Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Adipose-derived regenerative therapies for the treatment of knee osteoarthritis

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.

Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.

Acupotomy ameliorates knee osteoarthritis-related collagen deposition and fibrosis in rabbit skeletal muscle through the TGF-β/Smad pathway

Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

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.

Knee Osteoarthritis Progression after Distal Femur Closing Wedge Osteotomy

Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to identify the factors associated with the progression of knee osteoarthritis after a medial closing-wedge distal femoral osteotomy. Methods: Hospital-based observational study on 20 patients who underwent a medial closing-wedge distal femoral osteotomy evaluating the progression of osteoarthritis using the Kellgren and Laurence classification. The Wilcoxon test was used to compare the variation in the progressive stage of the Kellgren and Laurence classification of knee osteoarthritis preoperatively and at the final follow up. Univariate analysis made it possible to determine the factors associated with progression. The final significance threshold for statistical tests was set at 5% (p Results: Overall, the mean follow-up of 46 months ± 6.6 months, with a mean age of 43 years (range: 27 - 69 years) and a female predominance (M: F = 3/7). The progression of tibiofemoral osteoarthritis following a medial closing-wedge distal femoral osteotomy is associated with valgus or varum malalignment been a moderate valgus (OR 6.2 [1.5 - 42.7] at 95% CI;p-value = 0.02), a correction of the mechanical deviation angle with a valgus alignment (OR 2.7 [0.9 - 8.3] at 95% CI), and loss of correction (OR 3.8 [1.3 - 11.6] at 95% CI;p -value) for the lateral compartment while varus alignment (OR 1.7 [0.9 - 8.3] 95% CI, p-value = 0.05) and with rupture of the lateral cortex (OR 2.8 [1.7 - 11.5] 95% CI, p-value = 0.02) were those of the medial compartment. Conclusion: Distal femur closing wedge osteotomy does not definitively interrupt the progression of valgus knee osteoarthritis. The factors associated with the progression of this pathology are modifiable. Taking them into account when performing this surgical technique could improve the osteotomy survival curve.

Adipose-derived stem cells and knee osteoarthritis:New perspectives,old concerns

In this editorial,we comment on the paper by Muthu et al published in the recent issue of the journal.This editorial review focusses on the use of adipose-derived stem cells(ADSCs)in knee osteoarthritis treatment.We discuss the differences between the stromal vascular fraction and microfragmented adipose tissue and highlight the results of clinical studies comparing both treatments and the use of hyaluronic acid,platelet-rich plasma,and bone marrow aspirate concentrate.The use of expanded ADSCs is also discussed;moreover,concerns regarding treatment with ADSCs,particularly the heterogeneity of published studies and the need to standardize protocols to explore clinical potential is explored.

Autologous peripheral blood-derived orthobiologics:Different types and their effectiveness in managing knee osteoarthritis

Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

Study on compound Duzhong Jiangu granule in the treatment of knee osteoarthritis based on transcriptome analysis strategy

Duzhong Jiangu Granule in the treatment of primary osteoarthritis(POA)model of postmenopausal kidney deficiency type in Hartley female guinea pigs after ovariectomy,and the correlation between gene expression of bone marrow tissue,cartilage tissue,and knee osteoarthritis.Methods:383-months-old Hartley female guinea pigs after one week of adaptive feeding were weighed about 400 g±20 g,numbered,and sorted by ear tag.Six of them were selected as normal groups by looking up random number tables.The remainder were removed from the bilateral ovaries to construct the postmenopausal kidney deficiency model,and castrated guinea pigs were used to construct the postmenopausal kidney deficiency POA model.After the modeling cycle,a guinea pig from the blank group and a guinea pig from the model group were sacrificed and the right knee was observed.The model was established and the experiments continued.There were five guinea pigs in the blank group,and the remaining model guinea pigs were randomly divided into model control group,high-dose group of compound Duzhong Jiangu granules,middle-dose group of compound Duzhong Jiangu granules,low-dose group of compound Duzhong Jiangu granules and design group,with 5 guinea pigs in each group.Blanks and model groups were given a cellulose sodium solution by gavage.The guinea pigs were sacrificed after 30 days of intragastric administration.The left knee cartilage and bone marrow of the blank group,model group,middle dose group,and high dose group of compound Duzhong Jiangu granule were collected and applied to transcriptome sequencing,and the sequencing data were analyzed,including differential gene expression analysis,functional enrichment analysis of database established by Gene Ontology federation(GO)and Kyoto Encyclopedia of Gene and Genome(KEGG)pathway enrichment analysis.The complete specimens of the right knee joint were collected,and the morphological changes of the cartilage of the right knee joint in each group were observed by saffron rapid green staining,and the subchondral bone was quantitatively analyzed by Micro CT so that the expression of TRAF6,MIP-1βand IL-1βprotein in NF-kappa B signaling pathway was detected by Western Blot technique(WB).Results:The results of Safranin Fast Green staining showed that Compound Duzhong Jiangu Granules could effectively reduce the degree of morphological damage of articular cartilage in guinea pigs with the POA model.According to the analysis results of the subchondral bone structure under Micro CT,Compound Duzhong Jiangu Granules can improve the bone condition of the POA model,thus delaying the process of degenerative changes of the knee joint.From the results of transcriptome analysis,Compound Duzhong Jiangu Granules can inhibit the expression of related genes in POA model guinea pigs.According to the results of Wester Bolt verification,Compound Duzhong Jiangu Granules can effectively improve knee osteoarthritis.Conclusions:The effect of Compound Duzhong Jiangu Granules on OA is obvious,and its mechanism may be related to the expression of genes GZMK,Jchain,igkc,IGHV3-74,IGHV3-11,IGHV4-1,CCL5,and IGKV1–39.

Research Progress in Traditional Chinese Medicine Treatment of Knee Osteoarthritis

Knee osteoarthritis(KOA)is a degenerative disease characterized by pathological changes in the cartilage and subchondral bone of the knee joint.Initially,knee joint pain is the main symptom,and in the later stages,deformities and mobility disorders may occur.Modern medicine lacks effective treatment methods for early and mid stage KOA,and has drawbacks such as significant side effects and high costs.A large number of stud‐ies have confirmed that traditional Chinese medicine has unique advantages in treating KOA,and has obvious advantages such as small trauma,low cost,and definite therapeu‐tic effect,which are gradually being accepted by a large number of KOA patients.The commonly used methods for preventing and treating KOA with traditional Chinese medicine in clinical practice include:oral administration of traditional Chinese medi‐cine,external application of traditional Chinese medicine,fumigation,acupuncture therapy,massage therapy for regulating tendons,and targeted penetration therapy of tra‐ditional Chinese medicine.According to relevant literature,traditional Chinese medicine can significantly alleviate knee joint symptoms and improve knee joint function in patients with knee osteoarthritis,which is of great significance for the prevention and treatment of knee osteoarthritis.This article provides a review of the research progress in the prevention and treatment of KOA using traditional Chinese medicine in recent years.

Clinical efficacy of Xibitong recipe combined with platelet-rich plasma in the treatment of moderate knee osteoarthritis

Objective:To observe the clinical effect of knee-bitong prescription combined with platelet-rich plasma in the treatment of knee osteoarthritis in the middle stage.Methods:From May 2018 to January 2019,90 patients with moderate knee osteoarthritis(K-L classificationⅡandⅢ)with liver and kidney deficiency were admitted,and 45 patients were divided into experimental group and control group.The test group included 15 males and 30 females;aged 46 to 70(58.93±10.671)years;course of disease was 1 to 8 years(27.06±4.216)months;K-L classification:33 cases in gradeⅡand 12 cases in gradeⅢ.Jibitongfang Jianjian Granules is taken orally once a day,once in the morning and evening,14 days a course of treatment,and combined with platelet-rich plasma(2ml)articular cavity injection,once every 14 days,a total of two,14 days apart;control group male 12 There were 33 females aged 43-68(57.00±8.832)years old;the course of disease was 1-8 years(25.40±3.718)months;KL classification:36 cases of gradeⅡ,9 cases of gradeⅢ,and the control group were given platelet-rich plasma(2ml)Injection into the joint cavity,the treatment course and frequency are the same as the experimental group.Record and compare the VAS score,WOMAC score,matrix metalloproteinase-1 and interleukin-1βlevels of joint fluid before and after treatment for one month to evaluate the therapeutic effect.Results:All 90 cases were followed up without serious adverse reactions or other complications.The WOMAC scores of the experimental group and the control group before and after treatment were:106.40±47.962,116.13±41.151,55.13±22.022,62.67±26.232.The VAS scores of the two groups before and after treatment were:5.87±2.446,5.80±2.145,2.67±1.345,4.00±1.964.The levels of interleukin 1βin the test group and the control group before and after treatment were:78.33±7.227,76.60±7.069,25.73±3.239,31.13±5.743.The levels of matrix metalloproteinase-1 before and after treatment in the two groups were:2299.66±179.343,2206.66±194.235,1741.86±183.077,1762.46±192.097.Conclusion:The combination of platelet-rich plasma and knee-bitong decoction in the treatment of moderate knee osteoarthritis is better than platelet-rich plasma group in relieving knee pain,improving knee function and reducing the levels of interleukin-1βand matrix metalloproteinase-1 in joint fluid.And the side effects are small,it is worth clinical application.

There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and function.Determining the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and rehabilitation.This systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders.Methods:Five databases(MEDLINE,Embase,CINAHL,SPORTDiscus,and Web of Science)were searched from inception to September 2022.Only studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were included.Meta-analyses for each knee disorder were performed.Outcome-level certainty was assessed using the Grading of Recommendations Assessment,Development,and Evaluation,and evidence gap maps were created.Results:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were included.Individuals with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(SMD)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(SMD=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(SMD=-0.48,95%CI:-0.82 to-0.14),concentric(SMD=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(SMD=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar tendinopathy.Individuals with PFP presented with reduced hamstring flexibility when compared to pain-free controls(SMD=-0.76,95%CI:-1.15 to-0.36).Evidence gap maps identified insufficient evidence for chondromalacia patellae and hamstring morphology across all gradual-onset knee disorders.Conclusion:Our findings suggest that assessing and targeting impairments in hamstring strength and flexibility during rehabilitation may be recommended for individuals with knee OA or PFP.

Cytokines as biochemical markers for knee osteoarthritis

Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.

State-of-the-Art management of knee osteoarthritis

Osteoarthritis(OA) is the most common type of arthritis found in the United States' population and is also the most common disease of joints in adults throughout the world with the knee being the most frequently affected of all joints. As the United States' population ages along with the increasing trends in obesity prevalence in other parts of the world, it is expected that the burden of OA on the population, healthcare system, and overall economy will continue to increase in the future without making major improvements in managing knee OA. Numerous therapies aim to reduce symptoms of knee OA and continued research has helped to further understand the complex pathophysiology of its disease mechanism attempting to uncover new potential targets for the treatment of OA. This review article seeks to evaluate the current practices for managing knee OA and discusses emerging therapies on the horizon. These practices include non-pharmacological treatments such as providing patient education and self-management strategies, advising weight loss, strengthening programs, and addressing biomechanical issues with bracing or foot orthoses. Oral analgesics and anti-inflammatories are pharmacologicals that are commonly used and the literature overall supports that some of these medications can be helpful for managing knee OA in the short-term but are less effective for long-term management. Additionally, more prolonged use significantly increases the risk of serious associated side effects that are not too uncommon. Diseasemodifying osteoarthritis drugs are being researched as a treatment modality to potentially halt or slow disease progression but data at this time is limited and continued studies are being conducted to further investigate their effectiveness. Intra-articular injectables are also implemented to manage knee OA ranging from corticosteroids to hyaluronans to more recently plateletrich plasma and even stem cells while several other injection therapies are presently being studied. The goal of developing new treatment strategies for knee OA is to prolong the need for total knee arthroplasty which should be utilized only if other strategies have failed. High tibial osteotomy and unicompartmental knee arthroplasty are potential alternatives if only a single compartment is involved with more data supporting unicompartmental knee arthroplasty as a good treatment option in this scenario. Arthroscopy has been commonly used for many years to treat knee OA to address degenerative articular cartilage and menisci, however, several high-quality studies have shown that it is not a very effective treatment for the majority of cases and should generally not be considered when managing knee OA. Improving the management of knee OA requires a multi-faceted treatment approach along with continuing to broaden our understanding of this complex disease so that therapeutic advancements can continue to be developed with the goal of preventing further disease progression and even potentially reversing the degenerative process.

Intraarticular injections(corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis

Osteoarthritis(OA)is a complex"whole joint"disease pursued by inflammatory mediators,rather than purely a process of"wear and tear".Besides cartilage degradation,synovitis,subchondral bone remodeling,degeneration of ligaments and menisci,and hypertrophy of the joint capsule take parts in the pathogenesis.Pain is the hallmark symptom of OA,but the extent to which structural pathology in OA contributes to the pain experience is still not well known.For the knee OA,intraarticular(IA)injection(corticosteroids,viscosupplements,blood-derived products)is preferred as the last nonoperative modality,if the other conservative treatment modalities are ineffective.IA corticosteroid injections provide short term reduction in OA pain and can be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with OA.IA hyaluronic acid(HA)injections might have efficacy and might provide pain reduction in mild OA of knee up to 24 wk.But for HA injections,the costeffectiveness is an important concern that patients must be informed about the efficacy of these preparations.Although more high-quality evidence is needed,recent studies indicate that IA platelet rich plasma injections are promising for relieving pain,improving knee function and quality of life,especially in younger patients,and in mild OA cases.The current literature and our experience indicate that IA injections are safe and have positive effects for patient satisfaction.But,there is no data that any of the IA injections will cause osteophytes to regress or cartilage and meniscus to regenerate in patients with substantial and irreversible bone and cartilage damage.

Comparison of intra-articular injection of parecoxib vs oral administration of celecoxib for the clinical efficacy in the treatment of early knee osteoarthritis

BACKGROUND Non-steroid anti-inflammatory drugs(NSAIDs)have played a crucial role in the treatment of osteoarthritis,especially in the early stages.However,the cardiovascular risk and adverse gastrointestinal reactions of oral NSAIDs in elderly people cannot be underestimated.Intra-articular injection of NSAIDs may be a new attempt for early knee osteoarthritis treatment.Parecoxib may be a suitable drug for intra-articular injection.AIM To observe the clinical efficacy of the intra-articular injection of parecoxib for early knee osteoarthritis.METHODS Early knee osteoarthritis patients(n=110)were retrospectively analyzed.These patients were divided into three groups:Basic treatment+oral glucosamine(group A,n=37),oral celecoxib+basic treatment+oral glucosamine(group B,n=37),and intra-articular injection of parecoxib+basic treatment+oral glucosamine(group C,n=36).Intra-articular injection of parecoxib was performed once every 2 wk at a dose of 40 mg each time,for three times total.The three groups were compared in terms of visual analogue scale(VAS)scores,Hospital for Special Surgery(HSS)scores and patient satisfaction before and after treatment.The levels of inflammatory cytokines in the synovial fluid were detected in the three groups before and after treatment.RESULTS All patients were followed up for an average of 15.5±2.7 mo.The clinical efficacy was estimated by VAS and HSS scores at 12 mo after treatment.Inflammatory cytokine levels in the synovial fluid were evaluated at 3 mo after treatment.VAS and HSS scores were significantly improved in each group compared with before(P<0.001).There were significant differences among the three groups in VAS and HSS scores(P<0.001).The clinical efficacy of group C was superior to that of groups A and B(P<0.001),while group B outperformed group A in this respect(P<0.001).The patient satisfaction was the highest in group C(P<0.001).After treatment,the levels of tumor necrosis factorα(TNF-α)and interleukin(IL)-6 in the synovial fluid decreased in each group compared with before(P<0.001),while the levels of IL-10 increased(P<0.001).The three groups differed significantly in the levels of TNF-a,IL-6 and IL-10 in the synovial fluid after treatment(P<0.001).CONCLUSION For patients with early knee osteoarthritis,intra-articular injection of parecoxib could effectively improve clinical symptoms.This method may be a reliable alternative for early knee osteoarthritis.

Effects of resistance and Tai Ji training on mobility and symptoms in knee osteoarthritis patients

Background:No studies have compared effectiveness of resistance training and Tai Ji exercise on relieving symptoms of knee osteoarthritis(OA).The purpose of the study was to evaluate effects of a 10-week Tai Ji and resistance training intervention on improving OA symptoms and mobility in seniors with knee OA.Methods:Thirty-one seniors(60-85 years)were randomly assigned to a Tai Ji program(n=12),a resistance training program(n=13),and a control group(n=6).All participants completed the Western Ontario and McMaster(WOMAC)Osteoarthritis Index and performed three physical performance tests(6-min walk,timed-up-and-go,and timed stair climb and descent)before and after the 10-week intervention.Results:The participants in the resistance training group significantly improved on the timed-up-and-go test(p【0.001),the WOMAC pain subscore(p=0.006),WOMAC stiffness sub-score(p【0.001),and WOMAC physical function sub-score(p=0.011).The Tai Ji group significantly improved on the timed-up-and-go test(p【0.001),but not on the WOMAC scores.Conclusion:Resistance training was effective for improving mobility and improving the symptoms of knee OA.Tai Ji was also effective for improving mobility,but did not improve knee OA symptoms.

Outcomes of mobile bearing unicompartmental knee arthroplasty in medial osteoarthritis knee with and without preoperative genu recurvatum

AIM To compare clinical outcomes of patients with and without preoperative genu recurvatum(GR) following mobile bearing unicompartmental knee arthroplasty(UKA). METHODS We prospectively followed 176 patients for at least 24 mo who had been treated by unilateral, minimally invasive, Oxford UKA. Patients with medial osteoarthritis(OA) knee and preoperative GR(Group Ⅰ) accounted for 18%(n = 32) and patients without preoperative GR(Group Ⅱ) accounted for the remaining 82%(n = 144). Knee score, pain scores, and functional scores were assessed for each patient and compared between the two groups. The incidence of postoperative GRand the postoperative hyperextension angles also were recorded and analyzed. RESULTS The pain score, knee score and functional score were not significantly different between the two groups. Similarly, the incidence of postoperative GR and the measured hyperextension angles were not significantly different between the two groups. The incidence of postoperative GR was 1/32(3.12%) in Group Ⅰ and 1/144(0.69%) in Group Ⅱ(P = 0.34). The mean postoperative hyperextension angles were 2.40°± 2.19°(range: 1°-7°) for Group Ⅰ and 1.57°± 3.51°(range: 1°-6°) for Group Ⅱ(P = 0.65).CONCLUSION Medial OA of the knee and concomitant GR is not a contraindication for the mobile bearing UKA.

T1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis

AIM To investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.METHODS Magnetic resonance(MR) images were acquired from5 subjects scheduled for total knee arthroplasty(TKA)(mean age 70 years) and 20 young healthy control subjects without knee pain(mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained.Following TKA each condyle was divided into 4 parts(distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens(bone and cartilage blocks) were examined. For each joint,the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system.In magnetic resonance imaging(MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.RESULTS Eleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis(OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle, P = 0.461;medial posterior condyle(MPC), P = 0.352; lateral distal condyle, P = 0.654; lateral posterior condyle, P = 0.550],suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage.Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA(P= 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients. CONCLUSION Though cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.