Search Results (4,421)

Background: Reports on subchondral bone mechano-structure in individuals with various stages of knee osteoarthritis (KOA) are limited and often conflicting in contemporary literature. Our study aimed to assess differences in subchondral trabecular bone mechano-structure across late KOA stages in a homogenous group of patients with varus malalignment (confirmed by negative hip-knee-ankle-angle values). Methods: This retrospective cross-sectional study included micro-computed tomography scanning and Vickers micro-hardness testing of 90 bone samples (30 femoral and 60 tibial) collected from 15 adult patients with primary KOA undergoing total knee arthroplasty (TKA). The Kellgren–Lawrence grading system was used to assess the severity of KOA lesions in the included individuals, and bone samples were divided into the following groups: moderate KOA (42 samples from seven patients, age: 70 ± 7 years, females: 3/7) and end-stage KOA (48 samples from eight patients, age: 70 ± 6 years, females: 5/8). Results: Our data revealed site-specific sclerotic alterations in subchondral trabecular bone mechano-structure (thicker trabeculae, coupled with higher bone mineral content and increased bone micro-hardness) in individuals with end-stage KOA compared to moderate KOA, supporting its role in KOA pathogenesis beyond the exclusive cartilage degeneration effect. Our data also revealed that most heterogeneous subchondral trabecular mechano-structure was present in bone samples obtained from the medial part of the tibial and femoral condyle, revealing the substantial effect of mechanical loading during varus knee malalignment. Conclusions: Observed site-specific alterations in subchondral bone mechano-structure in individuals with end-stage KOA supported the role of subchondral sclerosis in primary KOA pathogenesis beyond its exclusive effect on cartilage degeneration. Full article

Osteoarthritis (OA) remains an alarming therapeutic challenge, as conventional intra-articular interventions primarily address symptomatic relief without halting progressive cartilage and bone degeneration. In this study, we investigated the disease-modifying potential of Cyclo(His-Pro) (CHP) in a monosodium iodoacetate (MIA)-induced OA rat model. Intra-articular CHP yielded significant clinical improvements, reducing joint edema and reversing OA-induced mechanical and thermal hypersensitivity, as evidenced by lifting behavior, rotarod performance, and hot plate tests. Beyond analgesia, micro-computed tomography (micro-CT) analysis showed that CHP preserved subchondral bone architecture, restoring trabecular volume and thickness and reducing serum C-terminal telopeptide of type II collagen (CTX-2), indicative of suppressed cartilage degradation. At the molecular level, CHP reprogrammed the joint microenvironment by suppressing Cox2, Adamts5, Mmp13, Mmp1, Mmp2, and Timp2 expression and decreasing systemic prostaglandin E2 (PGE₂) levels. Moreover, CHP showed efficacy comparable to Conjuran, a polynucleotide-based mechanical supportive agent, while additionally targeting COX-2/PGE₂-driven inflammatory cascades and cartilage catabolic pathways. Collectively, these findings indicate that intra-articular CHP confers combined analgesic, chondroprotective, and osteoprotective effects, supporting its potential as a promising disease-modifying osteoarthritis drug candidate. Full article

As the population ages, the incidence and prevalence of musculoskeletal degeneration, such as osteoarthritis, increase. While the currently accepted treatment options provide symptomatic and functional improvement, they do not halt the progression of osteoarthritis. This results in the eventual need for surgery for many patients with advanced osteoarthritis. Due to the seemingly inevitable progression of OA, many clinicians and researchers have shifted their focus to regenerative therapies. Orthobiologics, a specific type of regenerative therapy designed to treat orthopedic conditions, has been gaining traction in recent years due to the utilization of autologous biological substances and synthetic peptides in healing musculoskeletal injuries and degenerative conditions. Orthobiologics can be distinguished into one of four classes: cell-based, biologic fluids-based, matrix-based, molecular-based, and based on their composition. In this review, key examples of each class, mechanism of action, and current clinical data for each agent are examined. Limitations of current orthobiologics involve a lack of standardization in the preparation and administration of each agent, as well as uniformity in assessment endpoints across different clinical studies. Lastly, we will discuss future directions of orthobiologics as a therapy for the treatment of osteoarthritis. Full article

Background: Total knee arthroplasty in patients with hemophilia remains the most effective surgical intervention for end-stage hemophilic arthropathy, yet it poses unique surgical and perioperative challenges that are rarely encountered in standard osteoarthritis cases. This article synthesizes technical, anatomical, and perioperative considerations specific to hemophilic patients and integrates prospective clinical data derived exclusively from the hemophilic cohort of our long-term study (twenty patients, twenty knees; 2015–2024). Emphasis is placed on deformity correction, bone loss management, implant selection, hemostatic strategies, transfusion patterns, and perioperative pitfalls. The objective is to provide a comprehensive narrative reference for surgeons managing complex hemophilic knees, consolidating both evidence-based recommendations and practical perioperative “tips and tricks” accumulated across more than a decade of clinical experience. Methods: This prospective observational study evaluated twenty consecutive male patients with hemophilia who underwent primary total knee arthroplasty for advanced hemophilic arthropathy between 2015 and 2024 at our institution. The following variables were collected: operative time measured from skin incision to skin closure, postoperative transfusion requirement, length of hospitalization measured in days, early postoperative complications, and functional recovery as assessed by the Knee Society Score. Early complications included postoperative bleeding or hematoma, superficial or deep infection, and stiffness requiring intensive physiotherapy or manipulation under anesthesia. Results: The mean age at the time of surgery was 44.8 years with a standard deviation of 7.2 years, ranging from 31 to 59 years. The mean operative time in the hemophilic cohort was 154.54 min with a standard deviation of 18.36 min. The range of operative time was from 120 to 180 min. Nine of the twenty patients, representing 45 percent, required postoperative blood transfusion. The mean length of hospital stay in the hemophilic cohort was 12.3 days with a standard deviation of 2.38 days, ranging from 9 to 17 days. The mean Knee Society Score improved from 38 points preoperatively to 82 points at final follow-up, representing a mean increase of 44 points. Conclusions: Total knee arthroplasty in hemophilic patients is safe and effective when specialized surgical techniques, comprehensive synovectomy, precise deformity correction, optimized hemostasis, and structured postoperative coagulation factor replacement are implemented. Functional outcomes and prosthetic survival are excellent in experienced centers. Full article

Background/Objective: Osteoarthritis (OA) is the most common indication for total hip arthroplasty (THA), yet postoperative utilization and discharge outcomes vary substantially due to heterogeneous comorbidity burdens. This study applied unsupervised machine learning clustering to identify distinct comorbidity profiles among OA patients undergoing THA and to evaluate their association with non-routine discharge (NRD) and length of stay (LOS). Methods: The 2015–2021 National Inpatient Sample was queried using ICD-10 CM/PCS codes to identify patients with OA undergoing THA. Forty-nine comorbidities, complications, and in-hospital clinical covariates were incorporated into a k-modes clustering analysis. The Davies–Bouldin and Calinski–Harabasz indices were used to determine the optimal number of clusters. Multivariable logistic regression assessed adjusted odds of NRD across clusters, and Kruskal–Wallis H testing evaluated differences in LOS. Results: A total of 401,846 patients were included, and five distinct clusters were identified, ranging from 777 to 331,755 patients. Clusters with higher prevalence of renal dysfunction, cardiovascular disease, anemia, and heart failure demonstrated significantly increased risk of NRD (adjusted odds ratios up to 3.01, p < 0.001) and prolonged hospitalization, with median LOS up to 4 days. Lower-risk clusters exhibited shorter hospitalizations with median LOS of 2 days and higher rates of routine discharge. Kruskal–Wallis testing confirmed significant LOS differences across all clusters (p < 0.001). Conclusions: Machine learning clustering of OA patients undergoing THA identified clinically distinct subgroups with graded differences in postoperative hospital utilization. Patients with greater comorbidity burden experienced disproportionately higher risk of NRD and prolonged LOS. This data-driven framework highlights heterogeneity within the OA population and may inform future strategies for perioperative risk stratification and resource planning. Full article

Alkaptonuria (AKU) is a rare inherited metabolic disorder characterized by progressive musculoskeletal damage, chronic pain, and functional heterogeneity. To better quantify this variability, we introduced the concept of the functional age gap, defined as the difference between chronological age and a data-derived estimate of functional age. The study included 134 patients with AKU from the ApreciseKUre database. Functional age was calculated by mapping Health Assessment Questionnaire Disability Index (HAQ-DI) and Knee Injury and Osteoarthritis Outcome Score (KOOS) values to age-referenced normative data. Most patients (94.8%) showed a positive functional age gap, with a mean difference of 15 years, which indicates a functionally older profile than expected for their chronological age. A bagging ensemble of decision trees was then used to explore relationships between clinical variables and functional age gap severity. The model achieved moderate but stable classification performance across repeated stratified cross-validation (64%), consistent with an exploratory analysis in a small rare-disease cohort. SHapley Additive exPlanations analysis identified age, AKUSSI spinal pain, AKUSSI joint pain, Schober test, and hip and knee activity as the most influential predictors. These findings support the functional age gap as an interpretable, hypothesis-generating descriptive metric for functional assessment in AKU, while its predictive utility for individual patient stratification will require validation in larger and longitudinal cohorts. Full article

This study aimed to evaluate the therapeutic effects of platelet-rich plasma (PRP) and Cervus and Cucumis polypeptide (CCP) injections in rats with post-traumatic osteoarthritis (OA). The model was established by transection of the anterior cruciate ligament, and the animals were subsequently treated with PRP and CCP. Articular cartilage degeneration was assessed through gross morphological observation, histopathological staining, and a standardized scoring system. Concurrently, pain-related behaviors, joint swelling, levels of inflammatory cytokines, and markers associated with extracellular matrix degradation were measured. The results demonstrated that, compared with the OA model group, PRP and CCP exhibited varying degrees of functional improvement, specifically, a reduction in pain-related behaviors and an alleviation of joint swelling. Furthermore, cartilage morphological damage was diminished, inflammatory marker levels decreased, and indicators of extracellular matrix degradation were attenuated. Histopathological examination of liver and kidney tissues revealed no apparent abnormalities. This study provides valuable experimental evidence for further treatment strategies for OA. Full article

Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial degenerative disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation, leading to pain and functional impairment in affected individuals. Despite its clinical impact, effective disease-modifying treatments remain limited, highlighting the need for innovative therapeutic approaches for treating this condition in the future. This manuscript examines the biological rationale, clinical applications, and therapeutic potential of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) in the management of TMJ-OA. As autologous platelet-derived biomaterials, PRP and i-PRF contain high concentrations of growth factors and bioactive molecules that can modulate inflammatory responses and support tissue repair. PRP is associated with a relatively rapid release of these mediators, whereas i-PRF forms a fibrin matrix that may enable a more sustained release profile. Current clinical evidence suggests that both therapies show potential to contribute to pain reduction and may facilitate improvements in mandibular function. However, substantial heterogeneity in preparation protocols, study designs, and outcome measures limits the comparability and generalizability of these findings to the general population. Overall, PRP and i-PRF represent promising, minimally invasive regenerative strategies for managing TMJ-OA. Full article

Computed tomography (CT) is used to support the diagnosis of equine temporomandibular joint (TMJ) disease; however, its diagnostic accuracy remains unclear. This study aimed to evaluate the relationship between CT findings and histopathological manifestations of osteoarthritis (OA) in equine TMJs. A total of 82 TMJs were CT-imaged, sampled, grouped into age-related and OA-related groups, and analyzed for frequency distributions, correlations, and CT-based TMJ OA diagnosis. CT findings were observed in 79% of joints, including ‘CT anatomical variations’ considering to reflect age-related remodeling. Only 50% of joints showed co-occurrence of CT findings and histopathological manifestations of OA, confirming that not all CT findings are indicative of disease. Including all CT findings in the CT-based diagnosis of TMJ OA yielded a specificity of 0.41 (95% CI: 0.26–0.58), suggesting a high rate of false-positive diagnoses. Excluding all ‘CT anatomical variations’ resulted in a sensitivity of 0.56 (95% CI: 0.40–0.72), indicating a substantial number of false-negative diagnoses. However, inclusion of specific ‘CT anatomical variation’—subchondral bone cysts—into the studied CT-based diagnosis increased sensitivity to 0.79 (95% CI: 0.62 to 0.89) while maintaining high specificity of 0.92 (95% CI: 0.80–0.98). Including this subset of CT findings in the diagnosis of equine TMJ OA may improve the accuracy of disease detection; however, the clinical relevance of the present cadaver investigation needs to be confirmed in in vivo studies. Full article

Background and Clinical Significance: Tannerella forsythia is a Gram-negative, anaerobic bacterium primarily associated with severe periodontal disease. Extraoral infections are extremely rare, and the presence of Tannerella forsythia in synovial fluid has not been reported previously. Case Presentation: We report a case of a 60-year-old female with grade IV primary osteoarthritis referred for dental evaluation. Clinical and radiographic examination revealed stage IV generalized periodontitis. Subgingival plaque samples were collected after non-surgical periodontal therapy and analyzed using a semi-quantitative real-time PCR targeting the 16S rRNA gene. During planned knee surgery, synovial fluid was obtained and processed using the same molecular protocol. PCR analysis of samples from the deepest periodontal pockets and synovial fluid confirmed the presence of Tannerella forsythia, demonstrating its potential dissemination from oral to joint tissues. The postoperative course was uneventful, with no signs of joint infection. Conclusions: To the best of our knowledge, this is the first reported detection of Tannerella forsythia in the synovial fluid of a patient with osteoarthritis, supporting the possibility of oral–joint microbial translocation. This finding should be interpreted with caution, as the detection of bacterial DNA does not indicate viability or causative involvement. More research is necessary to clarify the mechanisms underlying this association. Full article

Osteoarthritis (OA) severity grading from hand distal interphalangeal (DIP) joint radiographs using the Kellgren–Lawrence (KL) scale is challenged by severe class imbalance, with higher grades (KL3 and KL4) markedly underrepresented in clinical datasets. To address this limitation, we propose a VGG19-based classification framework that systematically evaluates six training strategies targeting imbalance at the data level, algorithmic level, or in combination. Synthetic images for minority classes were generated using CycleGAN and subsequently filtered through rheumatologist validation. The evaluated strategies include baseline training, rheumatologist-validated synthetic augmentation (SD), oversampling (OS), focal loss (FL) optimization, and multiple combinations of these approaches. The results show that strategies incorporating oversampling demonstrated the most consistent and statistically robust improvements in minority-class performance. Specifically, the combination of synthetic data and oversampling (SD + OS) achieved the highest binary OA sensitivity (96.12%) and significantly improved OA F1 score compared to baseline (0.613 vs. 0.416, p = 0.029). The full combined strategy (SD + OS + FL) yielded the highest KL3 F1 score (0.527 vs. 0.280 baseline, p = 0.048) and significantly improved KL4 F1 score (0.730 vs. 0.570 baseline, p = 0.150). Importantly, all strategies maintained higher or similar overall performance with no significant change in majority-class performance (p > 0.10), indicating that improvements in minority classes were not achieved at the expense of sacrificing majority classes or overall model reliability. These findings suggest that the proposed imbalance-mitigation strategies may improve minority class OA detection, particularly when oversampling and validated synthetic augmentation are combined. It is worth noting that the above results are derived from a held-out test set comprising 1626 samples, among which only 43 are OA-positive due to data imbalance. The results should be treated as preliminary findings subject to change upon validation in larger cohorts of OA patients. Full article

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative joint disease that affects quality of life through pain, impaired functional performance, and altered gait patterns. Hydrotherapy is a well-tolerated form of physical rehabilitation, especially suitable for patients with severe pain, as water’s properties support movement while reducing joint load. Its effects have been widely studied, primarily focusing on patient-reported outcomes, with limited synthesis of functional performance and gait-related outcomes. Materials and Methods: A systematic search was conducted in PubMed, Web of Science, Cochrane, PEDro, SpringerLink, ScienceDirect, and Google Scholar, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy included a combination of Medical Subject Headings (MeSH) terms and keywords. For example, the PubMed search strategy was as follows: (“knee osteoarthritis” OR “knee OA”) AND (“hydrotherapy” OR “aquatic therapy” OR “water-based exercise”) AND (“gait” OR “walking” OR “functional performance”). Randomized controlled trials (RCTs) from the last 10 years involving patients with KOA undergoing aquatic therapy were included. Primary outcomes included functional performance assessed by measures such as the 6 min walking test (6MWT), the Timed Up and Go (TUG) test, the five sit-to-stand (5 STS) and stair climb (SC) tests, and by using gait-related parameters (e.g., speed, cadence, and step length) assessed clinically or using technology. Patient-reported outcomes, including the Visual Analog Scale (VAS), Western Ontario and McMaster University’s Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS), were analyzed as a secondary objective. Results: A total of 479 studies were identified, of which 13 met the eligibility criteria. The results revealed improvements in functional performance, with increases in 6MWT in five studies, the TUG test in four trials, and better performance in the 5-STS and SC tests in five studies. Benefits in gait parameters were noted in four studies. Additionally, one of the articles reported improvements in static and dynamic balance, another showed enhanced proprioception, and a third described more efficient muscle activation during gait following hydrotherapy. Consistent benefits in pain reduction, joint stiffness, and activities of daily living, as reflected by VAS, WOMAC, and KOOS, were also noted immediately and maintained at follow-up. The variability in outcome measures and intervention characteristics limited the possibility of data integration and the calculation of effect sizes. Conclusions: Hydrotherapy as a rehabilitation intervention may be associated with improvements in functional capacity, mobility, and self-reported physical ability in patients with KOA, with some evidence supporting a beneficial effect on gait; however, the certainty of evidence remains low to moderate due to heterogeneity among studies and limited sample sizes. These findings should be interpreted in light of the methodological limitations identified across the included trials. Full article

Osteoarthritis (OA) is a multifactorial degenerative joint disease characterized by chronic inflammation, progressive cartilage extracellular matrix (ECM) degradation, and impaired joint lubrication, creating a complex pathological microenvironment that remains challenging to treat. In this study, a glycosaminoglycan (GAG)-mimetic sulfated chitosan (SCS) was synthesized via chemical modification of chitosan by grafting sulfonic acid groups, aiming to address these pathological features simultaneously. The therapeutic potential of SCS in OA was systematically evaluated. In vitro results demonstrated that SCS significantly promoted ECM synthesis in chondrocytes. Tribological analysis further revealed that SCS effectively enhanced cartilage lubrication in OA porcine cartilage, as evidenced by a marked reduction in the coefficient of friction, which decreased by 19% under a 5 N load and by 30% under a 10 N load. PCR analysis showed that SCS treatment significantly upregulated chondrogenic-related genes. In addition, SCS exhibited pronounced anti-inflammatory effects by downregulating the expression of inflammatory and catabolic genes. Importantly, in vivo studies demonstrated that SCS effectively preserved cartilage ECM and alleviated synovitis. Collectively, these findings indicate that SCS can simultaneously promote cartilage matrix regeneration, improve lubrication, and suppress inflammation, thereby effectively alleviating OA progression in a complex pathological environment. This study highlights the potential of SCS as a multifunctional GAG-mimetic biomaterial for osteoarthritis therapy. Full article

The crystal arthropathies gout and calcium pyrophosphate deposition (CPPD) disease represent a significant subset of rheumatic and musculoskeletal diseases, yet their overlap with common entities such as osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains underrecognized. We conducted a structured narrative review of studies published through August 2025, exploring the epidemiology, clinical presentation, imaging characteristics, and treatment implications of these overlapping conditions. We particularly examine how crystal deposition may mimic or complicate the clinical course of OA, RA, and PsA, especially in older adults with multimorbidity. Recognizing these overlaps is critical to avoid misdiagnosis, inappropriate escalation of immunomodulatory therapy, and missed opportunities for targeted crystal-directed treatment. Full article

Obesity is a complex, heterogeneous, chronic, and progressive disease, which correlates with an augmented risk of developing several comorbidities, including painful conditions, such as osteoarthritis. In this review, authors present for the first time the term meta-neuroinflammation for describing how the chronic, low-grade systemic inflammation, that occurs in obesity, may trigger oxidative stress and neuroinflammatory processes. Both the peripheral and the central nervous system are involved in neuroinflammation, leading to central sensitization and pain chronification, which leads to the observed increased incidence in obese patients of chronic pain syndromes, particularly osteoarthritis, low back pain, fibromyalgia, headache, and diabetic peripheral neuropathy. Possible mechanisms by which obesity may cause meta-neuroinflammation include adiposopathy, gut microbiota dysbiosis, and compromised integrity of blood–brain barrier, which could explain obesity-related depressive and neurodegenerative disorders. Preclinical data suggest the meta-neuroinflammation as a potential target of treatment in obese patients with degenerative joint disease. Based on these observations, targeted therapeutic strategies may include systemic administration of ultramicronized palmitoylethanolamide (um-PEA), well known for its neuroprotective, anti-neuroinflammatory, and analgesic actions, and comicronized PEA–rutin and hydroxytyrosol to restore intestinal eubiosis, with beneficial effects on body weight and mental disorders. Finally, Adelmidrol, as a PEA congener, could be considered for mitigating intra-articular meta-neuroinflammation in knee osteoarthritis. Full article