne score of the TG and PMG was both lower than that of the MG (P<0.01); the HE staining, safranin O-fast green stained morphology and structure, and modified Mankin scores of the TG and the PMG were also better than those in the MG (P<0.01). Compared with the CG, the amounts of CTX-Ⅱ and COMP in the serum were significantly increased (P<0.01); the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins in the cartilage tissue was significantly increased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly increased (P<0.01) in the MG. In comparison with those in the MG, the amounts of CTX-Ⅱ and COMP were significantly decreased (P<0.01), the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins was significantly decreased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG and PMG. Compared with the PMG, the contents of CTX-Ⅱ and COMP and the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins were decreased (P<0.05 or P<0.01); the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG. Conclusion: Tuina can relieve the degeneration of KOA, and the mechanism may be related to the down-regulation of the Wnt/β-catenin signaling pathway, the decrease in MMP-13 and BMP-2 protein expression, the reduction in chondrocyte extracellular matrix degradation, and slowing down the terminal cell differentiation.

Effects of different moxibustion time on knee cartilage morphology and the expression of TNF-α and IL-10 in rats with knee osteoarthritis / 针灸推拿医学（英文版）

Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.

Clinical study of intra-articular injection of autologous PRP combined with Tongbi San fumigation in the treatment of early knee osteoarthritis / 国际中医中药杂志

Objective:To evaluate the efficacy of intra-articular injection of autologous platelet-rich plasma (PRP) combined with Tongbi Powder fumigation in the treatment of early knee osteoarthritis (KOA).Methods:Randomized controlled trial. Totally 160 patients with KOA in Tai'an Second Hospital of Traditional Chinese Medicine were enrolled between March 2021 and March 2022. According to random number table method, they were divided into two groups, with 80 cases in each group. The control group was given routine treatment, while observation group was given intra-articular injection of autologous PRP combined with Tongbi Powder fumigation. All were treated for 3 weeks. The knee function was evaluated by Western Ontario and McMaster University (WOMAC) osteoarthritis index. The activities of daily living were evaluated by Lysholm knee scale (LKS). The pain degree was evaluated by VAS. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The adverse reactions during treatment were observed and recorded. The clinical efficacy was evaluated.Results:The total effective rate of the observation group was 95.0% (76/80), and that of the control group was 77.5% (62/80), with statistical significance ( χ2=10.33, P<0.01). At 1, 3 and 6 months after treatment, the WOMAC score of the observation group was lower than that of the control group ( F=15.63, P<0.01), the LKS score was higher than that of the control group ( F=55.23, P<0.01), and the VAS score was lower than that of the control group ( F=11.93, P<0.01). After treatment, the observation group IL-1β [(51.75±2.74)μg/L vs. (63.38±3.31) μg/L, t=24.21], TNF- α [(10.58±1.25) μg/L vs. (11.62±1.84) μg/L, t=4.18] were lower than those in the control group ( P<0.01). The incidence of adverse reactions was 10.0% (8/80) in the observation group and 7.5% (6/80) in the control group, without statistical significance ( χ2=0.31, P=0.576). Conclusion:Intra-articular injection of autologous PRP combined with Tongbi San fumigation can effectively improve knee function and activities of living ability, relieve pain symptoms, reduce inflammatory response and improve clinical curative effect in early KOA.

[Effects of acupotomy on partial movement gait and serum tumor necrosis factor-α, interleukin-1ß in patients with knee osteoarthritis].

OBJECTIVE: To explore effects of acupotomy on pain, function, gait and serum inflammatory factors in patients with knee osteoarthritis(KOA). METHODS: From December 2017 to June 2019, 110 patients with KOA were collected and divided into acupotomy group(56 cases) and western medicine group(54 cases) by using random number table method. In acupotomy group, there were 16 males and 40 females, aged from 46 to 74 years old with an average of (62.98±6.68) years old, the course of disease ranged from 1 to 240 months with an average of 24.5(15.25, 33.00) months;were treated with acupotomy on the pain points around knee joint once a week for 3 weeks. In western medicine group, there were 18 males and 36 females, aged from 47 to 73 years old with an average of (64.19±5.98 ) years old;the course of disease ranged from 1 to 220 months with an average of 25.00(13.75, 33.00) months;were took celecoxib capsule orally, 200 mg once a day for 3 weeks. Oxford Knee Score(OKS) was performed before treatment, 3 weeks and 3 months after treatment. Gait kinematics analysis and serum levels of tumor necrosis factor-α(TNF-α) and interleukin-1ß (IL-1ß) were measured before and after treatment for 3 weeks. RESULTS: All patients were followed up from 6 to 24 months with an average of(15.03±4.55) months. OKS between two groups decreased significantly at 3 weeks and 3 months after treatment(P<0.001). Functional scores and overall scores in acupotomology group were significantly decreased at 3 months compared with 3 weeks after treatment(P<0.001). OKS of acupotomy group were significantly lower than those of western medicine group at 3 weeks and 3 months after treatment(P<0.05). Gait speed, frequency and length between two groups were significantly improved at 3 weeks after treatment(P<0.05). At 3 weeks after treatment, gait freguency of acupotomy group was significantly improved compared with western medicine group(P<0.05). TNF-α and IL-1ß were significantly lower in both groups at 3 weeks after treatment than before treatment(P<0.05). At 3 weeks after treatment, level of IL-1 ß was lower in western medicine group than in acupotomy group(P<0.05), and difference in TNF-α level was not statistically significant(P>0.05). CONCLUSION: Acupotomology of pain points could significantly improve pain, function, gait, and decreased serum inflammatory factors at early to mid stage of KOA patients, in particular, it is superior to non-steroidal anti-inflammatory drugs in terms of knee function recovery and cadence improvement.

Intra-articular Infiltration of Platelet-Rich Plasma versus Hyaluronic Acid in Patients with Primary Knee Osteoarthritis: Preliminary Results from a Randomized Clinical Trial / Infiltração intraarticular de plasma rico em plaquetas versus ácido hialurônico em pacientes com osteoartrose primária do joelho: Ensaio clínico randomizado com resultados preliminares

Abstract Objective The present study aimed to compare the effects of intraarticular infiltration of platelet-rich plasma with those of hyaluronic acid infiltration in the treatment of patients with primary knee osteoarthritis. Methods A randomized clinical trial was conducted with 29 patients who received an intraarticular infiltration with hyaluronic acid (control group) or platelet-rich plasma. Clinical outcomes were assessed using the visual analog scale for pain and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before and after the intervention. In addition, the posttreatment adverse effects were recorded. Categorical variables were analyzed using the chi-square and Fisher exact tests, whereas continuous variables were analyzed using the Student t test, analysis of variance, and the Wilcoxon test; all calculations were performed with the Stats package of the R software. Results An independent analysis of each group revealed a statistical difference within the first months, with improvement in the pain and function scores, but worsening on the 6th month after the procedure. There was no difference in the outcomes between the groups receiving hyaluronic acid or platelet-rich plasma. There was no serious adverse effect or allergic reaction during the entire follow-up period. Conclusion Intraarticular infiltration with hyaluronic acid or platelet-rich plasma in patients with primary knee gonarthrosis resulted in temporary improvement of functional symptoms and pain. There was no difference between interventions.

Resumo Objetivo Comparar o efeito da infiltração intraarticular do plasma rico em plaqueta com a do ácido hialurônico no tratamento de pacientes com osteoartrose primária de joelho. Métodos Realizou-se um ensaio clínico randomizado com 29 pacientes, sendo um grupo submetido à infiltração com ácido hialurônico (controle) e o outro com plasma rico em plaquetas. Os desfechos clínicos avaliados foram a escala visual analógica da dor; o questionário Western Ontario and McMaster Universities Arthritis Index (WOMAC), antes e depois da intervenção; e os efeitos adversos após as aplicações. Utilizou-se os testes do qui-quadrado e exato de Fisher para as variáveis categóricas, e o teste t de Student, análise de variância, e Wilcoxon para as variáveis contínuas, através do software R. Resultados A análise independente de cada grupo revelou uma diferença estatística nos meses iniciais, com melhora dos escores de dor e função; porém, com piora no 6° mês após o procedimento. Não houve diferença dos desfechos avaliados entre os grupos que foram submetidos à infiltração com ácido hialurônico ou com plasma rico em plaquetas. Não houve efeito adverso grave ou reação alérgica durante todo o seguimento. Conclusão A infiltração intraarticular com ácido hialurônico ou plasma rico em plaquetas nos joelhos dos pacientes com gonartrose primária apresentou melhora temporária dos sintomas de função e dor. Não houve diferença entre as duas intervenções.

Acupotomy inhibits aberrant formation of subchondral bone through regulating osteoprotegerin/receptor activator of nuclear factor-κB ligand pathway in rabbits with knee osteoarthritis induced by modified Videman method.

OBJECTIVE: To investigate the effects of acupotomy on inhibiting abnormal formation of subchondral bone in rabbits with knee osteoarthritis (KOA). METHODS: A total of 24 New Zealand rabbits were randomly divided into four groups of 6 rabbits each [control, model, electroacupuncture (EA) and acupotomy]. Eighteen KOA model rabbits were established using a modified Videman method. Rabbits in EA and acupotomy groups received the intervention for 3 weeks. Then, the cartilage and subchondral bone unit were obtained and the histomorphological changes were recorded. Osteo-protegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in subchondral bone were evaluated by Western blotting, real-time polymerase chain reaction and immunohistochemistry. RESULTS: Compared with the model group, both the acupotomy and EA groups showed a significant decrease in the Lequesne index (both 0.01) and Mankin score ( 0.01, < 0.05). In addition, both EA and acupotomy groups had a higher expression of total articular cartilage (TAC) ( 0.05, < 0.01) and lower expression of articular calcified cartilage (ACC)/TAC ( 0.05, < 0.05) compared with the model group. The thickness of the subchondral bone plate in EA and acupotomy groups were decreased (both 0.01) compared to the model group. Moreover, trabecular bone volume (BV/TV), protein and relative expression of OPG and the ratio of OPG/RANKL in the subchondral bone of acupotomy group were decreased statistically significant, while these parameters were not significantly changed in the EA group compared with the model group. CONCLUSIONS: In the rabbit model of KOA, acupotomy inhibits aberrant formation of subchondral bone by suppressing OPG/RANKL ratio as a potential therapy for KOA.

Effect of manipulation on cartilage in rats with knee osteoarthritis based on the Rho-associated protein kinase/LIM kinase 1/Cofilin signaling pathways.

OBJECTIVE: To investigate the effect of manipulation treatment on knee osteoarthritis rats and the effect on Rho-associated protein kinase (ROCK)/LIM-kinase1 (LIMK1)/Cofilin signaling pathway. METHOD: Fifty Specific pathogen Free Sprague-Dawley rats were randomly divided into five groups ( = 8 each): blank group, model group, manipulation group, celecoxib group, and manipulation combined with celecoxib group (MC group). The osteoarthritis model was established by injecting 0.2 mL 4% papain into the articular disc of the rats. After successfully establishing the model, we treated the manipulation group with pushing manipulation using one-finger-meditation to the Neixiyan (EX-LE4), Waixiyan (EX-LE5), Xuehai (SP10), Liangqiu (ST34), and Zusanli (ST36) acupoints for 10 min each time. Also, the celecoxib group was gavaged with 24 mg•kg•d celecoxib, while the MC group was treated using both of these two methods. After four weeks, the cartilage of the right femur was removed for hematoxylin-eosin staining of the cartilage tissue. The expressions of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in serum were observed using the enzyme-linked immunosorbent assay. Besides, we detected the expressions of ROCK, LIMK1, Phospho-LIM-kinase1 (Phospho-LIMK1), Cofilin, and Phospho-Cofilin by Western blot. RESULTS: Compared to the model group, the manipulation group, celecoxib group, and MC group all exhibited superior results concerning pathological morphologic changes of cartilage, as observed by hematoxylin-eosin staining and calculated using the Mankin score. Besides, in contrast to the blank group, the model group exhibited elevated serum levels of IL-1ß and TNF-α ( 0.01), while the expression of ROCK, LIMK1, Phospho-LIMK1, Cofilin, and Phospho-Cofilin in cartilage were all higher ( 0.01). Also, the serum levels of IL-1ß and TNF-α in each treatment group were lower (0.01) than in the model group. Moreover, there were lower expressions of ROCK, LIMK1, Phospho-LIMK1, Cofilin, and Phospho-Cofilin in cartilage in the manipulation group and the MC group (< 0.01). Compared with the model group, the expression of ROCK, LIMK1, Phospho-LIMK1, Cofilin, and Phospho-Cofilin in cartilage in the celecoxib group were not statistically different ( > 0.05). CONCLUSION: In this study, we established that manipulation has a better curative effect than celecoxib. Manipulation inhibits the development of cytoskeleton damage in cartilage and slows articular degeneration by regulating the expression of related proteins in the cytoskeletal signaling pathway.

Effects of Intra-articular Coinjections of Hyaluronic Acid and Hypertonic Dextrose on Knee Osteoarthritis: A Prospective, Randomized, Double-Blind Trial.

OBJECTIVE: To determine whether intra-articular coinjection with hypertonic dextrose improves the outcome of hyaluronic acid (HA) prolotherapy for knee osteoarthritis (OA). DESIGN: Prospective, randomized, double-blind trial. SETTING: Medical center in Taiwan. PARTICIPANTS: In total, 104 participants who fulfilled the American College of Rheumatology clinical and radiographic criteria for knee OA with a Kellgren-Lawrence score of 2 or 3 were recruited (N=104). INTERVENTIONS: The participants were blocked randomized to the treatment (HA and hypertonic dextrose) or control (HA and normal saline) group. Ultrasound-guided knee intra-articular injections were administered once a week for 3 weeks. MAIN OUTCOME MEASURES: The primary outcomes were performance-based physical function measures (regular and fastest walking speed, stair climbing time, and chair rising time), and the secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). The outcome measures were assessed before the injections and at 1 week and 1, 3, and 6 months after the injections. The data were analyzed through repeated-measures analysis of covariance. RESULTS: Significant intergroup difference-in-differences favoring the treatment group were observed for improvements in stair climbing time (-1.6; 95% confidence interval, -8.56 to 4.16; P=.38) and WOMAC physical function (-21.2; 95% confidence interval, -126.05 to 103.83; P = .045) at 6 months. The group×time interaction effects favored the treatment group for regular (P=.001) and fastest walking speed (P=.001) and chair rising time (P=.038); WOMAC stiffness (P < .001) and physical function (P = .003); and KOOS for pain (P = .035), other symptoms (P=.022), and quality of life (P=.012). CONCLUSIONS: Compared with HA plus normal saline coinjections, HA plus dextrose coinjections resulted in more significant improvements in stair climbing time and physical function at 6 months, effectively decreased pain, and improved physical function and physical functional performance from 1 week to 6 months. HA plus dextrose coinjections could be a suitable adjuvant therapy for patients with knee OA.

Effect of Neuromuscular Electrical Stimulation During Walking on Pain Sensitivity in Women With Obesity With Knee Pain: A Randomized Controlled Trial.

OBJECTIVE: To assess the extent to which pain sensitivity is altered in women with obesity with frequent knee symptoms who walk with either a hybrid training system (HTS) that provides antagonist muscle electrical stimulation vs sensory transcutaneous electrical nerve stimulation (TENS). DESIGN: Randomized, double-blinded, controlled trial. SETTING: University-based fitness center. PARTICIPANTS: Twenty-eight women (N=28) with obesity, aged 40-70 years, with daily knee symptoms. INTERVENTIONS: Participants were randomized to 12 weeks of biweekly 30-minute walking exercise with either HTS (HTSW group) or sensory TENS (control group). MAIN OUTCOME MEASURES: Pressure pain thresholds (PPTs) at the more symptomatic knee (local PPT) and PPT at the ipsilateral pain-free wrist (remote PPT). RESULTS: After adjustment for preintervention values and body mass index (BMI), there was a statistically significant improvement in local PPT in the HTSW group compared with the control group (P=.039). After adjustment for pretraining value, age, and BMI, changes in remote PPT when comparing groups did not reach statistical significance, although the HTS group tended to demonstrate increased remote PPT (P=.052) compared with the control group. Moreover, after adjustment for pretraining value, knee pain, and quality of life, comparing groups did not reach statistical significance, although the HTS group tended to demonstrate decreased knee pain (P=.069) compared with the control group. CONCLUSIONS: Augmentation of walking exercise with HTS was more effective than application of sensory TENS in improving local pain sensitivity at the knee but not at the wrist in women with obesity with frequent knee symptoms.

Clinical observation of acupuncture combined with sitting-position knee-adjustment manipulations for patellofemoral arthritis / 针灸推拿医学（英文版）

Objective: To observe the efficacy of acupuncture combined with sitting-position knee-adjustment manipulations in treating patellofemoral osteoarthritis. Methods: Ninety-two patients with patellofemoral osteoarthritis were randomized into an observation group and a medication group, with 46 cases in each group. The observation group received acupuncture and sitting-position knee-adjustment manipulations, and the medication group received oral celecoxib capsules. After 8-week treatment, changes in the short-form McGill pain questionnaire (SF-MPQ) and Lysholm knee scoring scale (LKSS) scores were observed, and the clinical efficacy was compared.Results: The total effective rate was 87.0％ in the observation group and 63.0％ in the control group; the between- group difference was statistically significant. Before treatment, there were no significant differences in the SF-MPQ score or LKSS score (P>0.05). After 8-week treatment, the SF-MPQ [including pain rating index (PRI), visual analog scale (VAS), and present pain intensity (PPI)] and LKSS scores showed notable changes in both groups (P<0.05); the SF-MPQ and LKSS scores in the observation group were significantly different from those in the control group (P<0.05).Conclusion: Combining acupuncture and sitting-position knee-adjustment manipulations can reduce pain and ameliorate joint function in patients with patellofemoral osteoarthritis, producing more significant efficacy than oral celecoxib capsules.

Therapeutic effect of sodium hyaluronate combined with glucosamine sulfate on patients with knee osteoarthritis / 中华地方病学杂志

Objective:To explore the therapeutic effect of sodium hyaluronate combined with glucosamine sulfate in the treatment of knee osteoarthritis.Methods:A total of 90 outpatients and inpatients with knee osteoarthritis who visited the Department of Orthopedics and Traumatology, Daishan County Hospital of Traditional Chinese Medicine from January to June 2020 were selected, and they were divided into sodium hyaluronate group (control group) and sodium hyaluronate combined with glucosamine sulfate group (observation group) by random number table method, with 45 patients in each group. Visual analog scale (VAS) score was used to evaluate the changes of pain in the two groups before treatment, 5 weeks and 6 months after treatment, respectively; at the same time, the total effective rate of 5 weeks and 6 months after treatment was compared between the two groups.Results:Before treatment, there was no significant difference in VAS scores [(7.4 ± 1.5) vs (7.3 ± 1.7) points] between the two groups ( t = 0.24, P = 0.812); at 5 weeks [(5.3 ± 1.1) vs (4.1 ± 1.2) points] and 6 months after treatment [(4.0 ± 0.8) vs (3.2 ± 0.9) points], the VAS scores of the observation group were significantly lower than those of the control group, and the differences were statistically significant ( t = 5.54, 5.32, P < 0.001). Compared with the same group before treatment, VAS scores were lower in the two groups at 5 weeks and 6 months after treatment, and the differences were statistically significant ( P < 0.05). At 5 weeks after treatment, there was no significant difference in the total effective rates [44.4% (20/45) vs 48.9% (22/45)] between the two groups (χ 2 = 0.18, P = 0.672); at 6 months after treatment, the total effective rate of the observation group (91.1%, 41/45) was significantly higher than that of the control group (66.7%, 30/45), and the difference was statistically significant (χ 2 = 8.07, P = 0.004). Conclusion:Sodium hyaluronate combined with glucosamine sulfate can significantly reduce the pain in patients with knee osteoarthritis, the total effective rate is higher, and is better than the effect of sodium hyaluronate alone.

Clinical study on thermal moxibustion combined with Duhuo Jisheng Decoction for the patients with knee osteoarthritis and liver and kidney deficiency syndrome / 国际中医中药杂志

Objective:To explore the clinical efficacy of thermal moxibustion combined with Duhuo Jisheng Decoction in the treatment of liver and kidney deficiency syndrome of knee osteoarthritis (KOA).Methods:From January 2020 to January 2021, 124 KOA patients with liver and kidney deficiency syndrome, who met the inclusion criteria, were divided into 2 groups according to the random number table method, with 62 in each group. The control group was treated with Duhuo Jisheng Decoction, and the observation group was treated with thermal moxibustion on the basis of the control group. Both groups were treated for 28 days. TCM symptom scores were performed before and after treatment, the Osteoarthritis Index of Western Ontario and McMaster University (WOMAC) was used to evaluate joint function. ELISA was used to detect serum insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), transforming growth factor-β1 (TGF-β1), IL-1β, IL-6, TNF-α levels, and the clinical efficacy was evaluated.Results:The total effective rate was 91.9% (57/62) in the observation group and 77.4% (48/62) in the control group, and there was significant difference between two groups ( χ2=5.04, P=0.025). After treatment, the TCM symptom score and WOMAC score of the observation group were significantly lower than those of the control group ( t values were 11.33 and 12.23, respectively, all Ps<0.01). After treatment, the serum levels of IGF-1 [(15.63±2.03) ng/L vs. (12.78±1.57) ng/L, t=8.75], FGF-2 [(30.26±5.37) ng/L vs. (26.31±1.94) ng/L, t=5.45] and TGF-β1[(30.39±6.71)μg/L vs. (24.31±5.12) μg/L, t=5.67] in the observation group were significantly higher than those in the control group ( P<0.01), while the levels of IL-1β [(12.50±3.36) ng/L vs. (16.09±4.90) ng/L, t=4.76], IL-6 [(10.59±3.28) ng/L vs. (21.75 ± 4.09) ng/L, t=16.76] and TNF-α [(4.04±1.92) ng/L vs. (6.48±1.43) ng/L, t=8.03] in the observation group were significantly lower than those in the control group ( P<0.01). There was no adverse events from both groups during treatment. Conclusion:Thermal moxibustion combined with Duhuo Jisheng Ddecoction can alleviate the joint pain of KOA patients with liver and kidney deficiency syndrome, promote cartilage repair and improve the clinical curative effect.

Acupuncture treatment for knee osteoarthritis: an overview of systematic reviews / 国际中医中药杂志

Objective:To revaluate the systematic review/meta-analysis on efficacy and safety of acupuncture treatment for knee osteoarthritis.Methods:We searched CNKI, VIP, WangFang, CBM, PubMed, Cochrane Library databases, Embase, from inception to December 15, 2020, to retrieve systematic reviews and/or meta analyses on the treatment of knee osteoarthritis with acupuncture and moxibustion. Two researchers independently screened the literature and extracted data, used the AMSTAR2 scale to evaluate the methodological quality, and used the GRADE system to grade the quality of evidence.Results:A total of 11 systematic evaluations were included, including 44 outcomes. Methodological evaluation showed that all 11 literatures were of very low quality. The GRADE system evaluation showed that there were 13 intermediate evidences, 12 low evidences, and 19 very low evidences.Conclusion:The results of the existing systematic reviews show that acupuncture and moxibustion have a certain efficacy in the treatment of knee osteoarthritis, but the methodology and evidence level of the included studies are low, so this conclusion needs to be verified by further high-quality studies.