Progressive Joint Disease Research Articles

Optimizing knee osteoarthritis severity prediction on MRI images using deep stacking ensemble technique.

Knee osteoarthritis (KOA) represents a well-documented degenerative arthropathy prevalent among the elderly population. KOA is a persistent condition, also referred to as progressive joint Disease, stemming from the continual deterioration of cartilage. Predominantly afflicting individuals aged 45 and above, this ailment is commonly labeled as a "wear and tear" joint disorder, targeting joints such as the knee, hand, hips, and spine. Osteoarthritis symptoms typically increase gradually, contributing to the deterioration of articular cartilage. Prominent indicators encompass pain, stiffness, tenderness, swelling, and the development of bone spurs. Diagnosis typically involves the utilization of Radiographic X-ray images, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) Scan by medical professionals and experts. However, this conventional approach is time-consuming, and also sometimes tedious for medical professionals. In order to address the limitation of time and expedite the diagnostic process, deep learning algorithms have been implemented in the medical field. In the present investigation, four pre-trained models, specifically CNN, AlexNet, ResNet34 and ResNet-50, were utilized to predict the severity of KOA. Further, a Deep stack ensemble technique was employed to achieve optimal performance resulting to the accuracy of 99.71%.

A modified approach to portal placement for arthroscopic management of osteochondritis dissecans lesions of the tarsocrural joint in 15 dogs (19 tarsi).

To describe the surgical technique and outcomes of arthroscopic treatment for talar osteochondritis dissecans (OCD) in dogs, using scope and instrument portals placed on the same side of the joint as the lesion. Retrospective case series. Fifteen client-owned dogs (19 tarsi). The records of dogs with talar OCD lesions managed by arthroscopy using this modified approach to portal placement were reviewed. Signalment, owner-completed questionnaires-the Canine Brief Pain Inventory (CBPI) and a visual analog scale (VAS)-together with clinical and imaging data, surgical techniques, and postoperative complications were recorded. Mid- to long-term outcomes (over 6 months) were assessed using orthopedic examinations, osteoarthritis radiographic scores, and owner-completed questionnaires. Visualization of the affected articular structures was adequate in all cases. The multiple OCD fragments identified on CT scans were removed without intraoperative complication in 17 tarsi. Mini-arthrotomy was performed in one dog and mini-tenotomy of the deep digital flexor sheath was performed in another. Minor postoperative complications (synovial cysts) were reported in four cases. Mid- to long-term outcomes were good to excellent in 11 of the 14 dogs with substantial improvement in lameness, CBPI, and VAS scores compared with preoperative results. Degenerative joint disease progression was observed in 10 of the 14 cases. The modified arthroscopic technique resulted in few complications, rapid clinical improvement, and full or acceptable function in most cases. This modified approach to portal placement is an appealing and suitable alternative to the approach described previously for managing tarsal OCD lesions.

Macrophage Membrane-Biomimetic Multi-Layered Nanoparticles Targeting Synovial Angiogenesis for Osteoarthritis Therapy.

Osteoarthritis (OA) is an inflammatory and progressive joint disease characterized by angiogenesis-mediated sustained, chronic, and low-grade synovitis. Anti-angiogenesis is emerging as a strategy for attenuating OA progression, but is often compromised by poor targeted drug delivery and immune clearance. Recent studies have identified macrophages formed a "protective barrier" in the lining layer (LL) of synovium, which blocked the communication of joint cavity and sublining layer (SL) of synovium. Inspired by natural mimicry, macrophage membrane-camouflaged drug delivery is explored to avoid immune clearance. Based on the single cell RNA sequencing, the CD34+ synovial cells are identified as "sentinel cells" for synovium angiogenesis. Consequently, CD34 antibody-modified macrophage membraneis constructed to target new angiogenesis. Hence, a biomimetic multi-layered nanoparticle (NP) is developed that incorporates axitinib-loaded poly(lactic-co-glycolic) acid (PLGA) with CD34 antibody modified macrophage membrane (Atb@NP@Raw@CD34) to specifically deliver axitinib (Atb) to the SL and sustain inhibiting angiogenesis without immune elimination. It is found that the Atb@NP@Raw@CD34 can pass through macrophage "barrier", specifically targeting CD34+ cells, continuously releasing Atb and anti-angiogenesis in OA synovitis. Furthermore, in vivo data demonstrated that Atb@NP@Raw@CD34 can attenuate joint degeneration by inhibiting synovium angiogenesis-mediated synovitis. In conclusion, local injection of Atb@NP@Raw@CD34 presents a promising approach for clinically impeding OA progression.

Isoquercetin Ameliorates Osteoarthritis via Nrf2/NF-κB Axis: An InVitro and InVivo Study.

Osteoarthritis (OA) is a progressive joint disease characterized by extracellular matrix (ECM) degradation and inflammation, which is involved with pathological microenvironmental alterations induced by damaged chondrocytes. However, current therapies are not effective in alleviating the progression of OA. Isoquercetin is a natural flavonoid glycoside compound that has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that isoquercetin has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, through western bolt, qRT-PCR and ELISA, it was found that isoquercetin could reduce the increase of ADAMTS5, MMP13, COX-2, iNOS and IL-6 induced by IL-1β, suggesting that isoquercetin could inhibit the inflammation and ECM degradation of chondrocytes. Through nuclear-plasma separation technique, western blot and immunocytochemistry, it can be found that Nrf2 and NF-κB pathways are activated in this process, and isoquercetin may rely on this process to play its protective role. Invivo, the results of X-ray and SO staining show that intra-articular injection of isoquercetin reduces the degradation of cartilage in the mouse OA model. In conclusion, the present work suggests that isoquercetin may benefit chondrocytes by regulating the Nrf2/NF-κB signaling axis, which supports isoquercetin as a potential drug for the treatment of OA.

Pain Relief, Functional Recovery, and Chondroprotective Effects of Angelica gigas Nakai in Osteoarthritis Due to Its Anti-Inflammatory Property: An In Vitro and In Vivo Study.

Osteoarthritis (OA), characterized by chronic pain and joint degradation, is a progressive joint disease primarily induced by age-related systemic inflammation. Angelica gigas Nakai (AG), a medicinal plant widely used in East Asia, exhibits promising results for such conditions. This study aimed to evaluate the potential of AG as a drug candidate for modulating the multifaceted pathology of OA based on its anti-inflammatory properties. We evaluated the efficacy of AG in pain relief, functional improvement, and cartilage erosion delay using monosodium iodoacetate-induced OA rats and acetic acid-induced writhing mice, along with its anti-inflammatory effects on multiple targets in the serum and cartilage of in vivo models and lipopolysaccharide-stimulated RAW 264.7 cells. In vivo experiments demonstrated significant analgesic and chondroprotective effects of AG, along with functional recovery, in model animals compared with the active controls. AG dose-dependently modulated inflammatory OA pathology-related targets, including interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-13, and cyclooxygenase-2, both in vitro and in vivo. In conclusion, AG could be a potential drug candidate for modulating the multifaceted pathology of OA. Nevertheless, further comprehensive investigations, involving a broader range of compounds, pathologies, and mechanisms, are warranted to validate these findings.

Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

A Preliminary Protocol of Radiographic Image Processing for Quantifying the Severity of Equine Osteoarthritis in the Field: A Model of Bone Spavin

Osteoarthritis (OA) of the tarsal joint, also known as bone spavin, is a progressive joint disease that increases in severity with age. It is a significant cause of hind limb lameness, leading to a deterioration in the quality of life of horses, particularly in old age. In this study, the tarsal joints of 20 older horses aged 15 to 35 years were radiographically imaged and processed using the computed digital absorptiometry (CDA) method for bone mineral density (BMD) assessment. The radiological signs of bone spavin were scored on a scale ranging from normal (0) to severe OA (3), and the examined joints were grouped according to the severity of OA. The percentage of color pixels (%color pixels), representing successive steps on the scale of X-ray absorption by a density standard, differed between the steps in a BMD characteristic manner for each group. Furthermore, two examined ranges of relative density allowed for the distinction of joints affected by severe OA from other joints, while another two ranges allowed for the differentiation of joints affected by moderate and severe OA from normal joints. The proposed color annotation-assisted decomposition of radiological images based on the CDA protocol shows promise for advancing research on the quantification of radiological signs of OA. This approach could be valuable for monitoring the progression of the disease in older horses.

Time-Dependent Effect of Eggshell Membrane on Monosodium-Iodoacetate-Induced Osteoarthritis: Early-Stage Inflammation Control and Late-Stage Cartilage Protection.

Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet®, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet®, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.

Cumulative loading increases and loading asymmetries persist during walking for people with a transfemoral bone-anchored limb

BackgroundA bone-anchored limb (BAL) is an alternative to a traditional socket-type prosthesis for people with transfemoral amputation. Early laboratory-based evidence suggests improvement in joint and limb loading mechanics during walking with a BAL compared to socket prosthesis use. However, changes in cumulative joint and limb loading measures, which may be predictive of degenerative joint disease progression, remain unknown. Research questionDo cumulative total limb and hip joint loading during walking change using a BAL for people with unilateral transfemoral amputation, compared to prior socket prosthesis use? MethodsA case-series cohort of eight participants with prior unilateral transfemoral amputation who underwent BAL hardware implantation surgery were retrospectively analyzed (4 M/4 F; BMI: 27.7 ± 3.1 kg/m2; age: 50.4 ± 10.2 years). Daily step count and whole-body motion capture data were collected before (using socket prosthesis) and one-year after BAL hardware implantation. Cumulative total limb and hip joint loading and between-limb loading symmetry metrics were calculated during overground walking at both time points and compared using Cohen’s d effect sizes. ResultsOne year after BAL hardware implantation, participants demonstrated bilateral increases in cumulative total limb loading (amputated: d = -0.65; intact: d = -0.72) and frontal-plane hip moment (amputated: d = -1.29; intact: d = -1.68). Total limb loading and hip joint loading in all planes remained asymmetric over time, with relative overloading of the intact limb in all variables of interest at the one-year point. SignificanceDespite increases in cumulative total limb and hip joint loading, between-limb loading asymmetries persist. Habitual loading asymmetry has been implicated in contributing to negative long-term joint health and onset or progression of degenerative joint diseases. Improved understanding of methods to address habitual loading asymmetries is needed to optimize rehabilitation and long-term joint health as people with transfemoral amputation increase physical activity when using a BAL.

Arctiin Protects Chondrocytes From Interleukin-1β-Induced Inflammation and Apoptosis by RNA Sequence In vivo and In vitro

Abstract Objective: Osteoarthritis (OA) is a progressive joint disease characterized by degeneration and destruction of articular cartilage. Arctiin (ARC) has been shown in many studies to have potential anti-inflammatory, anti-apoptotic, and antioxidant effects in various diseases. However, the mechanism by which ARC exerts its protective effects in OA is not fully understood. Here, we explore the mechanism by which ARC plays its protective role in OA. Materials and Methods: Mouse chondrocytes were isolated and characterized through toluidine blue staining and collagen II immunofluorescence labeling. A mouse-based experimental model was developed to induce chondrocyte inflammation through Interleukin-1β (IL-1β). Subsequently, ARC was administered in various doses to mitigate this inflammation. Techniques such as biochemical assays, Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence labeling were employed to detect changes in nitric oxide (NO), lactate dehydrogenase (LDH), inflammatory markers, and components of the cartilage matrix in chondrocytes. RNA-sequencing (RNA-seq) was utilized to explore variations in gene expression among chondrocytes across different groups. The genes and signaling pathways that were identified underwent analysis through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment studies. Validation of gene and protein expression was carried out using qRT-PCR, Western blotting, and cellular flow cytometry, based on the results from sequencing. Furthermore, Safranin-O fast green staining and immunohistochemistry staining were performed on slices of the mice knee joint to evaluate the OA Research Society International score, alterations in the cartilage matrix, and levels of apoptosis-related proteins at sites of knee cartilage damage in an arthritis model induced by monosodium iodoacetate (MIA) and physical activity. Results: It was found that ARC effectively inhibits the production of IL-1β-induced chondrocytes’ inducible NO synthase, cyclooxygenase-2, NO, LDH, IL-6, and tumor necrosis factor-α. ARC exhibited a dose-dependent effect on chondrocytes by reducing IL-1β-induced matrix metalloproteinase-3 (MMP-3) and a disintegrin and metalloproteinase with thrombospondin motifs-5 levels while increasing Aggrecan levels. RNA-seq and bioinformatics analysis revealed that ARC’s therapeutic effects involve apoptotic signaling pathways through the downregulation of Bcl-2-associated X protein (Bax) and caspase-3 expression and the upregulation of B-cell lymphoma-2 (Bcl-2) expression in IL-1β-induced chondrocytes. ARC significantly raised the levels of aggrecan and Bcl-2 and decreased the levels of MMP-3, Bax, and caspase-3 in an arthritis model induced by MIA and movement. Conclusions: Through RNA-seq, in vitro cell assays, and in vivo experiments, this research established the link between apoptosis and inflammation in the progression of OA and confirmed the protective effects of ARC on chondrocytes and its key targets. This highlights ARC’s therapeutic potential and its role in the development of treatments for OA.

Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Changes in analgesic prescribing among older adults hospitalised for osteoarthritis or joint replacements

Abstract Introduction Osteoarthritis is a chronic, progressive joint disease, associated with frequent pain, and functional decline. The primary risk factor for developing osteoarthritis is advanced age. Older patients are more susceptible to the adverse effects of commonly prescribed analgesics such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs), owing to a greater prevalence of comorbidities and age-related changes in this cohort. The analgesic burden and prescribing trends in this cohort are largely unknown in the Irish context despite their increased susceptibility to adverse effects. Aim This study aims to evaluate analgesic prescribing patterns before and after an osteoarthritis or joint arthroplasty related hospital admission in patients aged ≥65 years and to identify factors associated with long-term prescribing of opioids and oral NSAIDs post-discharge. Methods This was an observational study of older adults with an osteoarthritis or joint arthroplasty hospitalisation. Data were collected for a larger study from 44 general practices in Ireland from 2012-2018 and included general practice records (12 months pre/post-index hospitalisation) and hospital discharge summaries, which was extracted as anonymous data from the practice software system. The analysis described prevalence of use of analgesics in the 12 months pre and post their hospitalisation. To assess long-term prescribing, multivariable analysis assessed discharge prescription and patient characteristics associated with opioid and oral NSAID use 3-12 months post-discharge. Results Overall, 738 individuals were included (52.9% female, mean age 78.1 years). Compared to 12 months pre-hospitalisation, patients were less likely to be prescribed a weak opioid or oral NSAID from discharge to 3 months post-discharge, or in the 3-12 months post-discharge. For strong opioids, prescribing was significantly less likely in the 3-12 months post-discharge compared to pre-discharge (odds ratio (OR) 0.54, 95%CI 0.40-0.74). Female sex (OR 1.61, 95%CI 1.10-2.36), strong opioid prescribing at discharge (OR 2.47, 95%CI 1.56-3.90) and pregabalin discharge prescribing (OR 2.21, 95%CI 1.12-4.33) were significantly associated with long-term strong opioid prescribing 3-12 months post-discharge. For oral NSAID prescribing, lower age (OR 0.97, 95%CI 0.95-1.00), female sex (OR 1.56, 95%CI 1.08-2.25), and discharge prescribing of strong opioids (OR 1.94, 95%CI 1.23-3.04) were significantly associated. Conclusion The use of opioids and oral NSAIDs is typically reduced for patients post-discharge from an osteoarthritis or joint arthroplasty hospitalisation. Female sex and strong opioids at discharge are associated with the prescribing of strong opioids and oral NSAIDs. Although our study was limited by use of prescription records which may not accurately represent what was dispensed or utilised by patients, it is the first to examine changing patterns of analgesic prescribing among osteoarthritis/joint arthroplasty patients. This contributes knowledge on modifiable characteristics which could reduce long-term use of these medications where appropriate.

OA13 Alkaptonuria: a big mimic

Abstract Background/Aims Alkaptonuria is a rare metabolic disorder, often misdiagnosed as spondyloarthritis or degenerative musculoskeletal disease. The population most affected are young males in their 30s with characteristic arthritis involving the spine and large joints. The patient may notice their urine turning dark on standing and pigmentation over the skin and connective tissues (ochronosis); however, these subtle features may sometimes go unnoticed. Methods A 38-year-old-male with long standing back pain presented with right knee swelling. With a diagnosis of spondyloarthritis, he was previously treated with DMARDS but did not have any relief. There was a history of urine turning dark on standing. On examination, there was subtle hyperpigmentation over left ear concha and a spot on the sclera. An x-ray of the thoracic spine showed flattening and calcification of intervertebral disc spaces at multiple levels. Aspiration of synovial fluid showed suspended fragments of articular cartilage. His inflammatory markers were negative. We performed gas chromatography mass spectrometry which showed elevated excretion of homogentisic acid (HGA). A homozygous pathogenic variant in the homogentisate 1,2-dioxygenase gene associated with alkaptonuria was reported on whole genome sequencing. Results Ochronotic arthropathy is defined as progressive degenerative joint disease mainly affecting the spine and large joints. Most patients require at least one joint replacement by age 55. Small joints of hands and feet and sacroiliac joints are usually spared. Arthroscopy of the joint may reveal dark brown to black pigmented cartilage defects. The synovium may show fragments of pigmented cartilage suspended in the fluid (ground pepper sign). Plain spine radiographs may show flattening and calcifications of the intervertebral discs with a characteristic vacuum phenomenon (radiolucent gas collection). Periarticular structures like tendons and ligaments are also affected, leading to rupture in around 20-30% of patients. Alkaptonuria is also associated with decreased bone mineral density and subsequent risk for fragility fracture. Conclusion Alkaptonuria often mimics ankylosing spondylitis. A triad of ochronosis, dark urine and ochronotic arthropathy is the key to diagnosis. Definitive diagnosis is through biochemical or genetic testing. Nitisinone has proved to be effective but shows significant side effects. Management mainly involves physiotherapy and palliative care. Disclosure M. Shah: None. S. Upadhyaya: None.

The Genetic Markers of Knee Osteoarthritis in Women from Russia.

Osteoarthritis is a chronic progressive joint disease that clinically debuts at the stage of pronounced morphologic changes, which makes treatment difficult. In this regard, an important task is the study of genetic markers of the disease, which have not been definitively established, due to the clinical and ethnic heterogeneity of the studied populations. To find the genetic markers for the development of knee osteoarthritis (OA) in women from the Volga-Ural region of Russia, we conducted research in two stages using different genotyping methods, such as the restriction fragment length polymorphism (RFLP) measurement, TaqMan technology and competitive allele-specific PCR-KASPTM. In the first stage, we studied polymorphic variants of candidate genes (ACAN, ADAMTS5, CHST11, SOX9, COL1A1) for OA development. The association of the *27 allele of the VNTR locus of the ACAN gene was identified (OR = 1.6). In the second stage, we replicated the GWAS results (ASTN2, ALDH1A2, DVWA, CHST11, GNL3, NCOA3, FILIP/SENP1, MCF2L, GLT8D, DOT1L) for knee OA studies. The association of the *T allele of the rs7639618 locus of the DVWA gene was detected (OR = 1.54). Thus, the VNTR locus of ACAN and the rs7639618 locus of DVWA are risk factors for knee OA in women from the Volga-Ural region of Russia.

A Systemic Review on Nutraceutical Supplements used in the Management of Osteoarthritis.

Osteoarthritis (OA) is a progressive degenerative joint disease. It basically impairs the structural integrity of articulate cartilage and imbalances the catabolic and anabolic signals in the joint. A degenerative disease is characterized by swelling, pain, and joint stiffness. The treatment and management of osteoarthritis are based on analgesic and anti-inflammatory agents, whereas the exact cause of OA is not known yet. The negative effects of synthetic medications have led to a daily rise in the usage of nutraceuticals and dietary supplements. Clinicians are aware of these treatments, and they also recommend nutraceuticals in addition to the currently preferred therapy. Many in-vitro and in-vivo experiments have been performed in past years to evaluate the function of these on osteoarthritis. The collection of articles was published on search engines like PubMed, Scopus, Google Scholar, ResearchGate, and ScienceDirect. The evaluation covers every potential nutraceutical utilized in osteoarthritis, together with its supporting data and mode of action. The present review discusses nutraceuticals, including devil's claw, vitamin D, boswellic acid, capsaicin, ginger, curcumin, krill oil, ginger, and avocado/soybean unsaponifiable.

5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8–11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.

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

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

Investigating the effect of an Orem-based self-care educative supportive nursing system on the joint function of patients with knee osteoarthritis.

Osteoarthritis is the most common form of arthritis. It is a common progressive joint disease characterized by chronic pain and functional disability, which disturbs functional movements, body balance, and quality of life in patients with knee osteoarthritis. This study investigates the effect of an Orem-based self-care educative supportive nursing system on the joint function of patients with knee osteoarthritis. This semi-experimental paper studies 130 patients with knee osteoarthritis. The patients are selected using convenience sampling and randomly assigned to intervention and control groups equally. The K00S questionnaire was used to collect patients' demographic information and other information relating to their knees' function. We carried out interventions for six weeks, with a session of 45 to 60 minutes each week. Data were collected before the intervention and three months after the intervention. SPSS 21.0 and descriptive and inferential statistics were used to analyze the collected data at the significance level of 0.05. The results show significant differences between the two groups in terms of joint symptoms (P = 0.001), pain (P = 0.001), daily activities (P = 0.001), sports and recreational activities (P = 0.001), and quality of life (P = 0.02). In other words, there was a significant difference in the average subscale scores of activities in all five dimensions between the intervention and control groups (P < 0.05). Orem's self-care model has a positive and significant effect on the functional movement of patients with knee osteoarthritis and improves their joint function.

What is the association of depression with clinical response to therapy in patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs?

Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002). Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity.

Normal joint range of motion in children with Down syndrome.

Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective of this study was to establish normative joint ROM values, using a standardized measurement approach, for upper and lower joints of healthy children of both genders with DS. This study evaluated joint ROM in healthy males and females with DS who had no previous musculoskeletal pathology. Younger males have more ROM than females at the same age and both genders lose ROM with age but continue to have increased ROM in the ankles compared to children without DS. This study establishes optimal estimates of joint ROM in children with DS, and this information should be helpful to clinicians when assessment requires evaluation of joint ROM to know if evaluation falls within the normal ROM. This reference should be helpful to track joint disease progression over time or as part of a musculoskeletal screen for abnormal joint ROM in children with DS.