Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis

Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.

Therapeutic effect of San Bi Tang combined with glucosamine sulfate capsules in cold-dampness-type knee osteoarthritis

BACKGROUND Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease,but its pathogenesis is not fully understood,and its clinical treatment has limitations.Glucosamine sulfate capsules are commonly used for treating arthritis,and San Bi Tang is a classic formula of traditional Chinese medicine(TCM)that has the effects of warming yang,dispelling dampness,relaxing muscles,and activating collaterals.This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects.AIM To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis.METHODS A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each.The control group received only treatment with glucosamine sulfate capsules,while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk.The patients’knee joint functions,liver and kidney function indicators,adverse reactions,and vital signs were evaluated and analyzed using SPSS 26.0 software.RESULTS Before treatment,the two groups’genders,ages,and scores were not significantly different,indicating comparability.Both groups’scores improved after treatment,which could indicate pain and knee joint function improvement,but the test group had better scores.The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher.Before and after treatment,there were no abnormalities in the patients’liver and kidney function indicators.CONCLUSION The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.

Comparison between Care Strategies for Patients with Osteoarthritis of the Hands Based on the Use of Joint Protection, Assistive Technology and Exercises

Background: Osteoarthritis (OA) is a disabling disease that can affect 6% to 12% of the adult population and more than a third of people over 65 years of age. Purpose: To assess whether a group of people with hand osteoarthritis (hOA) who received different types of treatment improved their function after two years of follow-up. Method: The entire sample (n = 97) underwent three follow-up assessments regarding anthropometric parameters of the upper limbs and ability to perform functional activities. Subsequently, the sample was divided into two groups for the intervention periods, called the First Period (n = 73) and the Second Period (n = 24);the First Period kept the same protocol with orientations, and the Second Period went to an intervention with orientation strength exercises and use of orthosis. Findings: In the separate analysis of the three questions of the DASH pain module, no differences were found between the assessment moments for groups of guidelines, treatment, or symptoms. Significant effects were observed for F(2, 162) = 3.5, p = 0.033, η2 = 0.04, and interaction for moments and intervention F(2, 162) = 4.3, p = 0.016, η2 = 0.05. Implications: It can be concluded that only guidance treatment does not benefit patients with hand osteoarthritis. In contrast, guidance, exercise, and orthosis treatment can significantly improve the disease.

The Use of Biologic Treatments for Osteoarthritis: A Review

Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatments for the disease. Biologic therapies have been touted as an adjunct, or even alternative to established treatments for osteoarthritis. The term “biologics” refers to protein-based therapeutics that are derived from the proteins of living organisms. These treatments include, but are not limited to: autologous blood products such as platelet rich plasma (PRP), cell therapies such as autologous chondrocyte implantation (ACI) and mesenchymal stem cells, growth factors and cytokines, gene therapy. Aim: This study aims to provide a clear definition of these technologies and describe the evidence supporting their clinical efficacy to treat osteoarthritis. This is to provide clarity to both clinicians and patients on the range of technologies available. Method: Literature databases Embase and PubMed were searched for keywords such as “biologic”, “osteoarthritis”. Results: The literature identified 4 primary categories of biologic treatments for osteoarthritis: stem cell therapy, somatic cell therapy, protein therapy and gene therapy. The evidence level varied in its quality from treatment to treatment, as did the conclusions of published studies. Conclusion: Autologous chondrocyte therapy had the most convincing evidence to support its use as a treatment for osteoarthritis, however, current methods of use produced variable results. Other treatments such as platelet rich plasma and bone marrow derived stem cells show promise as potential future therapies, with more refinement, but evidence does not support their use currently. Other treatments including autologous stem cells should be avoided until there is a greater quantity and quality of evidence supporting their use.

Adhesive hydrogels in osteoarthritis:from design to application

Osteoarthritis(OA)is the most common type of degenerative joint disease which affects 7%of the global population and more than 500 million people worldwide.One research frontier is the development of hydrogels for OA treatment,which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives.Both approaches address the big challenge:establishing stable integration of such delivery systems or implants.Adhesive hydrogels provide possible solutions to this challenge.However,few studies have described the current advances in using adhesive hydrogel for OA treatment.This review summarizes the commonly used hydrogels with their adhesion mechanisms and components.Additionally,recognizing that OA is a complex disease involving different biological mechanisms,the bioactive therapeutic strategies are also presented.By presenting the adhesive hydrogels in an interdisciplinary way,including both the fields of chemistry and biology,this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Factors affecting osteogenesis and chondrogenic differentiation of mesenchymal stem cells in osteoarthritis

Osteoarthritis(OA)is a common degenerative joint disease that often involves progressive cartilage degeneration and bone destruction of subchondral bone.At present,clinical treatment is mainly for pain relief,and there are no effective methods to delay the progression of the disease.When this disease progresses to the advanced stage,the only treatment option for most patients is total knee replacement surgery,which causes patients great pain and anxiety.As a type of stem cell,mesenchymal stem cells(MSCs)have multidirectional differentiation potential.The osteogenic differentiation and chondrogenic differentiation of MSCs can play vital roles in the treatment of OA,as they can relieve pain in patients and improve joint function.The differentiation direction of MSCs is accurately controlled by a variety of signaling pathways,so there are many factors that can affect the differentiation direction of MSCs by acting on these signaling pathways.When MSCs are applied to OA treatment,the microenvironment of the joints,injected drugs,scaffold materials,source of MSCs and other factors exert specific impacts on the differentiation direction of MSCs.This review aims to summarize the mechanisms by which these factors influence MSC differentiation to produce better curative effects when MSCs are applied clinically in the future.

Application of mesenchymal stem cell therapy for the treatment of osteoarthritis of the knee: A concise review

Osteoarthritis(OA) refers to a chronic joint disease characterized by degenerative changes of articular cartilage and secondary bone hyperplasia. Since articular cartilage has a special structure, namely the absence of blood vessels as well as the low conversion rate of chondrocytes in the cartilage matrix, the treatment faces numerous clinical challenges. Traditional OA treatment(e.g., arthroscopic debridement, microfracture, autologous or allogeneic cartilage transplantation,chondrocyte transplantation) is primarily symptomatic treatment and pain management, which cannot contribute to regenerating degenerated cartilage or reducing joint inflammation. Also, the generated mixed fibrous cartilage tissue is not the same as natural hyaline cartilage. Mesenchymal stem cells(MSCs) have turned into the most extensively explored new therapeutic drugs in cell-based OA treatment as a result of their ability to differentiate into chondrocytes and their immunomodulatory properties. In this study, the preliminary results of preclinical(OA animal model)/clinical trials regarding the effects of MSCs on cartilage repair of knee joints are briefly summarized, which lay a solid application basis for more and deeper clinical studies on cell-based OA treatment.

A comparison of Kneipp hydrotherapy with conventional physiotherapy in the treatment of osteoarthritis: a pilot trial

BACKGROUND： An increasingly aging population implies an increasing prevalence of osteoarthritis （OA） of hip or knee. It has been ascertained that unspecific hydrotherapy of OA according to Sebastian Kneipp not only improves the range of mobility but also reduces pain significantly and increases the quality of life of the patients affected. OBJECTIVE： The main aim of this pilot study was to determine the effects of hydrotherapy in comparison to conventional physiotherapy, and to analyze the feasibility of the study design under clinical circumstances. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： The study design is a prospective randomized controlled three-arm clinical pilot trial, carried out at a specialist clinic for integrative medicine. Thirty patients diagnosed with symptomatic OA of hip or knee and radiologic findings were randomly assigned to one of two intervention groups and a control group： hydrotherapy （group 1）, physiotherapy （group 2）, and both physiotherapy and hydrotherapy （group 3, control group） of the affected joint. MAIN OUTCOME MEASURES： Primary outcome： pain intensity of the affected joint in the course of inpatient treatment; secondary outcome： health-related quality of life, joint-specific pain and mobility in the course of the study. RESULTS： Concerning the main outcome, intervention group 1 showed most beneficial effects in the course of inpatient treatment, followed by groups 3 and 2, and also the indirect flexion ability of hip or knee together with the general patient mobility through the ＂timed up and go＂ test were mainly improved within group 1 followed by groups 3 and 2. CONCLUSION： The results of this pilot study demonstrate beneficial effects of hydrotherapy. The study design is feasible. For statistically significant evidence and a robust conclusion of efficacy of Kneipp＇s hydrotherapy, a larger sample size is necessary. TRIAL REGISTRATION NUMBER： NCT 00950326.

Mesenchymal Stem Cell Allograft Improved Pain Management in Dogs with Osteoarthritis

Background: Osteoarthritis is one of the most common bone diseases, triggered by bone destruction stemming from the inflammatory response of chondrocytes. The disease progresses slowly, but halting its progression or finding a cure remains elusive. The treatment of pain associated with osteoarthritis has yielded unsatisfactory results. In recent years, mesenchymal stem cells (MSCs) have emerged as a potential avenue for addressing the condition. In this study, we used MSCs to treat companion dogs with osteoarthritis. Methods: For this study, 26 animals were included in this study to assess the pain and mobility one month after treatment. The pain scores were obtained from owners using a questionnaire based on the Helsinki Chronic Pain Index, and the Liverpool Osteoarthritis in Dogs (LOAD) Owner questionnaire to assess the mobility of the dogs from stem cell infusion. Results: Questionnaires were administered to dog owners before and one month after treatment, and we found that dogs treated with MSCS experienced an 81.2% ± 6.8% reduction in pain and a 77.9% ± 10.1% increase in mobility, whereas most of the dogs in the untreated control group experienced disease progression. Conclusions: The transplantation of stem cells into companion pets is a promising and expanding opportunity for pet owners with aging and arthritic dogs. MSCs may play an important role in the treatment of OA without complications in companion pets.

Clinical effect of scraping therapy in the treatment of knee osteoarthritis

Objective:The objective of this study is to investigate the effect of scraping therapy in the treatment of knee osteoarthritis.Materials and Methods:A total of eighty patients with knee osteoarthritis were assigned to the moxibustion group and the scraping therapy group according to the random numerical table method,with forty cases in each group.Patients in both two groups received functional exercise and moxibustion therapy,and those in the scraping therapy group were supplemented with scraping therapy.The serum indexes of interleukin‑1(IL‑1),IL‑6,tumor necrosis factor‑alpha(TNF‑α),and superoxide dismutase(SOD)were detected before and after the treatment.The clinical syndrome integral and Visual Analog Scale(VAS)on pain of patients were assessed.The clinical therapeutic efficacy was evaluated and compared between the two groups.Results:Patients in the scraping therapy group received better outcomes of serum IL‑1,IL‑6,TNF‑α,and SOD compared with those in the moxibustion group at 2 months after treatment(P<0.05).The scores of clinical syndrome integral and VAS on pain were decreased in two groups at 2 months after the treatment and were lower in the scraping therapy group than those in the moxibustion group(P<0.05).The overall effective rate in the scraping therapy group was higher than that in the control group(87.50%vs.67.50%,P<0.05).Conclusion:The scraping therapy is potentially effective to ameliorate the clinical symptom and pain degree of patients with knee osteoarthritis.

Application of five-element music therapy in pain coping skills training in patients with knee osteoarthritis

Objective:The objective of this study is to assess the application effect of five elements music therapy introduced in the pain coping skills training of knee osteoarthritis(KOA).Materials and Methods:Totally,80 patients with KOA were selected and randomly divided into the experimental group(39 cases)and the control group(41 cases).The control group was only given routine nursing measures,and the experimental group was additionally treated with five-element music therapy on the basis of the control group,twice a day,28 days in total.The Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)was used to evaluate the functional status of the knee joint of the two groups.The clinical efficacy of the two groups was evaluated by Guiding Principles for Clinical Research of New Chinese Medicine in the Treatment of Osteoarthritis.Results:WOMAC score statistically significantly decreased in the experimental group(35.92±9.48 vs.16.17±5.43,P<0.01)and the control group(36.73±6.42 vs.22.53±7.51,P<0.01)after 28 days of intervention when compared with that before intervention;WOMAC score in the experimental group was lower than that of the control group after 28 days of intervention(16.17±5.43 vs.22.53±7.51,P<0.01).The total effective rate of the experimental group was statistically higher than that of the control group(82.0%vs.51.2%,χ2=11.97,P=0.003).Conclusion:The combination of five-element music therapy and routine nursing measures has better effect in relieving pain and bad emotions of patients with KOA when compared with routine nursing measures alone.

Cell-based therapy for management of osteoarthritis

Osteoarthritis(OA)is a most common form of degenerative joint disease,primarily characterized by the degradation of articular cartilage,subchondral sclerosis and inflammation of the synovial membrane.Mesenchymal stem cells(MSCs),a multipotent adult stem cell population,can be isolated from many connective tissue lineages,including those of the diarthrodial joint.Joint-resident MSCs or MSC-like progenitor cells contribute to the maintenance of healthy microenvironment or to the response to trauma.The onset of degenerative changes in the joint related to abnormal condition or depletion of these endogenous MSCs and native host hyaline cartilage cells,leading to limited selfrepair potential of the joint and advance of the degradation.To date,no acknowledged medical treatment strategies,including non-operative and classical surgical techniques,are efficient in restoring normal anatomy and function of hyaline cartilage in OA.This highlights an urgent need for better celled-based therapeutic strategies that supplement these functional cel s exogenously to recover the tissue homeostasis and repair in joint cavity via chondrogenic and anti-in fl ammatory functions.In this review we focus on the role of native MSCs in healthy or OA joint and recent progress in cel-based researches utilizing culture-expanded chondrocytes,pluripotent stem cel s,or MSCs from different sources for treating OA.

Clinical effect of extracorporeal shockwave therapy for knee osteoarthritis: A meta analysis

Objective:To provide evidence-based evidence for the clinical use of shockwave therapy in KOA.Methods: Two researchers independently searched the randomized controlled study of shockwave therapy for KOA in the databases of CNKI、VIP、WanFang Data、 Sinomed and PubMed. Jadad rating scale was used for literature quality evaluation, and the extracted data was meta-analyzed by RevMan5.3 software.Results: A total of 15 randomized controlled trials involving 1248 patients were included. The results of meta-analysis showed: The clinical effective rate of shock wave therapy for knee osteoarthritis was reliable[RR=1.12, 95%CI(1.03, 1.20), p=0.005], and the efficacy was reliable in reducing the visual analogue scale [MD=-1.73, 95%CI(-2.31, -1.14), p<0.00001] , Lequesne osteoarthritis severity index[MD=-1.60, 95%CI(-2.55, -0.64), p<0.00001] and WOMAC[MD=-6.03, 95%CI(-9.49,-2.57) p=0.0006] of KOA patients, without serious adverse reactions.Conclusion:At present, the evidence shows that shock wave can effectively improve the pain and other related symptoms in KOA patients, and the curative effect is reliable.

Photobiomodulation therapy for osteoarthritis: Mechanisms of action

Photobiomodulation(PBM)is a non-invasive therapeutic modality with demonstrated effects in many fields related to regenerative medicine.In the field of orthopedics,in particular,PBM at various wavelengths has demonstrated the capacity to trigger multiple biological effects associated with protective mechanisms in musculoskeletal tissues.The articles cited in this review show that devices operating close to or within the near infrared range at low intensities can provoke responses which favor the shift in the predominant catabolic microenvironment typically seen in degenerative joint diseases,especially osteoarthritis(OA).These responses include proliferation,differentiation and expression of proteins associated with stable cell cycles.Additionally,PBM can also modulate oxidative stress,inflammation and pain by exerting regulatory effects on immune cells and blocking the transmission of pain through sensory neuron fibers,without adverse events.Collectively,these effects are essential in order to control the progression of OA,which is in part attributed to exacerbated inflammation and degradative enzymatic reactions which gradually contribute to the destruction of joint tissues.PBM may offer medical experts ease of application,financial viability,efficacy and lack of serious adverse events.Therefore,it may prove to be a suitable ally in the management of mild to moderate degrees of OA.This review explores and discusses the principal biological mechanisms of PBM and how the produced effects may contribute to the amelioration of osteoarthritic progression.Literature was reviewed using PubMed and Google Scholar in order to find studies describing the mechanisms of PBM.The investigation included a combination of nomenclature such as:“photobiomodulation”,“phototherapy”,“laser therapy”,“PBM”,“osteoarthritis”,low level light therapy”,“inflammation”and“cartilage”.We considered only articles written in English,with access to the full text.

Systematic evaluation and Meta-analysis of acupuncture and collaterals cupping therapy for Knee Osteoarthritis

Objective:In order to obtain the best treatment program for Knee Osteoarthritis(KOA),to alleviate the pain of patients with KOA,and to systematically evaluate the efficacy of acupuncture cupping therapy for KOA.Methods:we used computer to search the databases of CNKI(1989-2018.10),Wanfang(1989-2018.10),VIP(1989-2018.10),PubMed(1966-2018.10),EMbase(1986-2018.10)and Cochrane Library(the 3rd issue of 2018).And the literature quality was evaluated by Jadad scale.Results:A total of 19 eligible RCT studies were included,and a total of 2,088 patients participated in the eligible clinical study.Meta-analysis results showed that the total effective rate OR combination=2.85[OR=3.98,95%CI(2.98,5.32),P<0.00001].The results showed that the curative effect of acupuncture and collaterals cupping in the treatment of KOA was superior to other therapies.Conclusion:Acupuncture and cupping therapy of traditional Chinese medicine is effective and safe in treating KOA.Due to the impact of the original study on Meta-analysis results,more large samples and high-quality clinical trials are still needed to verify.

Microenvironment-responsive nanosystems for osteoarthritis therapy

Osteoarthritis(OA)represents an enduring and widespread global burden,causing significant morbidity and disability,whose pathology is characterized by persistent inflammation,progressive cartilage degeneration,ab-normal bone homeostasis,and excessive synovial hyperplasia,resulting from its complex microenvironment.Unfortunately,current therapeutic approaches for OA remain suboptimal,prompting increased interest in ad-vanced nanotechnology as a means to enhance therapeutic effects.In recent years,significant progress has been made in the development of versatile nanoplatforms designed to the specific microenvironment of OA,resulting in promising results and introducing the concept of“OA nanomedicine”.Compared to the conventional therapies like non-steroidal anti-inflammatory drugs(NSAIDs),OA nanomedicine offers precise targeted,controllable and personalized ways for OA therapy,contributing to better outcomes.However,a comprehensive review consoli-dating the“OA nanomedicine”is currently absent from literature.Therefore,in this review,we aim to unravel the key pathological and microenvironmental characteristics of OA while summarizing the properties and advantages of nanosystems possessing microenvironment-reprogramming capabilities for OA therapy.First,we make a retro-spection of the features of OA pathology and OA microenvironment.Furthermore,we provide an overview of the advances in OA nanomedicine.Eventually,we discuss the present challenges associated with OA nanomedicine and provide insights into its future prospects from a clinical-translational lens.By doing so,this review can foster and propel the successful development of OA nanomedicine,addressing the unmet needs in OA therapy.

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:PubM ed,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,welltolerated,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.

Effectiveness of Maitland and Mulligan mobilization methods for adults with knee osteoarthritis:A systematic review and metaanalysis

BACKGROUND As a serious global problem,knee osteoarthritis(KOA)often leads to pain and disability.Manual therapy is widely used as a kind of physical treatment for KOA.AIM To explore further the efficacy of Maitland and Mulligan mobilization methods for adults with KOA.METHODS We searched PubMed,the Cochrane Library,EMbase,Web of Science and Google Scholar from inception to September 20,2020 to collect studies comparing Maitland and Mulligan mobilization methods in adults with KOA.The quality of the studies was assessed using the Physiotherapy Evidence Database Scale for randomized controlled trials.Data analyses were performed using Review Manager 5.0 software.RESULTS A total of 341 articles were screened from five electronic databases(PubMed,the Cochrane Library,EMbase,Web of Science and Google Scholar)after excluding duplicates.Ultimately,eight trials involving 471 subjects were included in present systematic review and meta-analysis.The mean PEDro scale score was 6.6.Mulligan mobilization was more effective in alleviating pain[standardized mean difference(SMD)=0.60;95%confidence interval(CI):0.17 to 1.03,P=0.007;I2=60%,P=0.020]and improving Western Ontario and McMaster Universities function score(SMD=7.41;95%CI:2.36 to 12.47,P=0.004;I2=92%,P=0.000).There was no difference in the effect of the two kinds of mobilization on improving the range of motion(SMD=9.63;95%CI:-1.23 to 20.48,P=0.080;I2=97%,P=0.000).CONCLUSION Mulligan mobilization technique is a promising intervention in alleviating pain and improving function score in KOA patients.

Efficacy of therapeutic ultrasound vs sham ultrasound on pain and physical function in people with knee osteoarthritis: A meta-analysis of randomized controlled trials

AIM: To determine the efficacy of therapeutic ultrasound vs sham for improving pain and physical function immediately post-intervention in people with knee osteoarthritis(OA). METHODS: We hand searched meta-analyses on the topic published in 2010 and updated the search in three electronic databases(MEDLINE, EMBASE, CINAHL) January 1, 2009 to September 5, 2013 to identify relevant studies. The inclusion criteria were human randomized controlled trials published in the English language in which active therapeutic ultrasound was compared tosham ultrasound, data for people with knee OA were reported separately, participants were blinded to treatment allocation and outcomes assessed before and after treatment included pain, self-reported physical function and performance-based physical function. Two reviewers independently screened titles and abstracts retrieved in the search to identify trials suitable for full text review. Data extraction and risk of bias assessment of the identified trials were completed independently by two reviewers. Pooled analyses were conducted using inverse-variance random effects models.RESULTS: We screened 1013 titles and abstracts. Meta-analysis of pain outcomes from 5 small trials(281 participants/OA knees) showed that, compared to sham ultrasound, therapeutic ultrasound improves pain [standardized mean difference(SMD)(95%CI) =-0.39(-0.70--0.08); P = 0.01] but not physical function [self-reported in 3 trials(130 participants/OA knees): SMD(95%CI) =-0.21(-0.55-0.14), P = 0.24; walking performance in 4 trials(130 participants/OA knees): SMD(95%CI) =-0.11(-0.59-0.37), P = 0.65). For the walking performance outcome, the dispersion of the estimated effects exceeded that expected due to sampling error(χ2 = 8.37, P = 0.04, I 2 = 64%). Subgroup analyses of three trials that administered high dose ultrasound improved the consistency(I2 = 28%) but the treatment effect remained insignificant.CONCLUSION: Meta-analyzed double-blind placebocontrolled randomized trials provide low-strength evidence that therapeutic ultrasound decreases knee OA pain and very low-strength evidence that it does not improve physical function.

Efficacy of Slow Reversal Hold and Isometrics in Improving Muscle Strength, Increasing Range of Motion, and Reducing Pain in Patients with Osteoarthritis of Knee

Osteoarthritis of knee is a common problem in the elderly population worldwide. Physical therapy has been shown to be useful in decreasing pain and increasing mobility in this population. The aim of this study was to study the effectiveness of slow reversal hold and isometric exercise techniques in reducing pain, increasing muscle strength, and increasing range of motion for knee flexion in patients with osteoarthritis of knee. The other aim of this study was to compare the relative effectiveness of these two interventions. 60 subjects participated in this study and were randomly assigned either to the slow reversal hold group (n = 30) or, to the isometrics exercise group (n = 30). All subjects performed their respective exercises for 3 weeks. Pain scores using the visual analog scale, muscle strength using manual muscle testing of quadriceps and hamstrings, and range of motion (ROM) for knee flexion using a goniometer were recorded both pre-treatment and post-treatment for both left and right knees. Both the interventions showed a significant decrease in pain scores, an increase in muscle strength, as well as an increase in the ROM. However, ROM was significantly increased in the slow reversal hold group as compared to the isometrics group in both knees. It was concluded that both exercise techniques could be useful in patients with osteoarthritis of knee for decreasing pain and increasing muscle strength. Slow reversal hold technique might be a better technique than isometrics for increasing ROM for knee flexion.