Therapy For Knee Osteoarthritis Research Articles

Scraping therapy for knee osteoarthritis: a systematic review and Meta-analysis.

To systematically evaluate the efficacy of scraping therapy on knee osteoarthritis (KOA). A computerized search was conducted in several databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wanfang, and Chinese BioMedical Literature Database, from the establishment date of these databases to April 9, 2023. Randomized controlled trials (RCTs) on scraping therapy for KOA were collected in accordance with the "Participants-Intervention-Control-Outcome-Study design" criteria. The methodological evaluation of the included studies was carried out using RoB 2.0, and Meta-analysis was conducted using RevMan. The Grades of Recommendations Assessment, Development and Evaluation (GRADE System) was applied to grade the quality of evidence. A total of 12 RCTs with 997 subjects were included in the Meta-analysis. Results indicated that compared with the control group, the scraping therapy treatment group exhibited increased Lysholm scores [mean difference (MD) = 4.96, 95% confidence intervals (CI) (3.18, 6.74), P < 0.000 01] and Hospital for Special Surgery scores [MD= 8.35, 95% CI(3.92, 12.78), P =0.0002] and decreased visual analog scale scores [MD = -2.11, 95% CI(-3.79, -0.44), P =0.01] and Western Ontario and McMaster University Osteoarthritis Index scores [MD= -6.77, 95% CI(-8.99, -4.56), P < 0.000 01)]. The quality of evidence obtained in this Meta-analysis was low according to the GRADE system. The available evidence suggests that scraping therapy may have certain clinical efficacy in the treatment of KOA. However, further high-quality RCTs are needed to confirm the findings.

Efficacy and safety of platelet-rich plasma and hyaluronic acid combination therapy for knee osteoarthritis: a systematic review and meta-analysis.

This study aimedto evaluate whether a combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) is more effective and safer than injection alone for treating KOA. MEDLINE (PubMed), the Cochrane Library, EMBASE, and Web of Science databases were systematically searched for articles published until January 2024, and gray literature and bibliographic references were searched. All published randomized controlled trials (RCTs) compared pain, functional outcomes, and adverse events (AEs) associated with PRP + HA therapy vs. PRP or HA treatments. Two independent researchers extracted the pertinent data and evaluated the methodological quality following the PRISMA guidelines. The primary outcomes were pain, functional outcomes, and AEs. A fixed-effects model was used for data analysis in cases with low heterogeneity (P > 0.10 and I2 < 50%). Otherwise, a random effects model was used. Ten RCTs involving 943 patients were included in the analysis. The statistical findings did not differ between the treatment of PRP + HA and PRP alone, while a discernible enhancement in treatment efficacy was observed when compared to HA monotherapy: the visual analog scale scores at 1- (mean difference[MD], -1.00; 95% CI: -1.37 - -0.62; P < .001), 6- (MD, -1.87; 95% CI: -3.46 - -0.28; P = .02), 12-months (MD, -2.07; 95% CI: -3.77 - -0.38; P = .02), and the Western Ontario and McMaster Universities Arthritis Index total scores at 12-months (MD, -8.82; 95% CI: -14.48 - -3.16; P = .002). The incidence of adverse events was notably lower with PRP + HA than with HA alone (OR, 0.37; 95% CI: 0.19 - 0.69; P = .00) or PRP alone (OR, 0.51; 95% CI, 0.30 - 0.87; P = .01). PRP + HA therapy resulted in more pronounced pain and functional improvement in symptomatic KOA patients than HA treatments, and combination therapy may have higher clinical safety than PRP or HA monotherapy.

Exosomes derived from 3D-cultured MSCs alleviate knee osteoarthritis by promoting M2 macrophage polarization through miR-365a-5p and inhibiting TLR2/Myd88/NF-κB pathway

Exosomes (EXO) derived from mesenchymal stem cells (MSCs) are recently shown to have therapeutic effects in preclinical models of knee osteoarthritis (KOA). However, their potential for conversion into a clinical therapy are limited by several shortcomings such as low yield and suboptimal efficacy. This study developed 3D-EXO to improve exosome yield and efficacy through 3D-culturing of MSCs, with the aim of achieving overall better therapeutic effects compared to traditional 2D-cultured MSC-derived EXO (2D-EXO). In a rat KOA model, 3D-EXO led to better preservation of bone structure and protection from cartilage damage compared to 2D-EXO. Interestingly, in vitro experiments showed no significant differences between 3D-EXO and 2D-EXO in their direct effects on chondrocytes. To explain these findings, we looked into the possible effects of MSC-derived EXO on the immune microenvironment, specifically in modulating phenotypic expression in macrophages. In vitro investigations showed that 3D-EXO increased the expression of M2 phenotype markers in macrophages to a greater extent than 2D-EXO. RNA-seq analysis revealed that expression of miR-365a-5p was more upregulated in 3D-EXO than 2D-EXO. Through micro-RNA mimics transfection, we found that miR-365a-5p acted directly on TLR2 mRNA to inhibit TLR2 translation, indicating that 3D-EXO promoted M2 polarization of macrophages by inhibiting the TLR2/Myd88/NF-κB axis. The immunomodulatory effects of 3D-EXO were confirmed by the observation that the metabolic status of chondrocytes was significantly improved after co-culturing with 3D-EXO-treated macrophages. In summary, 3D-EXO can effectively promote M2 macrophage polarization through increased expression of miR-365a-5p, which in turn improves the metabolic state of chondrocytes and resulting in overall better in vivo therapeutic effects on KOA. The findings in this study imply the development of new therapies for KOA based on MSC-derived EXO.

Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits.

To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration. The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3 II/LC3 I were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05). Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA.

Consensus on clinical drug therapy for knee osteoarthritis in China (2023)

Osteoarthritis (OA) is a heterogeneous disease that involves structural alterations in the articular cartilage, synovium, ligaments, subchondral bone, and the surrounding bone tissue. Among the various types of OA, knee osteoarthritis (KOA) is the most prevalent, presenting with symptoms such as joint pain, swelling, stiffness, and functional limitations. And its high disability rate places a significant burden on both individuals and society. Pharmacological intervention plays a crucial role in the comprehensive management of KOA. However, the establishment of standardized treatment protocols for the accurate and appropriate selection of medications for patients remain pressing clinical challenges. The Osteoarthritis Group of the Rheumatology and Immunology Physicians Branch of the Chinese Medical Doctor Association has developed this expert consensus by drawing upon current research findings, relevant guidelines, and consensus statements from both domestic and international sources. This consensus adheres to international standards for consensus development and incorporates input from a diverse panel of experts.The consensus encompasses six aspects: disease prevention, treatment goals, clinical typing, therapeutic drugs, follow-up and evaluation, and medication for comorbid populations. A total of 27 recommendations are put forward, aiming to provide clinicians with guidance for the safe and standardized use of drugs, thereby improving the diagnosis and treatment level of KOA and benefiting patients.

Adjunct treatment with ozone to enhance therapy of knee osteoarthritis: preliminary results.

Knee osteoarthritis (knee OA), commonly known as gonarthrosis, is a chronic pathology involving knee at the joint level causing progressive pain, stiffness and difficulty in ambulation and leg movements. So far in situ infiltration therapies such as platelet rich plasma, conditioned autologous serum or hyaluronic acid, provided some encouraging though limited hopes for a routinely recommended therapy for knee OA. Recent clinical successful observations about the use of whole autologous blood ozonated with a calibrated mixture of oxygen and ozone, has promoted the present research study, in order to treat knee OA. A number of 250 patients suffering with knee OA of different Ahlback scores, were treated with infiltration of ozonated blood and evaluated for their WOMAC and Lequesne indexes, pre- and post-treatment, to evaluate pain, disability and stiffness. Patients recovered about 50% of their health status, reducing pain, stiffness and disability by only 5 sessions, one/week, with 20μg/ml O3 ozonated autologous blood knee infiltrations. The evidence asks for further supporting results yet encourages our efforts to go ahead in this research issue. Key Points •The oxygen-ozone therapy via ozonated blood infiltration was used in this study. •Ozone reduced pain, disability, and stiffness in both female and male patients. •The treatment with ozone improved WOMAC both in type I and type II Ahlback knee OA. •The oxygen-ozone therapy via ozonated blood ameliorated Lequesne functional index.

A novel cell source for therapy of knee osteoarthritis using atelocollagen microsphere-adhered adipose-derived stem cells: Impact of synovial fluid exposure on cell activity

IntroductionAdministration of adipose-derived stem cells (ADSCs) into the joint cavity has been shown to alleviate the symptoms of knee osteoarthritis (OA) by releasing exosomes and anti-inflammatory cytokines. However, the therapeutic effect of these cells is limited by their rapid disappearance after administration. Thus, it is necessary to prolong cell survival in the joint cavity. This study aimed to investigate the potential application of ADSCs adhered to atelocollagen microspheres (AMSs) for cell therapy of knee OA. MethodsADSCs were cultured for 2, 4, and 7 days in AMS suspension or adherent culture dishes. The supernatants were analyzed for IL-10 and exosome secretion via enzyme-linked immunosorbent assay and Nanosight. The effect of AMS was compared with that of adherent-cultured ADSCs (2D-cultured ADSCs) using transcriptome analysis. Moreover, the solubility of AMS and viability of ADSCs were evaluated using synovial fluid (SF) from patients with knee OA. ResultsCompared with 2D-cultured ADSCs, AMS-cultured ADSCs exhibited a significant increase in secretion of exosomes and IL-10, and the expression of several genes involved in extracellular matrix and immune regulation were altered. Furthermore, when AMS-cultured ADSCs were cultured in SF from knee OA patients to mimic the intra-articular environment, the SF dissolved the AMSs and released viable ADSCs. In addition, AMS-cultured ADSCs showed significantly higher long-term cell viability than 2D-cultured ADSCs. ConclusionIncreased survival of AMS-adhered ADSCs was observed in the intra-articular environment, and AMSs were found to gradually dissipate. These results suggest that AMS-adhered ADSCs are promising source for cell therapy of knee OA.

Prognostic Factors in Intra-articular Platelet-Rich Plasma Treatment for Knee Osteoarthritis: A Comparative Analysis of Responders and Nonresponders.

Knee osteoarthritis (KOA) is a chronic joint disease affecting activities of daily living (ADL) and quality of life due to pain and limited range of motion, afflicting a large number of patients worldwide. However, it is difficult to prevent the progression of the disease. Therapeutic strategies for KOA aim to maintain ADL and QOL by alleviating pain or managing locomotive function. Recently, intra-articular injection of platelet-rich plasma (PRP) has been gaining attention. In this study, the clinical results of PRP treatment in our institution were reported and compared between responders and non-responders using patient characteristics and imaging data assessed from plain X-rays and magnetic resonance imaging (MRI). Participants in the study were KOA patients with varus deformity assessed as grade 2 or higher in the Kellgren-Lawrence classification who received PRP treatment from January 2022 to November 2023 and were followed up for at least three months. PRP was prepared with 27 mL of blood collected from the patient, and 2.7 mL of PRP was prepared using the PEAK©︎PRP System from DePuy Synthes (Raynham, MA). Intra-articular injections of PRP were performed under echo-guided procedures, and responders or non-responders were determined using the Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) criteria evaluated by the Japanese Knee Injury and Osteoarthritis Outcome Score (J-KOOS) at three months after PRP injection. The clinical efficacy of PRP treatment for KOA was assessed in this study, and a dichotomous analysis was performed comparing the responder group and the non-responder group using patient characteristics and assessed data from plain X-ray images and MRI to determine prognostic factors for PRP treatment. The study population included 36 knees with a mean age of 70.6. ± 9.2 years, comprising six knees in men and 30 knees in women. The responder group consisted of16 knees (44.4%), and the non-responder group consisted of 20 knees (55.6%).J-KOOS subscores at pre-treatment elicited that each subscale in the R group was significantly lower than that in the NR group at pretreatment. A dichotomous analysis for the two groups revealed the distribution of sex and past medical history of hyperlipidemia to be significantly different between the two groups. Multivariable logistic regression analysis showed that the coexistence of hyperlipidemia was the main prognostic factor for the efficacy of PRP therapy. In this study, comparisons were conducted between responders and non-responders to estimate prognostic factors for the efficacy of PRP therapy. Surprisingly, responders to the treatment tended to show lower J-KOOS scores and to have hyperlipidemia. A literature review revealed conflicting reports on prognostic factors for PRP therapy in KOA, highlighting the need for further research.

Effectiveness of Rehabilitation for Osteoarthritis of the Knee: A Scoping Review of Network Meta-Analyses.

Although an increasing number of network meta-analyses have been conducted on the effectiveness of conservative therapy for knee osteoarthritis, these may have been poorly planned and executed.We aimed to review the qualities of a comprehensive set of network meta-analyses on rehabilitation therapies for knee osteoarthritis and provide an overview of the effectiveness of each therapy. The eligibility criteria were as follows: (i) conservative rehabilitation was the primary treatment in the intervention group, (ii) included patients were diagnosed with knee osteoarthritis, and (iii) patient groups were aged ≤75 years, and rehabilitation interventions comprised exercise, orthotic, or physical therapies or patient education. Two independent reviewers screened the titles and abstracts of the identified records and selected the eligible reviews; their full texts were further assessed for eligibility. Then, a checklist derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for the reporting of systematic reviews incorporating network meta-analyses of healthcare Interventions was used to validate the completeness of the reporting of each network meta-analysis. Furthermore, the statistical and outcome data regarding the quality of life, knee joint function and pain, adverse events, and physical functions were extracted using a customized spreadsheet. Overall, 2701 titles and abstracts were screened, and eight network meta-analyses were ultimately selected. Nearly all reviews adequately addressed the PRISMA extension checklist, and the completeness of reporting was adequate; therefore, all expected information could be extracted. However, the methodology used to confirm the transitivity assumption was insufficient in many reviews. The following interventions were effective in reducing pain and improving physical function: (i) strengthening, flexibility, aerobic, and mind-body exercises, (ii) pulsed ultrasound, (iii) focused and radial extracorporeal shockwave therapy, and (iv) continuous ultrasound. The following interventions were effective in improving the quality of life: (i) strengthening, (ii) mixed, and (iii) mind-body exercises. Our results suggested that exercise therapies, including muscle-strengthening, aerobic, flexibility, and mind-body exercises, are likely to be effective for pain relief and functional improvement in knee osteoarthritis. This may be the first review to provide a comprehensive perspective for considering priorities for future rehabilitation interventions for knee osteoarthritis.

The efficacy of extracorporeal shock wave therapy for knee osteoarthritis : an umbrella review

Background: An umbrella review was conducted to compare the effectiveness of extracorporeal shock wave therapy (ESWT) versus non-ESWT in the treatment of knee osteoarthritis (KOA). Materials and methods: Three databases including PubMed, Embase and Web of science were searched up to September 2023. Literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Meta-analysis of outcome indicators was performed using Revman 5.4 software. Results: A total of eight meta-analysis were included in this umbrella review. All meta-analysis were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and scored between 8 and 11. Compared to the sham group, the ESWT group showed better results in WOMAC (Western Ontario and McMaster Universities Arthritis Index) [mean difference (MD)=−2.94, 95% CI: −5.52, −0.37, P=0.03, I²=60%], Visual Analog Scale (VAS) (MD=−2.0, 95% CI: −2.5, −1.5, P&lt;0.01, I²=0%), range of motion (ROM) (MD=17.55, 95% CI: 13.49, 21.61, P&lt;0.00001, I²=0%), and Lequesne index (MD=−2.85, 95% CI: −3.64, −2.07, P&lt;0.00001, I²=48%). Conclusion: Based on the results of our analysis, ESWT is now an effective therapy for improving pain and function in patients with KOA.

Lipoxin A4 ameliorates knee osteoarthritis progression in rats by antagonizing ferroptosis through activation of the ESR2/LPAR3/Nrf2 axis in synovial fibroblast-like synoviocytes

BackgroundOur previous studies have shown that lipoxin A4 (LXA4) can serve as a potential biomarker for assessing the efficacy of exercise therapy in knee osteoarthritis (KOA), and fibroblast-like synoviocytes (FLSs) may play a crucial role in KOA pain as well as in the progression of the pathology. ObjectiveBy analyzing the GSE29746 dataset and collecting synovial samples from patients with different Kellgren–Lawrence (KL) grades for validation, we focused on exploring the potential effect of LXA4 on ferroptosis in FLSs through the ESR2/LPAR3/Nrf2 axis to alleviate pain and pathological advancement in KOA. MethodsThe association between FLSs ferroptosis and chondrocyte matrix degradation was explored by cell co-culture. We overexpressed and knocked down LPAR3 in vitro to explore its potential mechanism in FLSs. A rat model of monosodium iodoacetate (MIA)-induced KOA was constructed and intervened with moderate-intensity treadmill exercise and intraperitoneal injection of PHTPP to investigate the effects of the LXA4 intracellular receptor ESR2 on exercise therapy. ResultsESR2, LPAR3, and GPX4 levels in the synovium decreased with increasing KL grade. After LXA4 intervention in the co-culture system, GPX4, LPAR3, and ESR2 were upregulated in FLSs, collagen II was upregulated in chondrocytes, and MMP3 and ADAM9 were downregulated. LPAR3 overexpression upregulated the expression of GPX4, Nrf2, and SOD1 in FLSs, while downregulating the expression of MMP13 and MMP3; LPAR3 knockdown reversed these changes. Moderate-intensity platform training improved the behavioral manifestations of pain in KOA rats, whereas PHTPP treatment partially reversed the improvement in synovial and cartilage pathologies induced by platform training. ConclusionLXA4 inhibited FLSs ferroptosis by activating the ESR2/LPAR3/Nrf2 axis, thereby alleviating the pain and pathological progression of KOA. This study brings a new target for the treatment of KOA and also leads to a deeper understanding of the potential mechanisms of exercise therapy for KOA.

Efficacy of Mulligan MWMs along with Conventional Physical Therapy in Knee Osteoarthritis

Background: Knee osteoarthritis is a prevalent degenerative joint disease that impairs mobility and causes significant pain, particularly in the aging population. Conservative management, including physical therapy, remains a cornerstone of treatment. The addition of Mulligan Mobilization with Movement (MWM) to conventional therapy has been proposed to improve outcomes, though its efficacy had not been robustly quantified. Objective: The objective of this study was to compare the efficacy of Mulligan MWM in conjunction with conventional physical therapy to conventional physical therapy alone in reducing pain and stiffness and improving functional outcomes in patients with grade 2 knee osteoarthritis. Methods: This randomized clinical trial included 28 participants with grade 2 knee osteoarthritis, randomly allocated into two groups: one receiving Mulligan MWM alongside conventional physical therapy and the other receiving only conventional physical therapy. The intervention lasted one month, with assessments conducted at baseline, two weeks, and four weeks using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as outcome measures. Statistical analysis was performed using SPSS version 25. Results: The MWM plus physical therapy group exhibited a greater reduction in VAS scores (baseline: 6.71, SD 1.729 to week 4: 2.21, SD 1.051) compared to the physical therapy alone group (baseline: 7.14, SD 1.562 to week 4: 3.86, SD 0.663), with a significant mean difference (P&lt;0.001). Similarly, WOMAC scores for pain, stiffness, and physical function significantly improved in the MWM group compared to the physical therapy group at week 4 (Pain: 2.79 vs. 6.86, Stiffness: 1.14 vs. 3.36, Function: 9.79 vs. 27.57, all P&lt;0.001). Conclusion: Mulligan MWM combined with conventional physical therapy was more effective than conventional physical therapy alone in reducing pain, stiffness, and improving functional outcomes in patients with grade 2 knee osteoarthritis. These results support the inclusion of MWM in the management of knee osteoarthritis.

Unlocking the Potential: The Importance of Mesenchymal Stem Cell Therapy for Knee Osteoarthritis

Mesenchymal stem cell (MSC) therapy for knee osteoarthritis has emerged as a revolutionary approach to address the root cause of this debilitating condition. This editorial provides a concise overview of the significance of MSC therapy in the context of knee osteoarthritis treatment. Knee osteoarthritis is a common and costly condition that affects millions worldwide, necessitating a paradigm shift in treatment strategies. Current approaches primarily focus on symptom management, leaving the underlying cartilage degeneration unaddressed. MSC therapy offers the potential to regenerate damaged cartilage, reduce pain, improve function, and potentially delay the need for surgery. This minimally invasive and safe procedure presents a promising avenue for patients seeking long-lasting relief from knee osteoarthritis. However, while the therapy shows significant potential, ongoing research, clinical trials, and efforts to ensure accessibility and affordability are essential for realizing its full impact. In conclusion, MSC therapy represents a beacon of hope for those afflicted by knee osteoarthritis, holding the promise of transforming a debilitating condition into a manageable one and thereby enhancing the quality of life for countless individuals.&#x0D; Keywords: mesenchymal stem cell therapy, knee osteoarthritis, cartilage regeneration, minimally invasive treatment, introduction

TREATMENT OF OSTEOARTHROTIS OF THE KNEE : SYSTEMATIC REVIEW

Background: Osteoarthritis (OA) of the knee, also referred to as degenerative joint disease of the knee, is usually caused by gradual articular cartilage loss as well as wear and tear. Seniors are more likely to experience it. Aims : This systematic review is to review the effect and efficacy of the therapy of knee osteoarthritis. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, ScienceDirect and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 36.803 articles, whereas the results of our search on SAGEPUB brought up 10.021 articles, our search on SCIENCE DIRECT brought up 51.811 articles. The results of the search conducted for the last year of 2014 yielded a total 22.949 articles for PubMed, 6.322 articles for SAGEPUB and 28.399 articles for SCIENCE DIRECT. In the end, we compiled a total of 8 papers, 2 of which came from PubMed, 2 of which came from SAGEPUB and 4 of which came from SCIENCE DIRECT. We included eight research that met the criteria. Conclusion: In summary, although we discovered that several treatments worked, we were unable to rate the effects since the network as a whole lacked coherence and strong confidence in the treatment comparisons.

Prognostic value of B-score for predicting joint replacement in the context of osteoarthritis phenotypes: Data from the osteoarthritis initiative

ObjectiveDeveloping new therapies for knee osteoarthritis (KOA) requires improved prediction of disease progression. This study evaluated the prognostic value of clinical clusters and machine-learning derived quantitative 3D bone shape B-score for predicting total and partial knee replacement (KR). DesignThis retrospective study used longitudinal data from the Osteoarthritis Initiative. A previous study used patients' clinical profiles to delineate phenotypic clusters. For these clusters, the distribution of B-scores was assessed (employing Tukey's method). The value of both cluster allocation and B-score for KR-prediction was then evaluated using multivariable Cox regression models and Kaplan-Meier curves for time-to-event analyses. The impact of using B-score vs. cluster was evaluated using a likelihood ratio test for the multivariable Cox model; global performances were assessed by concordance statistics (Harrell's C-index) and time dependent receiver operating characteristic (ROC) curves. ResultsB-score differed significantly for the individual clinical clusters (p ​< ​0.001). Overall, 9.4% of participants had a KR over 9 years, with a shorter time to event in clusters with high B-score at baseline. Those clusters were characterized clinically by a high rate of comorbidities and potential signs of inflammation. Both phenotype and B-score independently predicted KR, with better prediction if combined (P ​< ​0.001). B-score added predictive value in groups with less pain and radiographic severity but limited physical activity. ConclusionsB-scores correlated with phenotypes based on clinical patient profiles. B-score and phenotype independently predicted KR surgery, with higher predictive value if combined. This can be used for patient stratification in drug development and potentially risk prediction in clinical practice.

Navigating the Therapeutic Landscape: A Comprehensive Review of Platelet-Rich Plasma and Bone Marrow Aspirate Concentrate in Knee Osteoarthritis.

This comprehensive review provides an in-depth analysis of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) as potential treatments for knee osteoarthritis. It explores their mechanisms of action, clinical efficacy, safety considerations, and the importance of personalised treatment approaches. The review highlights promising findings regarding the ability of PRP and BMAC to alleviate symptoms, improve joint function, and potentially slow disease progression. It emphasises the need for further research into long-term outcomes, direct comparative studies, protocol standardisation, biomarker identification, and cost-effectiveness assessments to enhance clinical practice. While the review does not directly compare PRP and BMAC, it provides valuable insights into their respective roles in knee osteoarthritis management. The review aims to contribute to evidence-based advancements in regenerative therapies for knee osteoarthritis by addressing critical research priorities and refining treatment strategies.

Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews.

The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.

The therapeutic benefits of NSAIDs and physical therapy in knee osteoarthritis.

Osteoarthritis (OA) has been established as a progressive wear and tear disease of the synovial joints, which also involves a certain degree of inflammation. Considering there is no disease modifying medication available at the moment, the current guidelines focus on the symptomatic treatment of the affection. Our study aimed to evaluate the therapeutic advantages of the synergistic use of non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy in the treatment of knee osteoarthritis (KOA). The study comprised 46 individuals who were diagnosed with KOA and were admitted to the Department of Physical Medicine and Rehabilitation at the Emergency Clinical County Hospital of Craiova, Romania, between January 2021 and April 2022. All the participants received the same combination of pharmacological (Diclofenac 150 mg∕day, no more than 10 days∕month as needed) and non-pharmacological treatment (a 24-week plan of physical therapy). The patient group exhibited a statistically significant reduction in both the average Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (p=0.0142) and the average Visual Analog Scale (VAS) (p=0.0023). Additionally, there was a statistically significant increase in both the average Knee Outcome Survey-Activities of Daily Living (KOS-ADL) (p=0.0128) and the average Oxford Knee Score (OKS) (p=0.0023). The study found a significant positive correlation between higher VAS ratings and cholesterol levels (p=0.0092), but no significant correlation between VAS scores and triglyceride levels (p=0.0986). Patients were evaluated for a further 24 weeks beyond the conclusion of the research to see if surgical intervention was necessary during this time. Our investigation tracked the WOMAC, VAS, KOS-ADL, and OKS measurements in a cohort of patients with KOA. The results demonstrate that the utilization of NSAIDs in conjunction with physical therapy effectively alleviates pain and enhances joint functionality.

Mesenchymal stem cell-derived exosomes as a promising cell-free therapy for knee osteoarthritis.

Osteoarthritis (OA), as a degenerative disease, leads to high socioeconomic burdens and disability rates. The knee joint is typically the most affected and is characterized by progressive destruction of articular cartilage, subchondral bone remodeling, osteophyte formation and synovial inflammation. The current management of OA mainly focuses on symptomatic relief and does not help to slow down the advancement of disease. Recently, mesenchymal stem cells (MSCs) and their exosomes have garnered significant attention in regenerative therapy and tissue engineering areas. Preclinical studies have demonstrated that MSC-derived exosomes (MSC-Exos), as bioactive factor carriers, have promising results in cell-free therapy of OA. This study reviewed the application of various MSC-Exos for the OA treatment, along with exploring the potential underlying mechanisms. Moreover, current strategies and future perspectives for the utilization of engineered MSC-Exos, alongside their associated challenges, were also discussed.

Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities.

Knee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options. PubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. Our meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I 2=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I2=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I 2=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I 2=68%) compared to CS injections, with the most significant improvement observed at 6 months. PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.