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Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Orthopedics".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 12830

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Dr. Wiesław Tomaszewski

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1. ARS MEDICA Foundation for Medical Education and Promotion of Health, Art and Culture, 04-036 Warsaw, Poland
2. College of Physiotherapy in Wrocław, Wrocław, Poland
Interests: orthopaedic surgery; minimal invasive techniques; osteoarthritis; sports medicine (physical activity in the prevention and treatment of lifestyle diseases)

Dr. Wojciech Glinkowski

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1. Polish Telemedicine and eHealth Society, Targowa 39A-5, PL-03728 Warsaw, Poland
2. Center of Excellence "TeleOrto" for Telediagnostics and Treatment of Disorders and Injuries of the Locomotor System, Department of Medical Informatics and Telemedicine, Medical University of Warsaw, PL-00581 Warsaw, Poland
Interests: orthopaedic surgery; spine surgery; telemedicine; eHealth; telerehabilitation; telediagnostics; patient-oriented outcomes; PROMIS® (Patient-Reported Outcomes Measurement Information System); quantitative methods; joint preservation; osteoarthritis; osteoporosis; minimally invasive techniques
Special Issues, Collections and Topics in MDPI journals

Dr. Grzegorz Szczȩsny

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Department of Orthopedic Surgery and Traumatology, Medical University, 02-005 Warsaw, Poland
Interests: orthopaedic surgery; osteoarthritis; osteoporosis; joint surgery
Special Issues, Collections and Topics in MDPI journals

Dr. Przemysław Paradowski

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1. Department of Surgical and Perioperative Sciences, Division of Orthopedics, Sunderby Research Unit, Umea University, Sunderby Central Hospital of Norrbotten, SE-971 80 Lulea, Sweden
2. Clinical Epidemiology Unit, Orthopedics, Department of Clinical Sciences Lund, Lund University, SE-221 85 Lund, Sweden
Interests: osteoarthritis (osteoarthritis in clinical and radiographic assessment, diagnosis criteria, and assessment of progression of changes); orthopedic surgery

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is a common chronic joint disease causing pain, disability, and loss of function. It is currently the fourth most common cause of disability in women and the eighth in men, and shows a global over 100% trend of an increase in the number of years lived with disability over the last three decades. It is among the ten diseases generating the highest social costs. As many as 5% of the world's population requires constant treatment due to pain and related disorders of the musculoskeletal system caused by this disease. It causes debilitating multi-joint changes, causes pain that impairs motor skills, limits the ability to move freely and perform everyday as well as professional activities, and significantly worsens quality of life. OA's etiology includes mechanical and biological events that lead to an imbalance between the interconnected processes of the breakdown and formation of articular cartilage as well as the subchondral bone layer. This process can be initiated by many factors: genetic, developmental, metabolic, and traumatic. OA is manifested by morphological, biochemical, molecular, and biomechanical changes both within cells and the matrix, leading to softening, fibrosis, the formation of cartilage erosions and defects, the “densification” of subchondral bone tissue, and the formation of osteophytes as well as subchondral cysts. Does osteoarthritis have to be the incurable epidemic of our times? Does the complete replacement of the joint with an artificial one remain the primary form of treatment? What can and should be used in the treatment procedure before arthroplasty, or are there practical ways to prevent the need for surgery? Such questions remain open. Many scientific studies bring us closer to understanding osteoarthritis’s etiology, pathogenesis, and natural course. However, we still need to know more to assess joint failure risk, and it is not enough to prevent and treat the disease in its early stages. Further scientific research will allow us to understand the nature of the disease better and find more effective ways to treat it.

The Special Issue of the Journal of Clinical Medicine is devoted to OA etiology and pathogenesis as well as modern methods of diagnosis, conservative treatment, and joint preservation. We accept original research, clinical papers, and review papers based on the latest literature reports.

Dr. Wiesław Tomaszewski
Dr. Wojciech Glinkowski
Dr. Grzegorz Szczȩsny
Dr. Przemysław Paradowski
Guest Editors

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Keywords

osteoarthritis
etiopathogenesis of osteoarthritis
articular cartilage
OA treatment
joint preservation

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Published Papers (9 papers)

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Research

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19 pages, 569 KiB

Open AccessArticle

Intra-Articular Administration of PBHSCs CD34+ as an Effective Modality of Treatment and Improving the Quality of Life in Patients with Coxarthrosis

by Marek Krochmalski, Marek Kiljański, Jakub Krochmalski, Piotr Grzelak, Karolina Kamecka, Mariusz Mianowany and Jarosław Fabiś

J. Clin. Med. 2025, 14(8), 2656; https://doi.org/10.3390/jcm14082656 - 12 Apr 2025

Viewed by 443

Abstract

Background/Objectives: In 2020, 595 million world citizens had osteoarthritis, and the largest growth in OA morbidity refers to the hip joint. Effective OA therapies have been sought for years. Assessing the treatment effectiveness and QoL improvement in hip OA after intra-articular administration of fresh peripheral blood hematopoietic CD34+ stem cells. Methods: The study comprised 49 adults (median age: 63). The SCs were injected into hip joints and straight to the bone. Hip manipulation was conducted. Patients were subjected to a standardized rehabilitation protocol. Hip degeneration was graded by Kellgren–Lawrence. Multi-factor statistical analyses, with replications, were performed. The study was an R&D project, co-financed by the E.U. Results: Patient-reported outcomes (HOOS, SF-36) ameliorated remarkably over 24 months (p < 0.0001). Ranges of movement improved significantly (p < 0.0001). The most noticeable improvement manifested 6 months after the SC administration. Its furtherance was maintained. Conclusions: Intra-articular administration of CD34+ cells significantly reduces pain and improves hip joint function, regardless of the severity of OA, according to K-L, over a 24-month follow-up period. The combination of CD34+ cell therapy with joint mobilization and rehabilitation allows for the postponement of hip arthroplasty by significantly improving patients’ QoL over the 24-month follow-up period. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

26 pages, 4386 KiB

Open AccessArticle

The Expression Level of SOX Family Transcription Factors’ mRNA as a Diagnostic Marker for Osteoarthritis

by Kamila Baran, Ewa Brzeziańska-Lasota, Jakub Kryczka, Joanna Boncela, Aleksandra Czechowska, Karolina Kopacz, Gianluca Padula, Krzysztof Nowak and Marcin Domżalski

J. Clin. Med. 2025, 14(4), 1176; https://doi.org/10.3390/jcm14041176 - 11 Feb 2025

Cited by 1 | Viewed by 901

Abstract

Background/Objectives: Osteoarthritis (OA) is the most common degenerative and chronic joint disease and is a leading cause of pain and disability in adults worldwide. The SRY-related HMG box (SOX) family transcription factors (TFs) play a crucial role during the pathogenesis of OA; however, their exact mechanisms remain unexplored. The aim of our study was to conduct a bioinformatics analysis of the common interactions of SOX-5, SOX-9, and SOX-11 with other proteins, as well as their role in OA pathogenesis. Methods:SOX5, SOX9, and SOX11 mRNA expression levels in articular cartilage with subchondral bone and synovium from knee OA patients were assessed using the qPCR method. The study group consisted of thirty-one patients (n = 31). Total RNA was isolated from the articular cartilage with subchondral bone and synovium from the affected and unaffected area of the knee joint. Results: Our results revealed a regulatory network between SOX-5, SOX-9, and SOX-11, and various proteins involved in the pathogenesis of knee OA and their collective interactions, which are involved in the regulation of cartilage extracellular matrix (ECM) organization, response to stimulus, regulation of gene expression, inflammatory response, cartilage condensation, and ossification in chondrocytes. Higher expression levels of SOX5, SOX9, and SOX11 mRNA were noted in OA-affected articular cartilage with subchondral bone compared to control tissue (p = 0.00015, p = 0.0024 and p > 0.05, respectively, Mann–Whitney U-test). All studied genes demonstrated elevated mRNA expression levels in the articular cartilage with subchondral bone from stage 4 patients than those with stage 3 (p > 0.05; Mann–Whitney U-test). Lower SOX5, SOX9, and SOX11 mRNA expression levels were found in OA-affected synovium compared to the control tissue (p = 0.0003, p > 0.05 and p = 0.0007, respectively, Mann–Whitney U-test). Decreased SOX9 mRNA expression levels in synovium were noted in patients with stage 4 disease than those with stage 3; however, SOX5 and SOX11 mRNA expression levels were higher in patients with stage 4 (p > 0.05; Mann–Whitney U-test). Conclusions: The results of our research show that the studied SOX TFs play a role in the development of OA, contributing to the formation of pathological changes not only in the articular cartilage, but also in the synovial membrane. The changes in the SOX5, SOX9, and SOX11 mRNA expression levels in the articular cartilage with subchondral bone and synovium may serve as potential molecular diagnostic biomarkers for detecting OA and could indicate the progression of this disease; however, our observations require further investigation. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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10 pages, 1467 KiB

Open AccessArticle

Short-Term Effects of Cooled Radiofrequency Ablation on Walking Ability in Japanese Patients with Knee Osteoarthritis

by Kentaro Hiromura, Hironori Kitajima, Chie Hatakenaka, Yoshiaki Shimizu, Terumasa Miyagaki, Masayuki Mori, Kazuhei Nakashima, Atsushi Fuku, Hiroaki Hirata, Yoshiyuki Tachi and Ayumi Kaneuji

J. Clin. Med. 2024, 13(23), 7049; https://doi.org/10.3390/jcm13237049 - 22 Nov 2024

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Abstract

Background/Objectives: Knee osteoarthritis (KOA) is a degenerative joint disease typically managed with conservative treatments, such as anti-inflammatory medications and intra-articular hyaluronic acid injections; however, advanced cases may eventually require surgical intervention. Recently, cooled radiofrequency ablation (CRFA) has emerged as a novel treatment option for alleviating KOA-related pain by temporarily disabling pain-transmitting nerves. This study evaluated the short-term effects of CRFA on pain relief and walking ability in KOA patients, with a specific focus on functional improvements in walking capacity. Methods: This study included 58 patients (71 knees) with KOA who underwent CRFA after experiencing inadequate pain control with conservative treatments. The cohort consisted of 28 men and 30 women, with a mean age of 75.2 years (55–90). Under ultrasound guidance, CRFA was performed on the superior lateral geniculate nerve, superior medial geniculate nerve, and inferior medial geniculate nerve, with each targeted nerve ablated. Pre- and post-procedural evaluations (one month after CRFA) included assessments of visual analog scale (VAS) scores for pain at rest and during walking, range of motion (ROM), knee extensor strength, walking speed, and gait stability. Results: Significant improvements in the mean VAS (rest/walking) and mean walking speed (comfortable/maximum) were observed following CRFA. However, no significant changes were noted in ROM, knee extensor strength, or walking stability. Conclusions: These findings suggest that rehabilitation may be essential to further enhance walking stability. Overall, CRFA appears to be a promising short-term treatment option for reducing VAS pain scores and enhancing walking speed in patients with KOA. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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11 pages, 2870 KiB

Open AccessArticle

Safety and Effectiveness of a Novel Liposomal Intra-Articular Lubricant in Symptomatic Knee Osteoarthritis: A First-in-Human Study

by Shai Shemesh, Oleg Dolkart, Ronit Goldberg, Sabrina Jahn, Amal Khoury, Yaniv Warschawski, Haggai Schermann, Moshe Salai, Gaby Agar and Michael Drexler

J. Clin. Med. 2024, 13(22), 6956; https://doi.org/10.3390/jcm13226956 - 18 Nov 2024

Cited by 1 | Viewed by 1156

Abstract

Background/Objectives: Osteoarthritis (OA) is a common disease that affects almost half the population at some point in their lives, causing pain and decreased functional capacity. New conservative treatment modalities are being proposed to provide symptomatic relief and delay surgical intervention. This study aimed at evaluating the safety of the novel liposomal boundary lubricant, injected intra-articularly in patients with moderate knee OA. Additionally, the effect on the functionality and life quality was assessed. Methods: Eighteen of the twenty screened subjects met inclusion criteria and were enrolled in the study. After receiving a single IA injection of AqueousJoint, patients were prospectively evaluated at baseline and at 2, 4, 8, 12, and 26 weeks. Numeric Pain Rating Scale (NRS), Knee injury and Osteoarthritis Outcome Score (KOOS), Short Form Health Survey (SF12) and range of motion were also recorded. Results: The final analysis was conducted on 18 subjects. No adverse events related to the investigational product were observed in the study. No serious adverse events were observed at all. A significant decrease in pain was demonstrated at all time points vs. baseline (Friedman X² = 35.08, p < 0.001). Significant improvement was demonstrated in KOOS pain, symptoms, sports, and ADL subscales (p < 0.001). Conclusions: Despite a relatively small sample, it was demonstrated that single IA AqueousJoint injection is a safe procedure, resulting in significant pain reduction, higher ADL score, and higher KOOS sport scores. The effects lasted up to 6 months. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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9 pages, 1281 KiB

Open AccessArticle

In Silico Modeling of Stress Distribution in the Diseased Ankle Joint

by Jacek Lorkowski, Miroslaw W. Mrzyglod and Mieczyslaw Pokorski

J. Clin. Med. 2024, 13(18), 5453; https://doi.org/10.3390/jcm13185453 - 13 Sep 2024

Viewed by 1167

Abstract

Background/Objectives: Osteoarthritis is a feature of the aging process. Here, we adopted in silico 2D finite element modeling (FEM) for the simulation of diseased ankle joints. We delved into the influence of body weight intensity on the stress distribution caused by subchondral cysts imitating degenerative age-related arthritic changes. Methods: FEM was performed using virtually generated pictorial schemes of the ankle joint skeletal contour. It included a constellation of scenarios with solitary or multiple cysts, or the lack thereof, located centrally, peripherally, or both in the talus and tibia at increased fixed levels of body weight. Results: The modeling showed that the highest stress was in the presence of a solitary central cyst in the talus and two centrally located cysts in the talus and the tibia, with the averaged values of 1.81 ± 0.52 MPa and 1.92 ± 0.55 MPa, respectively; there was a significant increase compared with the 1.24 ± 0.35 MPa in the control condition without cysts. An increase in body weight consistently increased the strain on the ankle joint. In contrast, peripherally located cysts failed to affect the stress distribution significantly. Conclusions: We conclude that subchondral central cysts substantially enhance the stress exerted on the ankle joint and its vicinity with body weight dependence. FEM’s ability to predict the location and magnitude of subchondral stress changes when confirmed in clinical trials might help to optimize the management of age-related degenerative joint changes. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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Review

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30 pages, 650 KiB

Open AccessReview

Molecular Mechanisms and Therapeutic Role of Intra-Articular Hyaluronic Acid in Osteoarthritis: A Precision Medicine Perspective

by Wojciech Glinkowski, Dariusz Śladowski, Wiesław Tomaszewski and Pol-IAHA Study Group

J. Clin. Med. 2025, 14(8), 2547; https://doi.org/10.3390/jcm14082547 - 8 Apr 2025

Viewed by 771

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and pain, which leads to significant disability. IAHA is widely used because of its viscoelastic properties, which restore synovial fluid homeostasis and reduce symptoms. However, emerging evidence suggests that IAHA exerts additional biological effects including chondroprotection, inflammatory modulation, oxidative stress reduction, and pain modulation, which may influence disease progression. Objective: This narrative review examines the biological mechanisms underlying IAHA’s role in OA management. The review explored IAHA’s effects on synovial fluid viscoelasticity, inflammatory cytokine modulation, cartilage preservation, oxidative stress regulation, and pain pathways, emphasizing the influence of molecular weight variations on therapeutic efficacy. Additionally, this review evaluates IAHA’s integration into multimodal treatment strategies, its potential disease-modifying effects, and future directions for personalized treatment approaches. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, EMBASE, Scopus, and Web of Science for studies published between January 2000 and March 2024. The search focused on IAHA’s molecular, cellular, and biochemical effects in OA and clinical findings assessing its impact on joint function, pain relief, and disease progression. Results: IAHA improves synovial fluid lubrication, reduces proinflammatory cytokines (IL-1β, TNF-α), inhibits matrix metalloproteinases (MMPs), scavenges reactive oxygen species (ROS), and modulates nociceptive pathways. High-molecular-weight IAHA demonstrates superior efficacy in advanced OA, while low-molecular-weight formulations may be better suited for early-stage disease. Although IAHA’s symptom relief is comparable to corticosteroids and NSAIDs, its favorable safety profile and emerging disease-modifying potential support its long-term use in OA management. Conclusions: IAHA represents a multifaceted therapeutic approach bridging symptomatic relief and regenerative strategies. While long-term efficacy, optimal administration protocols, and patient-specific responses remain subjects of ongoing research, refining treatment selection criteria, dosing regimens, and combination strategies may enhance clinical outcomes. Future studies should explore biomarker-driven approaches, standardize treatment protocols, and assess IAHA’s synergy with regenerative medicine to optimize its role in OA management. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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25 pages, 1168 KiB

Open AccessReview

Intra-Articular Hyaluronic Acid for Knee Osteoarthritis: A Systematic Umbrella Review

by Wojciech Michał Glinkowski and Wiesław Tomaszewski

J. Clin. Med. 2025, 14(4), 1272; https://doi.org/10.3390/jcm14041272 - 14 Feb 2025

Cited by 3 | Viewed by 2666

Abstract

Objective: to evaluate the efficacy, safety, and cost-effectiveness of intra-articular hyaluronic acid (IAHA) in treating osteoarthritis (OA), considering innovations in formulations, comparative outcomes, and variability in guidelines. This review aims to synthesize evidence supporting the role of IAHA in multimodal treatment strategies. Materials and Methods: A general, narrative, umbrella review of systematic reviews and meta-analyses was conducted. Clinical practice recommendations and guidelines for IAHA use were also reviewed and evaluated. A comprehensive search was conducted across the main medical data sources. Inclusion criteria focused on studies evaluating the efficacy, safety, and impact of IAHA. Key outcomes included pain reduction (e.g., WOMAC, VAS), functional improvement, safety, and cost-effectiveness. Results: IAHA showed moderate efficacy in pain relief and functional improvement, especially in early-to-moderate OA. The results indicate that hybrid formulations and combination therapies show better clinical outcomes, with expanded efficacy and potential chondroprotection. However, heterogeneity between studies was noted, reflecting variability in patient populations and intervention protocols. International guidelines varied significantly, with some opposing routine use (e.g., AAOS, NICE) and others endorsing IAHA more or less conditionally (e.g., ESCEO, OARSI). Conclusions: IAHA remains a treatment modality in the arsenal of selected populations of people with OA, especially for early and moderate disease. High-quality, standardized studies are still needed to refine IAHA’s role and establish personalized guidelines for individual patients. A concerted effort to harmonize global recommendations and economic strategies, such as tiered pricing, can increase equitable access and optimize IAHA’s integration of multimodal treatment for OA. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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15 pages, 835 KiB

Open AccessReview

Harnessing the Power of Water: A Scoping Review of Hydrokinesiotherapy as a Game-Changer in Knee Osteoarthritis Management

by Roberto Tedeschi, Federica Giorgi and Danilo Donati

J. Clin. Med. 2024, 13(19), 5811; https://doi.org/10.3390/jcm13195811 - 28 Sep 2024

Cited by 2 | Viewed by 2466

Abstract

Background: Knee osteoarthritis (OA) is a prevalent condition that significantly impairs pain, mobility, and quality of life. Hydrokinesiotherapy, a water-based exercise therapy, is gaining traction as a potential alternative to traditional land-based rehabilitation for managing knee OA symptoms. Methods: This scoping review aimed to evaluate the effectiveness of hydrokinesiotherapy compared to standard land-based physical therapy and self-administered exercise regimens in improving pain, joint mobility, quality of life, and physical function in patients with knee OA. Five randomized controlled trials (RCTs) were included, assessing outcomes using measures such as the WOMAC score, Visual Analog Scale (VAS), and SF-12. The studies were critically appraised using the PEDro scale and the RoB-2 tool to determine the quality and risk of bias. Results: Hydrokinesiotherapy consistently demonstrated superior outcomes in pain reduction, joint mobility, and physical function across all studies. Patients in the hydrokinesiotherapy groups reported significant improvements in pain and mobility, which were strongly associated with enhanced quality of life. The review also highlighted the potential for hydrokinesiotherapy to serve as an effective alternative or complement to land-based exercises, particularly in populations experiencing severe symptoms. Conclusions: Hydrokinesiotherapy is an effective intervention for managing knee OA, offering significant improvements in key clinical outcomes. Given its benefits, hydrokinesiotherapy should be considered a valuable addition to knee OA treatment protocols. However, further research is needed to confirm long-term effects and to explore ways to improve accessibility to this therapeutic option. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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Other

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14 pages, 4116 KiB

Open AccessSystematic Review

Efficacy and Safety of Celecoxib and a Korean SYSADOA (JOINS) for the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis

by Yong-Beom Park and Jun-Ho Kim

J. Clin. Med. 2025, 14(4), 1036; https://doi.org/10.3390/jcm14041036 - 7 Feb 2025

Viewed by 1116

Abstract

Background: The efficacy of cyclooxygenase-2 (COX-2) inhibitors, including celecoxib, in managing knee osteoarthritis (KO) is well-established. Recently, the plant extract cocktail JOINS (SKI306X and its newer formulation, SKCPT) has been shown to be an effective slow-acting drug for KO. Aims: To compare the efficacy and safety of celecoxib and JOINS in patients with KO. Methods: A systematic search of the MEDLINE, Embase, and Cochrane Library databases identified randomized controlled trials (RCTs) assessing the effectiveness and safety of celecoxib and JOINS. The outcomes included pain relief, functional improvement, and safety profiles. Outcome measurements were compared between the celecoxib and JOINS cohorts at the short-term (closest to 3 months) and mid-term (closest to 12 months). Results: Overall, 23 RCTs involving 3367 patients were included in this systematic review. The efficacy of JOINS in reducing pain, as indicated by the visual analog scale (VAS) score, was comparable to that of celecoxib. Regarding functional improvement assessed using the Western Ontario and McMaster University Arthritis Index (WOMAC), JOINS showed improvement comparable to that of celecoxib regardless of follow-up. In addition, no significant difference was observed in the incidence of adverse events between the celecoxib and JOINS cohorts. Conclusions: The results of this study suggest that JOINS could be considered as a pharmacological agent with significant efficacy for pain relief and functional improvement in patients with KO in clinical practice. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

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