Function In Osteoarthritis Patients Research Articles

Botulinum toxin A attenuates osteoarthritis development via inhibiting chondrocyte ferroptosis through SLC7Al1/GPX4 axis

Osteoarthritis (OA) is a prevalent joint degenerative disease, resulting in a significant societal burden. However, there is currently a lack of effective treatment option available. Previous studies have suggested that Botulinum toxin A (BONT/A), a macromolecular protein extracted from Clostridium Botulinum, may improve the pain and joint function in OA patients, but the mechanism remains elusive. This study was to investigate the impact and potential mechanism of BONT/A on OA in vivo and in vitro experiment. LPS increased the levels of ROS, Fe2+and Fe3+, as well as decreased GSH levels, the ratio of GSH / GSSH and mitochondrial membrane potential. It also enhanced the degeneration of extracellular matrix (ECM) and altered the ferroptosis-related protein expression in chondrocytes. BONT/A rescued LPS-induced decrease in collagen type II (Collagen II) expression and increase in matrix metalloproteinase 13 (MMP13), mitigated LPS-induced cytotoxicity in chondrocytes, abolished the accumulation of ROS and iron, upregulated GSH and the ratio of GSH/ GSSH, improved mitochondrial function, and promoted SLC7A11/GPX4 anti-ferroptosis system activation. Additionally, intra-articular injection of BONT/A inhibited the degradation of cartilage in OA model rats. This chondroprotective effect of BONT/A was reversed by erastin (a classical ferroptosis agonist) and enhanced by liproxstatin-1 (a classic ferroptosis inhibitor). Our research confirms that BONT/A alleviates the OA development by inhibiting the ferroptosis of chondrocytes, which revealed to be a potential therapeutic mechanism for BONT/A treating the OA.

Effectiveness of Foam Rolling with Hip Strengthening versus Conventional Treatment in Iliotibial Band Tightness Among Osteoarthritis Patients

Background: The iliotibial band (ITB) tightness contributes to pain and functional limitations in osteoarthritis (OA) patients. The effectiveness of foam rolling (FR) combined with ITB stretching exercises versus conventional treatment methods targeting ITB tightness has not been thoroughly investigated. This study aimed to evaluate the impact of these modalities on passive range of motion (PROM) during hip adduction in OA patients. Methods: Three groups of OA patients (Foam Rolling alone-Group A, Conventional Exercises + Foam Rolling-Group B, and Hip strengthening + Foam Rolling-Group C) were assessed over 14 treatment sessions using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and Ober's test for ITB tightness. Group A received foam rolling with hip strengthening, Group B underwent conventional treatment, and Group C was treated with a combination of methods. Results: All groups showed a marked decrease in WOMAC scores, indicating an improvement in pain and knee function. Group A exhibited a significant reduction in ITB tightness, with the mean Ober's test score initially increasing but then decreasing markedly by the 14th session. Group B and Group C also showed improvements, but Group A's protocol was the most effective in reducing ITB tightness. Conclusion: The study demonstrated that foam rolling with hip strengthening exercises is significantly effective in reducing ITB tightness and improving function in OA patients. This combination therapy may be considered a superior approach to conventional treatment methods for managing ITB-related symptoms in this population.

A Comparative Study of Intra-Articular Knee Injection of Leukocyte-Poor Platelet-Rich Plasma Compared to Corticosteroids and Local Anesthetics in Patients with Knee Osteoarthritis

Background: Knee osteoarthritis (OA) is the most common reason for orthopedic secondary care referral. And it is one of the main causes of disability in adults worldwide. It is estimated to affect between 10 to 25% of patients over the age of 60. Intra-articular corticosteroid injection (IA CS) and physical therapy were the two choices in an attempt to provide symptomatic management or deferred surgery. There is a growing trend is intra-articular platelet-rich plasma (IA PRP) injection to reduce pain and improve function in OA patients. PRP is divided into two types: leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP). It was shown that LR-PRP increases pro-inflammatory factors and also decreases anti-catabolic mediators, and LP-PRP has the opposite aspect.
 Methods: In our research 40 patients were divided into two equal groups, IA corticosteroid and leukocyte-poor platelet-rich plasma (LP-PRP) 40 cc of blood from the basilic vein of the upper limb is used with two step centrifugation. The final samples were 4 millilitres product injected intra-articular. group two (corticosteroid (CS)) received an intra-articular injection of triamcinolone acetate (Kenalog) 40 mg/ml along with 4 ml of lidocaine 0.02% (Abureyhan Co.) for a total of 5 ml. The needle used is a 22-gauge pencil-point Quincke needle (Dr. Japan Co, Ltd), which is performed with the Sonosite Edge II ultrasound guide and in an anterior-lateral manner in the knee joint. Pain was assessed on a visual analogue scale (VAS range 0-10 points) before, one week, one month, two month and 3 months after the operation. The WOMAC questionnaire was also filled before injection and three months following injection and other variables were examined.
 Results: There were no significant differences between the groups across all the baseline parameters including age, sex, body mass index and comorbidities including high blood pressure, diabetes and smoking. Both injection groups were effective in reducing patients' pain from one week to three months after injection. The level of pain in the first week after injection was significantly lower in the corticosteroid group than in the PRP group. In the first month and the third month after the injection, the pain reduction according to mean scores of VAS was the same in both groups.
 Conclusion: In short, one injection of PRP can reduce the pain of patients with osteoarthritis of the knee as much as corticosteroids during a three-month treatment process. Considering the possible side effects of corticosteroids, this alternative treatment can be considered with further investigation.

Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study.

This research investigates the relationship between niacin intake and knee osteoarthritis (OA) severity, focusing on pain and functional ability due to niacin's role as a NAD(P)+ precursor, promoting cellular energy, and offering anti-inflammatory, analgesic, and antioxidant effects. The population-based Osteoarthritis Initiative (OAI) cohort with radiographically confirmed knee OA was analyzed through a Food Frequency Questionnaire determining niacin intake and scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using generalized additive mixed models. A significant correlation was pinpointed in 2375 OA patients (1001 men and 1374 women; 55.96% aged between 45 and 65 and 44.04% aged ≥65) between niacin intake and reduced knee pain and functional degrees after a 48-month follow-up, evident in improved KOOS and WOMAC scores (P < 0.05). The fully adjusted models estimated a decrease of 0.26 points for every additional 1 unit of Ln-niacin intake of daily niacin intake on the WOMAC pain subscale, 0.83 points on the WOMAC function subscale, and an increase of 1.71 and 1.58 on the KOOS pain and quality of life score. Strikingly, subgroups including middle-aged individuals, women, white race, obese individuals, and those with specific dietary habits showed a more substantial improvement with increased niacin. The association between increased niacin intake and reduced pain and function scores, as well improved quality of life in knee OA patients, is significant. Certain cohorts, according to a stratified analysis, could see more considerable benefits with increased niacin consumption. • Increased niacin intake is linked to reduced knee pain and better function in OA patients. • Specific subgroups, such as middle-aged individuals, women, and those with certain dietary habits, benefit more from increased niacin consumption. • Niacin shows promise for enhancing the quality of life in knee OA patients by reducing pain and improving function.

Treatment with CR500® improves algofunctional scores in patients with knee osteoarthritis: a post-market confirmatory interventional, single arm clinical investigation

BackgroundKnee osteoarthritis (OA) is a progressive and degenerative condition. Several pharmacological and non-pharmacological treatments are able to improve the OA symptoms and the structural characteristics of the affected joints. Among these, infiltrative therapy with hyaluronic acid (HA) is the most used and consolidated procedure for the pain management. The addition of skin conditioning peptides to HA promotes the cartilage remodeling processes and a better permeation of the HA-based gel containing a peptide mixture, CR500®. Furthermore, the topic route of administration is convenient over the routinely used intra-articular injective procedures. In this study, the effectiveness of CR500® was evaluated in terms of improvement of the algo-functional symptoms related to unilateral knee OA.Methods38 mild and moderate OA patients were enrolled at a screening visit (V-1), treated at baseline visit (V1), and then continued the topical application of CR500® twice a week for 4 weeks, and followed-up for 3 visits (V2-V4) from week 2 to 4. Lequesne Knee Index (LKI) and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Synovial fluid was collected and used for the quantification of neoepitope of type II collagen (C2C), C-terminal telopeptide of type II collagen (CTX-II), type II collagen propeptide (CPII), tumor necrosis factor alpha (TNFα) and HA. The expression of CD11c and CD206 was evaluated on cell pellets.ResultsThree patients were excluded, thus 35 patients were included in the analysis. The treatment with CR500® was safe and well tolerated, with 7.9% patients had mild adverse events, not related to the device. The LKI total score showed a significant decrease from V1 to V4. KOOS score also showed a significant improvement of patient condition at V2, V3 and V4 in comparison with V1 for all subscales, except for KOOS sport subscale which improved only from V3. At V1 a negative correlation among KOOS pain subscale values and C2C, CPII and TNFα levels was observed, as well as a positive correlation between KOOS pain subscale and CD11c/CD206 ratio.ConclusionCR500® is safe and appear to be effective in improving pain and function in OA patients during the 4 weeks of treatment.Trial registrationClinicalTrials.gov ID: NCT05661162. This trial was registered on 22/12/2022.

Effect of knee arthroscopic debridement combined with peripatellar denervation on restoration of knee function in patients with knee osteoarthritis

BackgroundThis research examines knee osteoarthritis (OA), a prevalent orthopedic disease marked by cartilage degeneration and chronic synovitis, leading to pain, restricted mobility, and eventual loss of knee function. Notably, patellofemoral osteoarthritis constitutes a significant proportion of knee OA cases. Our study aims to assess the impact of knee arthroscopic debridement coupled with peripatellar denervation on restoring knee function in OA patients and analyze the risk factors affecting treatment outcomes. By doing so, we hope to contribute to the informed selection of clinical treatment plans, addressing a disease that, if untreated, significantly impairs patients’ quality of life.MethodsA total of 211 patients with knee osteoarthritis treated in our hospital from June 2020 to June 2022 were analyzed retrospectively. Among them, 116 patients received arthroscopic knee debridement treatment alone as the control group, and 95 in the observation group were combined with denervation treatment based on the control group. The clinical efficacy of the two groups of patients after treatment was evaluated, and patients’ pain was counted using the pain visual analogue score (VAS) method. The knee range of motion (ROM) was used to count the mobility of the patients and to compare the operative time, intraoperative perfusion volume, and length of stay between the two groups. According to the effectiveness after treatment, patients were divided into the improvement group (effective + markedly effective) and the non-improvement group, and the risk factors affecting the clinical efficacy of patients after treatment were analyzed by logistic regression.ResultsThe total treatment efficiency of patients in the control group was lower than that of those in the observation group (P < 0.05). There was no difference in intraoperative perfusion volume and length of stay between patients in both groups (P > 0.05). However, the operative time was shorter in the control group compared with that in the observation group (P < 0.001). The post-treatment VAS scores of patients in the observation group were lower than those in the control group, while the ROM scores were higher than those of the control group (P < 0.001). Age, BMI, and preoperative VAS score were found to be independent risk factors for patient outcome by logistic regression analysis (P < 0.05).Conclusionknee arthroscopic debridement combined with peripatellar denervation has a significant improvement in the restoration of knee function in patients with knee osteoarthritis and reduces their level of pain.

Recent advances in mesenchymal stem/stromal cells (MSCs)-based approaches for osteoarthritis (OA) therapy.

Recently, mesenchymal stem/stromal cells (MSCs) transplantation has been introduced as a promising option to support cartilage structure and improve its function in preclinical models and patients suffering from osteoarthritis (OA). MSCs strongly provoke their preferred influence in vivo by inhibiting the inflammatory responses and applying immunomodulation by releasing anti-inflammatory mediators such as transforming growth factor-β and interleukin-10. Such mediators downregulate fibroblast-like synoviocytes growth and migration, leading to chondroprotection. Furthermore, improving the chondrocyte proliferation and extracellular matrix hemostasis in addition to the suppression of the matrix metalloproteinases activities can support cartilage tissue organization. In this light, various published results have demonstrated that MSCs therapy can considerably decrease pain and restore knee function in OA patients. In the current review, we have concentrated on recent advances in MSCs-based therapeutics to elicit both chondrogenic and chondroprotective impacts in OA patients, focusing on the last decade in vivo results.

Mapping of disease-specific Oxford Knee Score onto EQ-5D-5L utility index in knee osteoarthritis

BackgroundEQ5D is a generic measure of health. It provides a single index value for health status that can be used in the clinical and economic evaluation of healthcare. Oxford Knee Score (OKS) is a joint-specific outcome measure tool designed to assess symptoms and function in osteoarthritis patients after joint replacement surgery. Though widely used, it has the disadvantage of lacking health index value. To fill the gap between functional and generic questionnaires with economic value, we linked generic EQ-5D-5L to the specific OKS to give a single index value for health status in KOA patients.Questions/purposesDeveloping and evaluating an algorithm to estimate EuroQoL generic health utility scores (EQ-5D-5L) from the disease-specific OKS using data from patients with knee osteoarthritis (KO).Patients and methodsThis is a cross-sectional study of 571 patients with KO. We used four distinct mapping algorithms: Cumulative Probability for Ordinal Data, Penalized Ordinal Regression, CART (Classification and Regression Trees), and Ordinal random forest. We compared the resultant models’ degrees of accuracy.ResultsMobility was best predicted by penalized regression with pre-processed predictors, usual activities by random forest, pain/discomfort by cumulative probability with pre-processed predictors, self-care by random forest with RFE (recursive feature elimination) predictors, and anxiety/depression by CART with RFE predictors. Model accuracy was lowest with anxiety/depression and highest with mobility and usual activities. Using available country value sets, the average MAE was 0.098 ± 0.022, ranging from 0.063 to 0.142; and the average MSE was 0.020 ± 0.008 ranging from 0.008 to 0.042.ConclusionsThe current study derived accurate mapping techniques from OKS to the domains of EQ-5D-5L, allowing for the computation of QALYs in economic evaluations. A machine learning-based strategy offers a viable mapping alternative that merits further exploration.

Relative safety and efficacy of topical and oral NSAIDs in the treatment of osteoarthritis: A systematic review and meta-analysis.

Osteoarthritis (OA) often affects the hands, knees, and hip joints, causing considerable pain and disability, and often affecting the patient's quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are common pain relievers often applied as first line therapies for OA. However, prolonged NSAIDs application can have unwanted side effects. Given this, this study was designed to systematically evaluate the efficacy and safety of topical and oral NSAIDs for the treatment of OA. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant papers from their inception dates to May 2021. Our study only included randomized controlled trials comparing topical and oral NSAIDs and all data were analyzed using Review Manager version 5.3 (RevMan version 5.3). We identified 8 RCTs (2096 patients with OA), for evaluation and revealed that, in general, topical and oral NSAIDs presented with similar efficacies for the treatment of OA. The Western Ontario and McMaster Osteoarthritis Index for assessing pain relief in OA patients was (standardized mean difference [SMD] 0.07; 95%CI -0.02, 0.17) and visual analog scale was (SMD -0.01; 95%CI -0.02, 0.18), and improved stiffness in OA patients (SMD 0.09; 95%Cl 0.03, 0.20). Topical NSAIDs are as effective as oral NSAIDs for the treatment of OA and both topical and oral NSAIDs are equally effective in reducing pain and improving physical function in OA patients. In terms of safety, a larger number of samples are still needed to determine if there are any differences in the safety profile of topical or oral NSAIDs. INPLASY 2021110009.

Relationship between Histological Changes of the Anterior Cruciate Ligament and Knee Function in Osteoarthritis Patients

Relationship between Histological Changes of the Anterior Cruciate Ligament and Knee Function in Osteoarthritis Patients

The effect of intra-articular ozone injection on pain and physical function in knee osteoarthritis: A prospective study

Introduction: This study aims to evaluate the effect of intra-articular ozone treatment on pain and physical functionality by measuring Numerical Pain Rating Scale (NRS), WOMAC Osteoarthritis Index (WOMAC-OI), and Active Joint Range of Motion (AROM) in patients diagnosed with osteoarthritis. Material and methods: A total of 30 patients diagnosed with stage 2-3 osteoarthritis according to the Kellgren-Lawrence Classification System (K-L) were included in the study. Ozone gas was administered (10 ml of 10 mcg/ml per session) twice weekly for a total of four sessions. AROM examination was performed at pre-treatment baseline (BL), post-treatment (PT), and two weeks after treatment (PT2). During these periods, NRS was assessed and WOMAC-OI questionnaire was administered. Results: Significant improvement in NRS and WOMAC-OI total index scores were observed at PT and PT2 periods compared to BL (6.9±1.2; 2.1±1.3; 3.3±1.1; WOMAC-OI total index: 48.1±10.1; 25.5±10.4; 29.1±11.1 respectively; p˂0.001 for all). However, in both of these evaluation methods, the recovery at PT2 had decreased compared to the PT period (NRS p˂0.001; WOMAC-OI p˂0.05). Significant improvement was observed in the AROM values measured during the PT and PT2 periods, compared to baseline (105.6 ± 10.4°; 118.8 ± 8.1°; 117.5 ± 9.2°, respectively) (p˂0.001). There was no difference between the PT and PT2 periods in terms of AROM measurements (p˃0.05). Conclusion: Our study demonstrates that intra-articular ozone injection treatment provides improvement in pain and physical functionality in osteoarthritis patients. In our two-month follow-up assessment, although evaluation methods indicated that there was regression in recovery, AROM measurements showed that there was no regression in function. Therefore, we believe that future studies may include AROM as an objective measurement among evaluation methods.

Development, characterization and research of efficacy on in vitro cell culture of glucosamine carrying hyaluronic acid nanoparticles

Intra-articular hyaluronic acid (HA) and oral glucosamine (GA) are frequently used to decrease pain and increase function in osteoarthritis patients. Injectable chondroitin sulfate and HA improve effectiveness however a formulation that combines GA and HA is currently not available. Aims of this study were to synthesize and characterize N-acetyl-d-GA immobilized HA based nanoparticles [GA-PEG@nano(HA)] to increase extracellular matrix production and to decrease OA markers of healthy and OA chondrocytes. Mean size of synthesized GA-PEG@nano(HA) was 175 nm and 20% of GA released from these composites during 21 days. Released GA reduced the proliferation of chondrosarcoma cells. Chondrogenic marker expression of bone marrow mesenchymal stem cells decreased slightly but not significantly. osteoarthritis and extracellular matrix markers of healthy and osteoarthritic chondrocytes at seven days in culture remained unchanged. In conclusion, GA-PEG@nano(HA) composites had limited effects on mesenchymal stem cells, healthy and osteoarthritic chondrocytes.

Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study

Clinical data demonstrating efficacy for nutraceutical compounds marketed for the symptom relief of osteoarthritis (OA) have been largely contentious. Furthermore, no association has been linked between clinical trial inconsistencies and gastrointestinal (GI) dysfunction. The aim of this study was to primarily investigate the efficacy of a high-dose New Zealand green-lipped mussel (GLM) extract in patients diagnosed with OA of the knee and concurrently assess GLM impact on GI function. An open label, single group allocation study was conducted, that administered 3,000 mg/day of GLM extract over 8 weeks to 21 subjects diagnosed with knee OA. Outcome measures were scored using the WOMAC, the Lequesne algofunctional index, and the Gastrointestinal Symptom Rating Scale (GSRS) tools. An intention-to-treat analysis was employed and subject data collected at T₀, T₄ and T₈ weeks. Paired t tests showed significant improvement for the Lequesne, WOMAC (p < 0.001) and GSRS (p = 0.005) scores. A repeated measures ANOVA analysis showed significant improvement in scores for the Lequesne (F = 20.317, p < 0.001), WOMAC (F = 28.383, p < 0.001) and the GSRS (F = 9.221, p = 0.002). Green-lipped mussel significantly improved knee joint pain, stiffness and mobility. We report for the first time that the administration of GLM extract also significantly improved GI symptoms by 49% in OA patients. Given that GI dysfunction is linked to analgesic medication use, we further conclude that the therapeutic efficacy of the GLM extract used was possibly correlated to its effects on GI function by improving GSRS scores from baseline. Results from this trial highlight the requisite for further clinical investigations of gastrointestinal tract function in OA patients.

Use of Viscosupplementation for Knee Osteoarthritis

Because of the rising numbers of patients affected by osteoarthritis (OA), management decisions on how to minimize pain and improve function in OA patients are important. Intra-articular hyaluronic acid (IAHA) knee injections have become a common treatment in the management of knee OA. In an editorial appearing in the 2007 National Knowledge Week on Osteoarthritis: National Health Service Evidence, four questions were asked about the clinical use of IAHA treatment for OA: 1) Who is the ideal candidate for HA viscosupplementation? 2) Do the mechanical and biological effects differ in importance in different stages of the disease? 3) What is the ideal dose in early- and late-stage OA? 4) Can the biological effect be delivered by means other than injection? These key issues are addressed. On the basis of results from several systemic reviews and meta-analyses, we conclude that IAHA knee injections in patients with knee OA result in modest improvements when measured by validated outcomes.

The multicomponent phytopharmaceutical SKI306X inhibits in vitro cartilage degradation and the production of inflammatory mediators

Clinical studies have demonstrated that SKI306X, a purified preparation of three medicinal plants, relieves joint pain and improves functionality in osteoarthritis patients. To study the biological action of SKI306X, bovine cartilage explants and human peripheral blood mononuclear cells (PBMC) were stimulated with IL-1 beta and lipopolysaccharide (LPS) respectively, in the presence or absence of SKI306X and its individual composites. All tested compounds inhibited dose-dependently IL-1 beta-induced proteoglycan release and nitric oxide production by cartilage, indicating cartilage protective activity. SKI306X and two of its compounds inhibited PGE(2), TNF-alpha and IL-1 beta production by LPS-stimulated PBMC, indicating anti-inflammatory activity. These results demonstrate that the biological effect of SKI306X is at least bipartite: (1) cartilage protective and (2) anti-inflammatory. The observed anti-inflammatory effects may provide an explanation for the outcome of the clinical studies. Long-term clinical trails are necessary to elucidate whether the in vitro cartilage protective activity results in disease-modifying effects.

Management of osteoarthritis in the primary-care setting: An evidence-based approach to treatment

The most prevalent musculoskeletal condition that results in joint pain is osteoarthritis (OA), with nearly 70% of the population >65 years of age demonstrating radiographic evidence of this disease. The knee is the joint commonly affected. Therapy for OA of the knee is directed at decreasing joint pain and increasing function and includes both pharmacologic and nonpharmacologic interventions. Pharmacologic therapy begins with analgesic medications and proceeds to topical analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) as needed. Intra-articular injections of corticosteroids can relieve pain and inflammation but the effect is of very short duration and such therapy should only be employed infrequently. Nonpharmacologic therapy should include patient education, weight loss if clinically indicated, physical therapy directed at maintaining joint mobility and strengthening muscle groups or an organized low-impact exercise program, and assistive devices as needed. Total joint replacement appears to be a successful therapy when joint pain severely limits a patient's ability to function. Experimental therapies to modify pain and function in OA patients include intra-articular injections of hyaluronan or arthroscopic joint lavage and debridement. In summary, both pharmacologic and nonpharmacologic measures can contribute to the treatment of pain from OA of the knee.