Features Of Osteoarthritis Research Articles

PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action.

Osteoarthritis (OA) is one of the most common degenerative joint diseases, often involving the entire joint. The degeneration of articular cartilage is an important feature of OA, and there is growing evidence that the mitochondrial biogenesis master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) exert a chondroprotective effect. PGC-1α delays the development and progression of OA by affecting mitochondrial biogenesis, oxidative stress, mitophagy and mitochondrial DNA (mtDNA) replication in chondrocytes. In addition, PGC-1α can regulate the metabolic abnormalities of OA chondrocytes and inhibit chondrocyte apoptosis. In this paper, we review the regulatory mechanisms of PGC-1α and its effects on OA chondrocytes, and introduce potential drugs and novel nanohybrid for the treatment of OA which act by affecting the activity of PGC-1α. This information will help to further elucidate the pathogenesis of OA and provide new ideas for the development of therapeutic strategies for OA.

Hippo/YAP1 inhibition by verteporfin attenuates osteophyte formation in a mouse surgical osteoarthritis model

Osteophyte is an outgrowth of cartilage formed at the margins of the affected joint through endochondral ossification-like processes, and is one of the most common radiographic features of osteoarthritis (OA) that has been used to define the stage of disease. Osteophyte has been regarded to adapt the joint to the altered biomechanics of OA patients, limits joint movement and represent a source of joint pain, however, the mechanism of osteophyte formation, the morphology characteristics and biomechanical properties of osteophyte cells are remained unclear. In the present study, we isolated osteophyte cells and chondrocytes from late-stage OA patients who underwent total knee replacement surgeries, by applying Atomic Force Microscopy (AFM), we identified osteophyte cells were in irregular shape with dendrites, shrunk cell body, smooth surface and high elastic modulus (23.3 ± 5.4 kPa) when compared with chondrocytes (6.5 ± 1.8 kPa). In addition, osteophyte cells showed higher proliferation ability and colony formation capacity than chondrocytes. Mechanistically, we identified YAP1, the core transcriptional factor of Hippo signaling pathway, was highly expressed in osteophyte cell both at protein and RNA levels. Inactivation of Hippo/YAP1 signaling pathway by Verteporfin is sufficient to inhibit osteophyte cell proliferation in vitro and attenuate osteophyte formation in vivo. In conclusion, the morphology characteristic and biomechanical property of osteophyte cells at single cell level are quite different from chondrocytes, although we could not exclude other regulatory mechanisms, our findings suggested that Hippo/YAP1 is of great importance for osteophyte formation.

The computed tomography characteristics of lumbar facet joints in spondylosis patients

Objective: To demonstrate the computed tomography (CT) features of lumbar facet joints in spondylosis patients. Subject and method: It was a cross-sectional and descriptive study including 42 spondylosis patients (416 lumbar facet joints) who took consultation in 108 Military Central Hospital, from December 2021 to July 2022. The subjects were recruited as the correspondence between Gomez Vega 2019 clinical criteria and CT scan. The examined index included: Joint shapes which were C-shaped, straight shape, J-shaped; joint angles regarding sagittal line; joint tropisms. Osteoarthritis characteristics of lumbar facet joints based on Pathria classification with 4 grades. Data were analyzed by SPSS, comparisons of two means were performed by T-test. Statistical significance was defined by p<0.05. Result: Average age of patients was 63.79 ± 2.24 years old, female/male ratio was 4.25. 2/42 (4.76%) patients had sacralization of L5. The proportions of joint shapes (C, straight and J) were 86.76%, 13.24%, 0% respectively. The angle of joints increased in respect of descending levels, from 31.14 ± 8.78o (L12) to 45.61 ± 11.20o (L5S1). The average of articular tropisms in each level were ranged from 5.47 ± 4.09o to 7.58 ± 7.22o. The percentages of Pathria classification (grade 0, 1, 2, 3) were 2.40%, 59.62%, 11.06%, 26.92%, respectively. Pathria 3 dominantly distributed at L45 level (Left 47.62% and right 42.86%). Subchondral sclerosis and hypertrophy contributed to the highest rate of degenerative characteristics (99.03% and 92.51% respectively). Conclusion: C-shaped joint was the most popular. Large tropism might be a consequence of prolonged osteoarthritis. Subchondral sclerosis and hypertrophy presented at almost facet joints. Pathria grade 3 was the most popular at L45 level which had higher percentage of severe osteoarthritis features.

Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling.

Objective: Synovitis and fibrosis are common pathological features of knee osteoarthritis (KOA). The interaction of synovitis and fibrosis can promote KOA progression. Chrysin (CHR), a natural flavonoid, may treat inflammation and prevent fibrosis. However, the effect and mechanism of CHR in KOA synovitis and fibrosis remains unclear. Methods: The KOA model was established in male SD rats by anterior cruciate ligament transection (ACLT), and histological analysis was used to evaluate synovitis and fibrosis. IL-6, IL-1β and TNF-α mRNA expression in synovial tissue was measured by qRT‒PCR. Immunohistochemistry (IHC) was performed to detect GRP78, ATF-6 and TXNIP expression in vivo. Synovial fibroblasts (SFs) were treated with TGF-β1 to stimulate the inflammatory response and fibrosis. CCK-8 assays were used to detect the viability of CHR-treated SFs. The IL-1β level was detected by immunofluorescence analysis. Coimmunoprecipitation (Co-IP) and double immunofluorescence colocalization were used to detect the physiological interaction between TXNIP and NLRP3. The expression of fibrosis-related mediators and PERK/TXNIP/NLRP3 signaling molecules was detected by western blotting and qRT-PCR. Results: Four weeks after CHR treatment, pathological sections and associated scores showed that CHR improved synovitis and fibrosis in the ACLT model. In vitro, CHR attenuated the TGF-β1-induced inflammatory response and fibrosis in SFs. Moreover, CHR suppressed the expression of synovial fibrosis markers and PERK/TXNIP/NLRP3 signaling molecules in the synovial tissue of rats with ACLT and cultured SFs. More importantly, we found that CHR inhibited TXNIP-NLRP3 interactions in TGF-β-induced SFs. Conclusion: Our findings indicate that CHR can ameliorate synovitis and fibrosis in KOA. The underlying mechanism may be related to the PERK/TXNIP/NLRP3 signaling pathway.

Evaluation Of Osteoarthritic Features In Peripheral Joints By Ultrasound Imaging: A Systematic Review

Evaluation Of Osteoarthritic Features In Peripheral Joints By Ultrasound Imaging: A Systematic Review

Comparison of Digital Radiography, Computed Tomography, and Magnetic Resonance Imaging Features in Canine Spontaneous Degenerative Stifle Joint Osteoarthritis

Canine stifle joint osteoarthritis (OA) is characterized by damage and degeneration of the articular cartilage and subchondral bone, bony hypertrophy at the margins, and synovial joint membrane changes. Non-invasive imaging modalities, such as digital radiography (DR), computed tomography (CT), and magnetic resonance imaging (MRI), can be used to describe these changes. However, the value of MRI in diagnosing spontaneous canine OA and the comparison of different imaging modalities have seldom been addressed. This study compared multiple noninvasive imaging modalities in canine spontaneous stifle OA cases. Four client-owned dogs with five spontaneously affected OA stifle joints were recruited and underwent DR, CT, and MRI. Information on osteophytes/enthesophytes, ligament/tendon lesions, synovial effusion and membrane thickening, subchondral bone lesions, and meniscal and cartilage lesions were scored and compared. The results showed that MRI provides the most comprehensive and superior lesion detection sensitivity for ligament, meniscus, cartilage, and synovial effusions. DR provides adequate bony structure information, while CT provides the most delicate images of bony structure lesions. These imaging findings may provide further understanding of the disease and help clinicians draft a more precise treatment plan.

Metabolic syndrome and the progression of knee osteoarthritis on MRI

Metabolic osteoarthritis (OA) is one of the proposed clinical phenotypes defined by the existence of metabolic syndrome (MetS). This study aimed to (1) investigate whether MetS and its components are associated with progression of knee OA magnetic resonance imaging (MRI) features, and (2) to evaluate the interaction of MetS with menopause and progression of MRI features. 682 women from the Rotterdam Study who participated in a sub-study with knee MRI data available and 5-year follow-up were included. Tibiofemoral (TF) and patellofemoral (PF) OA features were assessed with the MRI Osteoarthritis Knee Score. MetS was quantified by the MetS severity Z-score. Generalized estimating equations were used to evaluate associations between MetS and menopausal transition and progression of MRI features. MetS severity at baseline was associated with progression of osteophytes in all compartments, bone marrow lesions (BMLs) in the PF compartment, and cartilage defects in the medial TF compartment. Waist circumference was associated with progression of osteophytes in all compartments and cartilage defects in the medial TF compartment. High-density lipoprotein (HDL)-cholesterol levels were associated with progression of osteophytes in the medial and lateral TF compartment and glucose levels with osteophytes in the PF and medial TF compartment. No interactions were found between MetS with menopausal transition and MRI features. Women with higher MetS severity at baseline showed progression of osteophytes, BMLs, and cartilage defects, indicating more structural knee OA progression after 5 years. Further studies are required to understand whether targeting MetS components may prevent the progression of structural knee OA in women.

Deep learning applications in osteoarthritis imaging.

Deep learning (DL) is one of the most exciting new areas in medical imaging. This article will provide a review of current applications of DL in osteoarthritis (OA) imaging, including methods used for cartilage lesion detection, OA diagnosis, cartilage segmentation, and OA risk assessment. DL techniques have been shown to have similar diagnostic performance as human readers for detecting and grading cartilage lesions within the knee on MRI. A variety of DL methods have been developed for detecting and grading the severity of knee OA and various features of knee OA on X-rays using standardized classification systems with diagnostic performance similar to human readers. Multiple DL approaches have been described for fully automated segmentation of cartilage and other knee tissues and have achieved higher segmentation accuracy than currently used methods with substantial reductions in segmentation times. Various DL models analyzing baseline X-rays and MRI have been developed for OA risk assessment. These models have shown high diagnostic performance for predicting a wide variety of OA outcomes, including the incidence and progression of radiographic knee OA, the presence and progression of knee pain, and future total knee replacement. The preliminary results of DL applications in OA imaging have been encouraging. However, many DL techniques require further technical refinement to maximize diagnostic performance. Furthermore, the generalizability of DL approaches needs to be further investigated in prospective studies using large image datasets acquired at different institutions with different imaging hardware before they can be implemented in clinical practice and research studies.

Changes and Associations Between Gait Biomechanics and Knee Inflammation After Aspiration and Glucocorticoid Injection for Knee Osteoarthritis.

Although knee inflammation is thought to adversely affect joint function in patients with knee osteoarthritis (OA), the effects of reducing knee inflammation on gait biomechanics and strength are unknown. Our objectives were to compare ultrasound (US) measures of knee inflammation, gait biomechanics, knee extension and flexion strength, and pain before and after knee aspiration and glucocorticoid injection, and to explore associations among changes. Forty-nine patients (69 knees) with symptomatic knee OA and synovitis were tested before and 3-4 weeks after US-guided knee aspiration and glucocorticoid injection. At each visit, participants completed US assessments for inflammatory features of knee OA, 3D gait analysis, isokinetic knee extension and flexion strength tests, and Knee Osteoarthritis Outcome Score (KOOS) pain subscales. Linear and polynomial mixed-effects regression models were used to investigate changes and their associations. Changes were observed for the synovitis score (unstandardized β [post-injection minus pre-injection] -0.55/9 [95% confidence interval (95% CI) -0.97, -0.12]), effusion depth (-1.05 mm [95% CI -1.07, -0.39]), KOOS pain (unstandardized β 5.91/100 [95% CI 1.86, 9.97]), peak external knee flexion and extension moments (KFM; 3.33 Nm [95% CI 0.45, 6.22]), KEM (-2.99 Nm [95% CI -5.93, -0.05]), and knee extension strength (4.70 Nm [95% CI 0.39, 9.00]) and flexion strength (3.91 Nm [95% CI 1.50, 6.81]). The external KFM increased during 13-38% and 76-89% of stance post-injection. When controlled for time, greater synovitis was associated with lower knee extension strength, while lower pain was associated with increased knee extension and flexion strength. In patients with knee OA and synovitis, reduced inflammation and pain after aspiration and glucocorticoid injection are associated with changes in knee gait biomechanics and strength.

Sustained-release losartan from peptide nanofibers promotes chondrogenesis.

Introduction: The central pathologic feature of osteoarthritis (OA) is the progressive loss of articular cartilage, which has a limited regenerative capacity. The TGF-β1 inhibitor, losartan, can improve cartilage repair by promoting hyaline rather that fibrous cartilage tissue regeneration. However, there are concerns about side effects associated with oral administration and short retention within the joint following intra-articular injections. To facilitate local and sustained intra-articular losartan delivery we have designed an injectable peptide amphiphile (PA) nanofiber that binds losartan. The aims of this study are to characterize the release kinetics of losartan from two different PA nanofiber compositions followed by testing pro-regenerative bioactivity on chondrocytes. Methods: We tested the impact of electrostatic interactions on nanostructure morphology and release kinetics of the negatively charged losartan molecule from either a positively or negatively charged PA nanofiber. Subsequently, cytotoxicity and bioactivity were evaluated in vitro in both normal and an IL-1β-induced OA chondrocyte model using ATDC5. Results: Both nanofiber systems promoted cell proliferation but that the positively-charged nanofibers also significantly increased glycosaminoglycans production. Furthermore, gene expression analysis suggested that losartan-encapsulated nanofibers had significant anti-inflammatory, anti-degenerative, and cartilage regenerative effects by significantly blocking TGF-β1 in this in vitro system. Discussion: The results of this study demonstrated that positively charged losartan sustained-release nanofibers may be a novel and useful treatment for cartilage regeneration and OA by blocking TGF-β1.

Association of Traumatic Knee Injury With Radiographic Evidence of Knee Osteoarthritis in Military Officers.

The association between knee injury and knee osteoarthritis (OA) is understudied relative to its importance, particularly in younger populations. This study was undertaken to examine the association of knee injury with radiographic features of knee OA in military officers, who have a physically demanding profession and high rates of knee injury. Participants were recruited in 2015-2017 from an existing program that enrolled 6,452 military officers during 2004-2009. Officers with a history of knee ligament or meniscal injuries (n=117 via medical record review) were compared to officers with no history of knee injury (n=143). Bilateral posteroanterior knee radiographs were obtained using a standardized fixed-flexion positioning frame. All images were read for Kellgren/Lawrence (K/L) grade, osteophyte (OST), and joint space narrowing (JSN) scores. Data were analyzed using linear-risk regression models with generalized estimating equations. Injured and noninjured participants were similar (mean age 28 years, mean body mass index 25 kg/m2 , ~40% female). The mean time from first knee injury to imaging among injured participants was 9.2 years. Compared with noninjured knees, greater prevalence of radiographic OA (K/L grade ≥ 2), OST (grade ≥ 1), and JSN (grade ≥ 1) was observed among injured knees, with prevalence differences of +16% (95% confidence interval [95% CI] 10%, 22%), +29% (95% CI 20%, 38%), and + 17% (95% CI 10%, 24%), respectively. Approximately 1 in 6 officers with prior knee injury progressed to radiographic OA by age 30 years. At the midpoint of a projected 20-year military career, officers with a history of traumatic knee injury have a markedly increased prevalence of knee radiographic OA compared to officers without injury.

International multispecialty consensus on how to image, define, and grade ultrasound imaging features of first metatarsophalangeal joint osteoarthritis, a Delphi consensus study

ObjectiveTo reach consensus concerning which ultrasound imaging features should be assessed and graded, and what ultrasound imaging procedure should be performed when examining osteoarthritic change in the first metatarsophalangeal joint. DesignAn online Delphi study was conducted over four iterative rounds with 16 expert health professionals. Items were scored from 0 to 100 (0 ​= ​not at all important; 100 ​= ​extremely important). Consensus was defined based upon an item receiving a median score of ≥70% acceptance. Items receiving median score of ≤50% were rejected. Items considered ambiguous (median score 51%–69% of acceptance) were assessed in an additional round. A final round determined the content validity of items through calculation of the content validity ratio and content validity index. ResultsSixteen items were deemed essential, which included osteophytes graded dichotomously, cartilage damage graded continuously, synovitis and joint space narrowing graded on a semiquantitative scale. The panel deemed essential that the first metatarsophalangeal joint start in a neutral position, then move through range of motion for both dorsal and plantar scanning, orientating the probe in longitudinal and in transverse, whilst using first metatarsal head and proximal phalanx as anatomical landmarks. A supine body position was only deemed essential for a dorsal scan and a neutral foot/ankle position was only rated essential for a plantar scan. The content validity index of the 16 essential items was 0.19. ConclusionThe consensus exercise has identified the essential components the ultrasound imaging acquisition procedure should encompass when examining first metatarsophalangeal joint osteoarthritis.

Clinical application of ultrashort echo time (UTE) and zero echo time (ZTE) magnetic resonance (MR) imaging in the evaluation of osteoarthritis.

Novel compositional magnetic resonance (MR) imaging techniques have allowed for both the qualitative and quantitative assessments of tissue changes in osteoarthritis, many of which are difficult to characterize on conventional MR imaging. Ultrashort echo time (UTE) and zero echo time (ZTE) MR imaging have not been broadly implemented clinically but have several applications that leverage contrast mechanisms for morphologic evaluation of bone and soft tissue, as well as biochemical assessment in various stages of osteoarthritis progression. Many of the musculoskeletal tissues implicated in the initiation and progression of osteoarthritis are short T2 in nature, appearing dark as signal has already decayed to its minimum when image sampling starts. UTE and ZTE MR imaging allow for the qualitative and quantitative assessments of these short T2 tissues (bone, tendon, calcified cartilage, meniscus, and ligament) with both structural and functional reference standards described in the literature [1-3]. This review will describe applications of UTE and ZTE MR imaging in musculoskeletal tissues focusing on its role in knee osteoarthritis. While the review will address tissue-specific applications of these sequences, it is understood that osteoarthritis is a whole joint process with involvement and interdependence of all tissues. KEY POINTS: • UTE MR imaging allows for the qualitative and quantitative evaluation of short T2 tissues (bone, calcified cartilage, and meniscus), enabling identification of both early degenerative changes and subclinical injuries that may predispose to osteoarthritis. • ZTE MR imaging allows for the detection of signal from bone, which has some of the shortest T2 values, and generates tissue contrast similar to CT, potentially obviating the need for CT in the assessment of osseous features of osteoarthritis.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging Findings of Infrapatellar Fat Pad Signal Abnormalities: Comparison Between Symptomatic and Asymptomatic Knee Osteoarthritis

Infrapatellar fat pad (IPFP) proton density-weighted images (PdWI) hyperintense regions on MRI are an important imaging feature of knee osteoarthritis (KOA) and are thought to represent inflammation which may induce knee pain. The aim of the study was to compare the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) findings of PdWI hyperintense regions of IPFP between symptomatic and asymptomatic KOA and to determine whether IVIM-DWI parameters can be used as an objective biomarker for symptomatic KOA. In total, 84 patients with symptomatic KOA, 43 asymptomatic KOA persons, and 30 healthy controls with MRI were retrospectively reviewed. Demographic, IPFP-synovitis, Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain sub-score, IPFP volume and depth and quantitative parameters of IVIM-DWI were collected. The chi-square test, Binary logistic regression and receiver operating characteristic curve (ROC) analysis were used for diagnostic performance comparison. The IPFP volume and depth were statistically significant differences between the non-KOA and sKOA groups (p<0.05). The IPFP PdWI hyperintense regions demonstrated significantly higher values of D and D* in the symptomatic KOA compared to those in the asymptomatic KOA (1.51±0.47 vs. 1.73±0.40 for D and 19.24±6.44 vs. 27.09±9.75 for D*) (both p<0.05). Multivariate logistic regression analyses showed that Higher D and D* values of IPFP hyperintense region were significantly associated with higher risks of knee pain (OR: 1.97; 95% CI: 1.21-3.19; p=0.006 for D and OR: 1.24; 95% CI: 1.09-1.41; p=0.001 for D*). Sensitivity and specificity of D value for symptomatic KOA were 80.28% and 83.33%, with an AUC of 0.78 (0.68-0.86). D* value had the sensitivity with 92.96% and a specificity of 58.33%, with an AUC of 0.82 (0.73-0.89) for symptomatic KOA. IVIM-DWI can be used as an additional functional imaging technique to study IPFP with signal abnormalities on PdWI, and the D and D* values may have potential value to predict the symptom in mild-to-moderate KOA patients.

Detection Algorithm of Knee Osteoarthritis Based on Magnetic Resonance Images

Knee osteoarthritis (OA) is a common disease that impairs knee function and causes pain. Currently, studies on the detection of knee OA mainly focus on X-ray images, but X-ray images are insensitive to the changes in knee OA in the early stage. Since magnetic resonance (MR) imaging can observe the early features of knee OA, the knee OA detection algorithm based on MR image is innovatively proposed to judge whether knee OA is suffered. Firstly, the knee MR images are preprocessed before training, including a region of interest clipping, slice selection, and data augmentation. Then the data set was divided by patient-level and the knee OA was classified by the deep transfer learning method based on the DenseNet201 model. The method divides the training process into two stages. The first stage freezes all the base layers and only trains the weights of the embedding neural networks. The second stage unfreezes part of the base layers and trains the unfrozen base layers and the weights of the embedding neural network. In this step, we design a block-by-block fine-tuning strategy for training based on the dense blocks, which improves detection accuracy. We have conducted training experiments with different depth modules, and the experimental results show that gradually adding more dense blocks in the fine-tuning can make the model obtain better detection performance than only training the embedded neural network layer. We achieve an accuracy of 0.921, a sensitivity of 0.960, a precision of 0.885, a specificity of 0.891, an F1-Score of 0.912, and an MCC of 0.836. The comparative experimental results on the OAI-ZIB dataset show that the proposed method outperforms the other detection methods with the accuracy of 92.1%.

Iron accumulation in ferroptosis and the role of lipid peroxidation in osteoarthritis

Ferroptosis is a recently discovered mode of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides, which can reach lethal levels, but this process was found to be inhibited by ferroptosis inhibitor-specific reverse. Osteoarthritis (OA) is the most common degenerative joint disease characterized by complex pathogenesis including mechanical overload, elevated levels of inflammatory mediators, metabolic alterations, and cellular senescence and death. Since iron accumulation and oxidative stress are common pathological features of OA, the role of ferroptosis in OA has been extensively explored. Accumulating evidence indicates that iron homeostasis and lipid peroxidation are closely related to the pathogenesis of OA. This article will focus on the mechanisms of ferroptosis and the role of iron homeostasis and lipid peroxidation in the pathogenesis of OA, summarizing recent evidence.

Strategic application of imaging in DMOAD clinical trials: focus on eligibility, drug delivery, and semiquantitative assessment of structural progression.

Despite decades of research efforts and multiple clinical trials aimed at discovering efficacious disease-modifying osteoarthritis (OA) drugs (DMOAD), we still do not have a drug that shows convincing scientific evidence to be approved as an effective DMOAD. It has been suggested these DMOAD clinical trials were in part unsuccessful since eligibility criteria and imaging-based outcome evaluation were solely based on conventional radiography. The OA research community has been aware of the limitations of conventional radiography being used as a primary imaging modality for eligibility and efficacy assessment in DMOAD trials. An imaging modality for DMOAD trials should be able to depict soft tissue and osseous pathologies that are relevant to OA disease progression and clinical manifestations of OA. Magnetic resonance imaging (MRI) fulfills these criteria and advances in technology and increasing knowledge regarding imaging outcomes likely should play a more prominent role in DMOAD clinical trials. In this perspective article, we will describe MRI-based tools and analytic methods that can be applied to DMOAD clinical trials with a particular emphasis on knee OA. MRI should be the modality of choice for eligibility screening and outcome assessment. Optimal MRI pulse sequences must be chosen to visualize specific features of OA.

Causality assessment of adverse drug reaction reported in patients treated with arthritis in a tertiary care hospital: A prospective study

Background: Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory condition, initially affecting smaller joints but slowly progressing to involve larger joints. Osteoarthritis (OA) is a degenerative disease affecting mainly large joints. Pain, stiffness, and loss of mobility are the cardinal features of OA. Treatment goals of RA are pain relief, slowing the progression of joint inflammation and prevention of joint disability or deformity, whereas those of OA are immediate relief of symptoms and improving joint function. Non-steroidal anti-inflammatory drugs (NSAIDS) and disease-modifying anti-rheumatic drugs (DMARDS) are used to treat above conditions. Long treatment is associated with development of ADR. The present study aimed to evaluate the prevalence of ADR patients treating for arthritis. Aims and Objectives: The objective of the study was as follows: (i) To assess the prevalence of use of drugs and drug classes in RA and OA; (ii) to assess the prevalence of adverse events (ADE) of prescribed drugs; and (iii) causality assessment of ADE. Materials and Methods: This study was an observational study of ADE of drug prescribed among 100 arthritis patients in a tertiary care teaching hospital, India. Patients diagnosed with RA or OA with or without comorbidities were enrolled in the study based on inclusion and exclusion criteria. Causality assessment severity was assessed from Hartwig and colleagues’ criteria and preventable ADE was defined by Schumock and Thornton’s criteria. Results: Out of 100 arthritis cases, the prevalence of OA was more than RA. OA was more commonly seen in males and RA in females. Arthritis was more prevalent in the age group of 36–65 years. NSAIDs were the first-choice drug in arthritis. Among NSAIDS, diclofenac was the commonly used drug for monotherapy in OA and methotrexate was commonly used in RA. Sixty-eight ADEs were detected in 51 patients. The prevalence of ADE was 35.7%. Thirty out of 68 ADEs (44.1%) were preventable. NSAIDS and DMARDS resulted in ADEs by 23 (29.6%) and 24 (34.8%) events, respectively. Common affected organs were cutaneous manifestations, gastrointestinal tract, and eyes which accounted for 20 (29.4%), 18 (26.5%), and 8 events (11.6%), respectively. Continuation of the suspected drug was noted in 42 ADEs (61.8%), classified as severity level 1 and 2a-b, and 43 ADEs (63.2%) were completely or partially resolved during the study period. Conclusion: ADEs are common in RA and OA patients with the prevalence of 35.7%. ADEs should be monitored properly and reported to prevent irrational use of drugs.

FEATURES OF THE CLINICAL COURSE OF OSTEOARTHRITIS IN COMBINATION WITH DIABETES MELLITUS.

The aim: To examine the features of the clinical course of osteoarthritis in combination with type 2 diabetes on the background of obesity and hypertension. Materials and methods: 116 patients who were in the inpatient stage of treatment in the rheumatology department of the Chernivtsi Regional Clinical Hospital during 2015-2017 were examined. The epidemiological and clinical features of osteoarthritis in patients with type 2 diabetes mellitus were also analyzed. Results: It was found that the course of osteoarthritis is extremely severe with limited range of motion in the joints, their deformation and significant deteri¬oration of functional capacity, duration of pain, periodic prolonged exacerbations, the predominance of knee and hip injuries (64.8%) and 14.8 persons - small joints. This showed the progression and generalization of processes in various joints, aggravation of the course and prognosis of osteoarthritis, especially in women. Their prevalence was registered at II radiological stage (59.27% and 74.0%, respectively). Conclusions: The authors emphasize that such a clinical course indicates the worst prognosis. This multimorbidity of diseases requires treatment, observation and consultation with a traumatologist, rheumatologist and endocrinologist, due to the multisystem approach to the treatment and rehabilitation of such patients with an emphasis on individual clinical features (including gender) and the course of comorbidities or syndromes.

COMPUTED TOMOGRAPHY OSTEOARTHRITIS KNEE SCORE (COAKS) CONSTRUCTION, REPRODUCIBILITY AND POTENTIAL FOR STRUCTURAL PHENOTYPING

Computed tomography (CT) has been shown to be more sensitive identifying certain structural features of OA than radiography and MRI. The ability to acquire weight bearing CT (WBCT) at the knee is also an important current advantage over MRI that has created an opportunity to assess the entire weight bearing joint in 3-D. This could have implications for longitudinal monitoring of disease progression and the selection of participants in clinical trials according to structural phenotype. 1) To introduce the semi-quantitative CT OA Knee Score (COAKS); 2) to report initial interobserver reproducibility; and 3) to demonstrate its potential for structural disease phenotyping. 106 WBCT examinations were sourced from existing research projects at the Department of Rehabilitation Medicine, University of Kansas Medical Center, USA. A 4-point scoring system (0-3) was created for each cardinal radiographic feature of osteoarthritis (J = joint space width; O = osteophytes; C = subchondral cysts; S = subchondral sclerosis) to be assessed at each joint compartment (MTF = medial tibiofemoral; LTF = lateral tibiofemoral; PF = patellofemoral; PTF = proximal tibiofibular). Brief verbal definitions are given for each feature score in table 1. After initial training and grading of all knees by a musculoskeletal radiology clinical fellow (J.J.H.), a reference atlas was created that included a standardised review guide (including display settings and multiplanar reformat orientations), examples of each score for each feature at each compartment, and common pitfalls. Blinded to the imaging data, 10 test knees and 35 study knees were super-selected by their initial scoring to stratify disease features as evenly as possible. No restrictions were placed on the quality of imaging, the presence of ACL reconstruction (an inclusion criteria for one source study), or imaging review platform. T.D.T. trained another consultant musculoskeletal radiologist (Z.A.), who both assessed the 10 test knees, reviewed performance, then repeated the test assessment. Both then scored the 35 study knees without communication during the assessment period. A cloud score sheet was used in Google Sheets (table 2) with the reference atlas in Google Docs, both accessible online or via the respective smart phone / tablet app. The weighted kappa score for interobserver reproducibility was calculated for each structural feature across all compartments. Compartment feature scores were also plotted as heat maps for each knee to provide a visualisation of structural OA phenotype. The weighted kappa scores (+95% CI) for each feature were: J = 0.87 (0.86-0.89); O = 0.79 (0.76-0.82); C = 0.66 (0.63-0.70); S = 0.84 (0.82-0.86). On average, it took less than 5 minutes to score a single knee. Selected heat maps (figure 1) show how different phenotypes can be ascertained using the COAKS system: RUNA053L is an early MTF phenotype with PF involvement; RUNA045R is a late MTF phenotype with multicompartment disease; RUNA023L is a late LTF phenotype with severe multicompartmental osteophytosis but no other features; RUNA088L is a PF phenotype with small tibiofemoral osteophytes only. A whole joint COAKS score is also possible (out of 48), as is a score by compartment (out of 12) or by feature (out of 12) as desired. COAKS is a feasible semi-quantitative WBCT-based scoring system of knee OA that demonstrates initial substantial to almost perfect inter-observer agreement across radiographic features. The ability of COAKS to score and phenotype the weight bearing knee in 3-D may exceed individual capabilities of MRI and radiography in certain aspects, offering flexibility in phenotyping for patient selection as well as potential sensitivity for longitudinal monitoring of disease severity in clinical trials or cohort studies. It is also possible to use the COAKS in non-weight bearing CT if flagged as such and not used to compare with weight bearing studies.