Joint Osteoarthritis Research Articles

Synovial osteoclastogenesis mediated by chondrocyte-secreted TNFα promotes TMJ condylar resorption.

Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. Invitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. Invitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

FIVE-YEAR OUTCOMES OF A SYNTHETIC CARTILAGE IMPLANT FOR THE FIRST METATARSOPHALANGEAL JOINT IN ADVANCED HALLUX RIGIDUS

Introduction/PurposeA randomized clinical trial of first MTP joint hemiarthroplasty with a synthetic cartilage implant demonstrated equivalent pain, function and safety outcomes to first MTP joint arthrodesis at 2 years. Recognizing that many hemiarthroplasty and total toe implants have initially good results that deteriorate over time, the purpose of this study was to prospectively assess the safety and efficacy outcomes for the synthetic cartilage implant population and to determine if the excellent outcomes were maintained at >5 years.MethodsOne hundred nineteen patients were evaluated at 5+ years; 23 could not be reached for follow-up, but implant status was available for 7 of these subjects. Patients completed a pain visual analogue scale (VAS) and Foot and Ankle Ability Measure (FAAM) Sports and Activities of Daily Living (ADL) scores, preoperatively and at 2, 6, 12, 26, 52, 104 and 260 weeks postoperatively. Minimal clinically important differences are: ≥30% difference for pain VAS, 9 points for FAAM Sports, and 8 points for FAAM ADL. Great toe active dorsiflexion, weight-bearing radiographs, secondary procedures, and safety parameters were evaluated.ResultsOf 119 patients available at mean 5.8 years follow-up (SD ±0.7; range: 4.4–8.0), 9 underwent implant removal and conversion to fusion in years 2–5, leaving 106 patients. The implant survival rate was 92.4% at 5.8 years. Pain and function outcomes at 5.8 years were similar to those at 2 years. VAS Pain, FAAM Sports, ADL Scores were maintained or improved at 5.8 years. No evidence of avascular necrosis, device migration or fragmentation was observed. There were no unanticipated safety events through 5.8 years. Ninety-three (93%) percent would have the procedure again.ConclusionThe synthetic cartilage hemiarthroplasty implant continues to demonstrate safety and efficacy for the treatment of advanced first MTP joint osteoarthritis with evidence of therapeutic effect and acceptable safety profile at 5.8 years.

Osteoarthritis of zygapophysial joints as a cause of back pain and neck pain: a scoping review.

Zygapophysial joints (Z joints) can be a source of back pain and of neck pain, but the cause of pain is not known. Some authors attribute the pain to osteoarthritis but without citing evidence. The present review was undertaken to determine if there was sufficient evidence of association between spinal pain and osteoarthritis of Z joints to justify osteoarthritis being held to be the cause of pain. The null hypothesis was that osteoarthritis of Z joints does not cause back pain or neck pain. Relevant studies were ones that provided primary data on the association between pain and osteoarthritis of Z joints. These could be population studies, diagnostic studies, or case-control studies. The database of PubMed was searched using the terms: Lumbar or cervical, zygapophysial or facet, pain, and osteoarthritis or degeneration or degenerative. Data pertinent to the research question were extracted from original articles and tabulated for reporting. Odds ratios for associations were calculated, as were the prevalence rates of osteoarthritis in subjects with pain, and conversely the prevalence rates of pain in subjects with osteoarthritis. The searches retrieved 11 population studies, 4 diagnostic studies, and 3 cases control studies. No study showed any positive association between osteoarthritis of Z joints and pain. All studies found pain to be independent of the presence or severity of osteoarthritis. Osteoarthritis was as common in subjects with no pain as in subjects with pain. The null hypothesis was not refuted. The published evidence does not support the belief that osteoarthritis causes Z joint pain. All the evidence contradicts this belief.

Site-specific elastic and viscoelastic biomechanical properties of healthy and osteoarthritic human knee joint articular cartilage

Articular cartilage exhibits site-specific biomechanical properties. However, no study has comprehensively characterized site-specific cartilage properties from the same knee joints at different stages of osteoarthritis (OA).Cylindrical osteochondral explants (n = 381) were harvested from donor-matched lateral and medial tibia, lateral and medial femur, patella, and trochlea of cadaveric knees (N = 17). Indentation test was used to measure the elastic and viscoelastic mechanical properties of the samples, and Osteoarthritis Research Society International (OARSI) grading system was used to categorize the samples into normal (OARSI 0–1), early OA (OARSI 2–3), and advanced OA (OARSI 4–5) groups.OA-related changes in cartilage mechanical properties were site-specific. In the lateral and medial tibia and trochlea sites, equilibrium, instantaneous and dynamic moduli were higher (p < 0.001) in normal tissue than in early and advanced OA tissue. In lateral and medial femur, equilibrium, instantaneous and dynamic moduli were smaller in advanced OA, but not in early OA, than in normal tissue. The phase difference (0.1–0.25 Hz) between stress and strain was significantly smaller (p < 0.05) in advanced OA than in normal tissue across all sites except medial tibia.Our results indicated that in contrast to femoral and patellar cartilage, equilibrium, instantaneous and dynamic moduli of the tibia and trochlear cartilage decreased in early OA. These may suggest that the tibia and trochlear cartilage degrades faster than the femoral and patellar cartilage. The information is relevant for developing site-specific computational models and engineered cartilage constructs.

Computer-simulated TOUCH prosthesis cup malposition and solutions

IntroductionTotal joint replacement has become significantly more common as a treatment for advanced trapeziometacarpal joint osteoarthritis in recent years. The latest generation of prostheses with dual-mobility designs leads to very good functional results and low rates of loosening and dislocation in the short and medium term. Biomechanical studies showed that central placement and parallel alignment of the cup with respect to the proximal articular surface of the trapezium are crucial for both cup stability and prevention of dislocation. Despite correct positioning of the guidewire, incorrect placement or tilting of the inserted cup may occur, requiring immediate intraoperative revision. MethodsThe existing spherical and conical cup models in sizes 9 mm and 10 mm were transferred to a computer-aided design dataset. Depending on the intraoperative complication (tilting or incorrect placement), the revision options resulting from the various combinations of cup type and size were simulated and analyzed according to the resulting defect area and bony contact area. ResultsIn well centered cups, a size 9 conical cup could be replaced by a size 9 spherical cup and still be fixed by press-fit. Conversely, a size 9 spherical cup could not be replaced by a size 9 conical cup, but only by a size 10 cup, of whatever shape. When a size 9 conical cup was tilted up to 20°, the best revision option was to resect the sclerotic margin and insert a size 10 conical cup deeper into the cancellous bone, to achieve the largest contact area with the surrounding bone. When a size 9 cup of whatever shape was poorly centered (misplaced with respect to the dorsopalmar or radioulnar line of the trapezium), placement should be corrected using a size 10 cup, combined with autologous bone grafting of the defect. Again, the size 10 conical cup showed the largest bony contact area. ConclusionOur computer-based measurements suggested options for intraoperative cup revision depending on cup shape and size and on type of misalignment with resulting bone defects. These suggestions, however, need to be confirmed in anatomic specimens before introducing them into clinical practice.

High frequency of BCP, but less CPP crystal-mediated calcification in cartilage and synovial membrane of osteoarthritis patients

ObjectiveEctopic articular calcification is a common phenomenon of osteoarthritic joints, and closely related with disease progression. Identification of the involved calcium crystal types represents an important topic in research and clinical practice. Difficulties in accurate detection and crystal type identification have led to inconsistent data on the prevalence and spatial distribution of BCP and CPP deposition. MethodCombining multiple imaging methods including conventional radiography, histology and Raman spectroscopy, this study provides a comprehensive analysis of BCP and CPP based calcification, its frequency and distribution in cartilage and synovial membrane samples of 92 OA patients undergoing knee replacement surgery. ResultsConventional radiography showed calcifications in 35% of patients. Von Kossa staining detected calcified deposits in 88% and 57% of cartilage and synovial samples, respectively. BCP crystals presented as brittle deposits on top of the cartilage surface or embedded in synovial tissue. CPP deposits appeared as larger granular needle-shaped clusters or dense circular pockets below the cartilage surface or within synovial tissue. Spectroscopic analysis detected BCP crystals in 75% of cartilage and 43% of synovial samples. CPP deposition was only detected in 18% of cartilage and 15% of synovial samples, often coinciding with BCP deposits. ConclusionBCP is the predominant crystal type in calcified cartilage and synovium while CPP deposition is rare, often coinciding with BCP. Distinct and qualitative information on BCP and CPP deposits in joint tissues give rise to the speculation that different disease entities are involved that might need different treatment strategies.

Glutathione peroxidase 4 restrains temporomandibular joint osteoarthritis progression by inhibiting ferroptosis.

There are few effective therapeutic strategies for temporomandibular joint osteoarthritis (TMJOA) due to the unclear pathology and mechanisms. We aimed to confirm the roles of GPX4 and ferroptosis in TMJOA progression. ELISA assay was hired to evaluate concentrations of ferroptosis-related markers. The qRT-PCR assay was hired to assess gene mRNA level. Western blot assay and immunohistochemistry were hired to verify the protein level. CCK-8 assay was hired to detect cell viability. Human fibroblast-like synoviocytes (FLSs) were cultured to confirm the effects of GPX4 and indicated inhibitors, and further verified the effects of GPX4 and ferroptosis inhibitors in TMJOA model rats. Markers of ferroptosis including 8-hidroxy-2-deoxyguanosine (8-OHdG) and iron were notably increased in TMJOA tissues and primary OA-FLSs. However, the activity of the antioxidant system including the glutathione peroxidase activity, glutathione (GSH) contents, and glutathione/oxidized glutathione (GSH/GSSG) ratio was notably inhibited in TMJOA tissues, and the primary OA-FLSs. Furthermore, the glutathione peroxidase 4 (GPX4) expression was down-regulated in TMJOA tissues and primary OA-FLSs. Animal and cell experiments have shown that ferroptosis inhibitors notably inhibited ferroptosis and promoted HLS survival as well as up-regulated GPX4 expression. Also, GPX4 knockdown promoted ferroptosis and GPX4 overexpression inhibited ferroptosis. GPX4 also positively regulated cell survival which was the opposite with ferroptosis. In conclusion, GPX4 and ferroptosis regulated the progression of TMJOA. Targeting ferroptosis might be an effective therapeutic strategy for TMJOA patients in the clinic.

Characterization of the knee joint phenotype in the Portuguese population

Background: Neutral constitutional alignment and neutral joint line obliquity has been the standard alignment strategy for total knee arthroplasty. This one-for-all measure may negatively impact gait pattern and knee biomechanics. Novel alignment strategies surged, considering the variability in phenotypes found across the literature, as different populations may present different phenotype distributions. The Portuguese population has a distinct genetic origin, with no phenotype distribution data. Our objective was to characterise the population’s knee morphology, searching and analysing adjacent joint osteoarthrosis, and calculating the pre-disease coronal alignment. Methods: A retrospective cohort study was conducted. Full-length X-rays performed between 2016-2023 were analysed. Five alignment parameters were measured (LDFA, MPTA, JLCA, TJLA, HKA), and two parameters were calculated (aHKA, JLO). Knees were classified according to the CPAK classification. Results: For the arthritic cohort, CPAK-I (23%) II (20%) were most common, aHKA increases as KL increases (r=0.8352; p&lt;0.001). For the healthy, Type-II (42%) and Type-I (15%) were most common. For paediatric, Type-II (43%) and Type-V (21%) were most common. CPAK Types-VII/VIII/IX were rare. Differences between genders for healthy and arthritic cohorts were statistically significant. The arthritic had higher prevalence of adjacent joint osteoarthritis. Conclusions: The Portuguese population presents a similar knee phenotype comparing with other populations, some differences have been found regarding the Asian continent. The most common phenotype was a neutral alignment if either healthy or paediatric, or a varus alignment if knee OA. Coronal alignment may not have a major impact in the prevalence of ankle and hip osteoarthritis; however, higher prevalence is observed in patients with knee OA.

Some features of vitamin D content in arterial hypertension in patients with and without osteoarthritis of the knee joints

The aim of the study was to assess the relationship of serum vitamin D concentration with impaired cardiometabolic profile in hypertension in patients with and without osteoarthritis of the knee joints.Materials and methods. The results of the examination of 196 patients aged 54.06±9.4 years with arterial hypertension (AH) were analyzed, who were divided into groups depending on the presence of osteoarthritis of the knee joints (OA KS): 1st–patients with AH (n=153) and 2nd–patients with AH+OA KS (n=43).All patients were assessed for the level of 25 (OH) D, biochemical parameters of blood plasma (total cholesterol, low and high density lipoproteins, triglycerides, creatinine), cardiac morphometry using ECHOCG.Results. The proportion of people with adequate vitamin D levels was 1.2 times higher among patients with AH+OA CS (32.6 % vs. 26.1 %, p0.05). Additional vitamin D supplementation was significantly more common in the group of patients with AH+OA (0 % vs. 44 %, p&lt;0.001).The subgroup with vitamin D deficiency in patients with hypertension without OA CS had the most unfavorable «cardiometabolic» profile (they had significantly high BMI, total cholesterol, and LVH).Conclusions. In people with arterial hypertension (without OA CS), violations of vitamin D levels (deficiency or insufficiency) are associated with an unfavorable «cardio-metabolic» profile – they need additional testing of vitamin D levels in the blood and correction of the detected violations. The presence of pathology of the musculoskeletal system (OA CS) in patients with arterial hypertension, it had no effect on the level of vitamin D and the frequency of its individual disorders. However, in this cohort of patients (AH+OA), the use of vitamin D supplements was significantly more common (0 % vs. 44 %, p&lt;0.001). The assessment of the effect of vitamin D supplementation on cardiometabolic status deserves further investigation. Patients with arterial hypertension and its combination with comorbid pathology have, on average, vitamin D levels classified as insufficiency.

Hyaluronan-based hydrogel delivering glucose to mesenchymal stem cells intended to treat osteoarthritis

Mesenchymal stem cell (MSC) therapy shows promise in regenerative medicine. For osteoarthritis (OA), MSCs delivered to the joint have a temporal window in which they can secrete growth factors and extracellular matrix molecules, contributing to cartilage regeneration and cell proliferation. However, upon injection in the non-vascularized joint, MSCs lacking energy supply, starve and die too quickly to efficiently deliver enough of these factors. To feed injected MSCs, we developed a hyaluronic acid (HA) derivative, where glucose is covalently bound to hyaluronic acid. To achieve this, the glucose moiety in 4-aminophenyl-β-D-glucopyranoside was linked to the HA backbone through amidation. The hydrogel was able to deliver glucose in a controlled manner using a trigger system based on hydrolysis catalyzed by endogenous ß-glucosidase. This led to glucose release from the hyaluronic acid backbone inside the cell. Indeed, our hydrogel proved to rescue starvation and cell mortality in a glucose-free medium. Our approach of adding a nutrient to the polymer backbone in hydrogels opens new avenues to deliver stem cells in poorly vascularized, nutrient-deficient environments, such as osteoarthritic joints, and for other regenerative therapies.

Mid- and long-term clinical results of the Elektra and Moovis prosthesis for trapeziometacarpal joint replacement

BackgroundTotal joint arthroplasty as a surgical treatment option for trapeziometacarpal joint arthritis is recently revived. The aim of this study is to report on mid- and long-term results of the Elektra (single-mobility) and Moovis (dual-mobility) prosthesis for treatment of primary thumb carpometacarpal joint arthritis.MethodsIn this retrospective, monocentric, descriptive cohort study, 31 prostheses were evaluated that were implanted by a single surgeon in 26 patients between 2009 and 2019. Indication for surgery was trapeziometacarpal joint osteoarthritis (Eaton/Littler Stage II and III). Clinical and radiological follow-up was performed at a minimum of 24 months. The postoperative assessment included range of motion, pain, strength as well as functional scores (DASH, MHQ). Implant survival and complications were the primary endpoints.Results10 Elektra and 21 Moovis prostheses were implanted between 2009 and 2019 with a mean follow-up of 74.2 months in the Elektra and 41.4 months in the Moovis group. The average patients’ age at surgery was 64 years. Postoperative pain levels (VAS 0–10) were below 2 at rest and under stress in both groups. Grip/pinch strength and range of motion showed results comparable to the contralateral hand. Opposition was excellent with an average Kapandji index of 9.6 in both groups. Elektra achieved slightly better functional scores in the DASH and MHQ score. Satisfaction was high in both groups, and 96% of the patients would recommend the procedure. Metacarpophalangeal hyperextension > 15° was seen in 3 patients per group preoperatively and was corrected to < 5° post-surgery. 3 Elektra prostheses were revised due to cup loosening and dislocation for cup and/or neck replacement or secondary trapeziectomy. 1 Moovis prosthesis was revised with an exchange of the neck to a larger size due to restricted movement. After the mean follow-up of 7.9 years in Elektra and 3.5 years in MOOVIS, cumulative survival was 68.6% vs. 95.2%, respectively.ConclusionsIn this mid- to long-term retrospective analysis, total joint arthroplasty in primary trapeziometacarpal joint arthritis results in low pain levels, excellent mobility and clinical function. Patient satisfaction is overall high. While revision due to cup loosening occurred more often in patients with single-mobility implants, no cases of dislocation or loosening of components were observed in the dual-mobility group.Trial registrationThe study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Medical Faculty of Heidelberg University, reference number S-150/2020.

E045 Adherence to physiotherapy among patients with knee osteoarthritis in a rheumatology specialized care unit in Sri Lanka

Abstract Background/Aims Knee osteoarthritis is a degenerative joint disorder that has a significant impact on global health and healthcare resources. Non-pharmacological interventions play a vital role in the management of osteoarthritis, and their effectiveness relies on the patient’s active participation and adherence. But non-adherence to these interventions including physiotherapy has become a recognized problem across the globe. The extent of adherence to physiotherapy specifically in the Sri Lankan population with osteoarthritis has not been assessed to date. Methods This cross-sectional study was conducted at Rheumatology and Rehabilitation Hospital, Ragama, Sri Lanka recruiting 100 patients diagnosed with knee joint osteoarthritis according to the EULAR 2011 Recommendations. General Rehabilitation Adherence Scale (GRAS) was used to score the adherence level to center-based physiotherapy. Home-based physiotherapy adherence was measured using a 5-point scale. Demographic data also were assessed to determine the associations with adherence levels. Data were analysed by using the Statistical Package of Social Sciences (SPSS). Results The study population consisted of 93% females and 7% males. Center-based physiotherapy adherence according to the GRAS score revealed 53% had a high adherence rate while 8% found poorly adhered to. Of the highly compliant patients, the majority, 35.8% patients were within the 60-69 years age group and 35.8% were housewives. 37.7% were not having co-morbidities. 41.7% have reported a disease duration of 1-5 years. The majority complained that they had poor adherence due to other commitments (36%) followed by and lack of time (34%). The third common cause for the default was transport expenses (26%). 91% of patients had knowledge of home-based physiotherapy activities. Of them, 32% followed the exercise regime as advised and 13% continued it as far as possible. 17% were unable to engage in those at all. As reasons for noncompliance to home therapy, 35% of patients reported having a lack of time and 31% had poor motivation. None of the sociodemographic factors significantly correlated with center-based or home-based physiotherapy adherence. Conclusion The findings indicate that a significant proportion of patients demonstrated high adherence to center-based physiotherapy. Although a majority of patients had knowledge of home-based physiotherapy activities, only a portion followed the prescribed exercise regime. Addressing barriers such as time constraints, commitments, and transportation expenses is crucial. Future research should explore personalized approaches and innovative strategies to enhance engagement and overcome challenges to optimize physiotherapy adherence. Disclosure S.K. Ubhayasiri: None. D. Abeysinghe: None.

Eligibility for knee arthroplasty is associated with increased risk of acquired hallux valgus - a Mendelian randomized study

ObjectiveClinically, it has been found that patients undergoing knee replacement have a high incidence of concomitant hallux valgus. In this study, we analyzed whether patients with osteoarthritis who underwent surgery and those patient who did not have surgery had an increased risk of hallux valgus by Mendelian randomization and performed reverse causal analysis.DesignGenomewide association study (GWAS) data for osteoarthritis, categorized by knee arthritis with joint replacement, knee arthritis without joint replacement, hip arthritis with joint replacement, and hip arthritis without joint replacement.And acquired hallux valgus were downloaded for Mendelian randomized studies. MR analysis was performed using inverse variance-weighted (IVW), weighted median, and MR-Egger methods. MR-egger regression, MR pleiotropic residuals and outliers (MR-presso), and Cochran's Q statistical methods were used to evaluate heterogeneity and pleiotropy.ResultsThe IVW results indicate that, compared to healthy individuals, patients who meet the criteria for knee osteoarthritis joint replacement surgery have a significantly higher risk of acquired hallux valgus. There were no significant causal relationships found for the remaining results. No significant heterogeneity or multiplicity was observed in all the Mr analyses.ConclusionOur study supports the increased risk of acquired hallux valgus in patients eligible for knee replacement. There is necessary for clinicians to be concerned about the hallux valgus status of patients undergoing knee arthroplasty.

Toll-like receptor activation regulates the paracrine effect of adipose-derived mesenchymal stem cells on reversing osteoarthritic phenotype of chondrocytes.

The therapeutic efficacy of intra-articular mesenchymal stem cells (MSCs) injection for patients with osteoarthritis (OA) currently exhibits inconsistency, and the underlying mechanism remains elusive. It has been postulated that the immunomodulatory properties and paracrine activity of MSCs might be influenced by the inflammatory micro-environment within osteoarthritic joints, potentially contributing to this observed inconsistency. Adipose-derived MSCs (ADSCs) were isolated from SD rats and pre-treated with Toll-like receptor 3 (TLR3) agonist Poly I:C or Toll-like receptor 4 (TLR4) agonist LPS. The pre-treated ADSCs were then co-cultured with IL-1β-induced osteoarthritic chondrocytes using a Transwell system to analyze the paracrine effect of ADSCs on reversing the osteoarthritic phenotype of chondrocytes. RT-PCR and Western blot analysis revealed that Poly I:C and LPS pre-treatments up-regulated the expression of IL-10 and IL-6 in ADSCs, respectively. Furthermore, only Poly I:C-preconditioned ADSCs significantly promoted proliferation while inhibiting apoptosis in IL-1β-treated chondrocytes. Additionally, Poly I:C-preconditioned ADSCs downregulated MMP13 expression while upregulating aggrecan and collagen II expression levels in IL-1β-treated chondrocytes. TLR3 activation polarizes ADSCs into an immunomodulatory phenotype distinct from TLR4 activation, exerting differential effects on reversing the osteoarthritic phenotype of chondrocytes; thus indicating that MSCs' paracrine effect regulated by TLRs signaling impacts the efficacy of intra-articular MSCs injection.

Glenohumeral Osteoarthritis: A Biological Advantage or a Missed Diagnosis?

(1) Background: Osteoarthritis is a degenerative joint disease that is commonly diagnosed in the aging population. Interestingly, the lower extremity joints have a higher published incidence of osteoarthritis than the upper extremity joints. Although much is known about the disease process, it remains unclear why some joints are more affected than others. (2) Methods: A comprehensive literature review was conducted utilizing the search engines PubMed, Google Scholar, and Elsevier from 2014 to 2024, directing our search to osteoarthritis of various joints, with the focus being on glenohumeral osteoarthritis. (3) Results and Discussion: The literature review revealed a publication difference, which may be explained by the inconsistency in classification systems utilized in the diagnosis of shoulder osteoarthritis. For instance, there are six classification systems employed in the diagnosis of glenohumeral osteoarthritis, making the true incidence and, therefore, the prevalence unobtainable. Furthermore, susceptibility to osteoarthritis in various joints is complicated by factors such as joint anatomy, weight-bearing status, and prior injuries to the joint. (4) Conclusions: This review reveals the lack of understanding of shoulder osteoarthritis's true incidence and prevalence while considering the anatomy and biomechanics of the glenohumeral joint. In addition, this is the first paper to suggest a single criterion for the diagnosis of glenohumeral osteoarthritis.

Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.

Exercise-Based Interventions Are Effective in the Management of Patients with Thumb Carpometacarpal Osteoarthritis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Exercise-based interventions are a common management strategy in patients with thumb carpometacarpal joint osteoarthritis (CMCJ OA); however, their exact effect on or the use of an optimal training programme for reducing pain and disability remains unclear. Our purpose was to evaluate the effectiveness of exercise-based interventions compared with other conservative interventions in patients with CMCJ OA. We performed a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fourteen randomised clinical trials with 1280 patients were finally included. Exercise-based interventions present statistically and clinically better outcomes in reducing pain intensity (mean difference [MD]: -21.91; 95% confidence interval [CI]: -36.59, -7.24; p = 0.003) and wrist disability (MD: -8.1, 95% CI: -4.6, -11.5; p = 0.02) compared with no treatment at short-term follow-up. Proprioceptive exercises have statistically and clinically better outcomes compared with standard care only in pain intensity at very short-term (standardised mean difference [SMD]: -0.76; 95% CI: -1.30, -0.21; p = 0.007) and short-term (SMD: -0.93; 95% CI: -1.86, -0.01; p = 0.049) follow-up and statistically better results in wrist disability at very short-term (SMD: -0.94; 95% CI: -1.68, -0.21; p = 0.01) follow-up. No differences were found between the comparators at mid- and long-term follow-up. Low to moderate certainty of evidence suggests that exercise-based interventions can provide clinically better outcomes compared with no treatment in patients with thumb CMCJ OA, at least in the short term.

SUCCINATE-RECEPTOR SYSTEM OF BONE AND CARTILAGE TISSUE IN PATIENTS WITH METABOLIC PHENOTYPE OF OSTEOARTHRITIS

Introduction. Currently, osteoarthritis (OA) has been identified as a polyetiological disease, where several phenotypes have been identified based on the leading frequency. Obviously, each clinical phenotype corresponds only to its fundamental changes on the part of various organs and systems. Un-til recently, special attention was paid to the study of metabolic processes in osteoarthritis (OA) and was paid to the state of the cartilage, but more and more interest was focused on the biochemistry of the subchondral bone, its microarchitectonics and signal function. Aid. To study the features of the manifestation of the succinate-receptor system of bone and cartilage tissue in patients with the metabolic phenotype of osteoarthritis. Material and methods. 42 patients took part in the study and were divided into 2 groups: 1 group – patients without articular disease, normal body mass index; 2 group – patients with metabolic phenotype of OA. The subjects were collected complaints, anamnesis, as well as general clinical and orthopedic examination. The levels of succinate, succinate receptor (SUCNR1) and succinate dehydrogenase (SDH) are measured in bone and cartilage tissue homogenates. Results. In the 2 group, an increase in SUCNR1 expression was detected in all studied areas of the joint in comparison with the 1 group. In the 2 group, the differences were tissue-specific in the distribution of SUCNR1 with a predominant increase in the amount of the receptor in the subchondral bone compared to the loaded (p=0.031) and non-loaded zone of cartilage (p=0.001). In the 1 group, the studied areas of cartilage and bone did not dif-fer in the amount of SUCNR1 from each other. In the group of patients with the metabolic phenotype of OA, an increase in mitochondrial succinate was found both in the subchondral bone tissue and in different zones of cartilage compared to the 1 group. The final indicators of SDH activity in the mito-chondria of the studied joint zones that we obtained turned out to be low in both groups, however, relatively high enzyme activity was observed in the subchondral zone of the bone of the group of metabolic phenotype of OA. Conclusion. In patients with the metabolic phenotype of OA, high expression of SUCNR1 in joint tissues is observed, which is tissue-specific with a predominant increase in the amount of SUCNR1 in the subchondral bone. We found higher levels of succinate in the subchondral bone and cartilaginous areas of joints in patients with the metabolic phenotype of OA and suggest that the succinate-SUCNR1 interaction in affected joints in OA is adaptive in nature.

Low-Level Laser Therapy for Thumb Carpometacarpal Joint Osteoarthritis: A Randomized Controlled Trial.

Background and aim Low-level laser therapy (LLLT) is considered a promising non-invasive treatment option for osteoarthritis (OA). The current study aimed to evaluate the effectiveness of LLLT on patients with OA of the first carpometacarpal joint (CMC1) of the thumb. Methods An open-level, prospective, randomized controlled trial was conducted in the Department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, for one year. Initially, 120 patients were approached for the study. Among them, 112 eligible patients were randomly divided into two groups: the intervention group received LLLT in addition to conservative treatment, while the control group received conservative treatment alone for four weeks. Pain and functional capability (motor) improvement were assessed on a weekly follow-up basis by using various parameters such as the visual analogue scale (VAS), Ritchie articular index (tenderness scale), grip strength, key pinch strength, Dreiser functional index, and CMC1 palmer abduction. Eventually, 90 patients completed the follow-ups and were included in the analysis. Results The majority of patients diagnosed with CMC1 joint OA were in their fifties. At baseline, patients of both intervention and control groups were indifferent in terms of demography, pain intensity, motor responses, and duration of suffering. After four weeks of treatment, results indicated an overall improvement in both groups. However, the reduction of pain and increase in functional capability were not found statistically significant (p-value: ≥0.5). Conclusion LLLT with conventional treatment was not found significantly more effective enough than conventional treatment alone, but more well-designed clinical trials with larger sample sizes are needed to reach a definitive conclusion.

Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis

ObjectiveLow vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. MethodsKnee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n ​= ​9) or sham VGX (non-VGX, n ​= ​6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. ResultsAt week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p ​= ​0.055; stance time imbalance ​= ​1.6 ​± ​1.6%) and shifted foot strike locations (p ​< ​0.001; spatial symmetry ​= ​48.4 ​± ​0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 ​± ​7.70 compared to the non-VGX animal sensitivity of 29.74 ​± ​9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p ​= ​0.076; VGX: 0.80 ​± ​0.036 ​mm2; non-VGX: 0.736 ​± ​0.066 ​mm2). No group differences in systemic inflammation were observed at endpoint. ConclusionsVGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.