Osteoarthritis Subjects Research Articles

The association of osteoarthritis with metabolic disorders

Osteoarthritis (OA) is the most common form of synovial joint arthritis that causes chronic pain and disability to a large number of people worldwide. Most often, osteoarthritis affects the joints of the knees, hips, spine and hands. The Global Burden of Disease (GBD, 2021) estimates that osteoarthritis will be the fourth leading cause of disability by 2030, with enormous healthcare costs for treatment, as well as significant indirect costs due to loss of productivity and premature retirement. The aim of our research is to determine in what way prevalent metabolic syndrome is among participants with osteoarthritis of one of the synovial joints (knees, hips, hands), and whether metabolic disorders are a risk factor for the development and worsening of osteoarthritis. A prospective clinical study was conducted at the Public Health Institution Health Center Živinice, from July 2022 to May 2024, on a random sample of 200 participants with a confirmed clinical diagnosis of osteoarthritis (OA), who were divided into a group with metabolic syndrome and a group without metabolic syndrome based on the NCEP ATP III panel criteria for metabolic syndrome. The prevalence of knee osteoarthritis is significantly higher compared to the prevalence of hip and hand osteoarthritis, and it is greater among participants with a higher BMI (in participants with the highest BMI, knee osteoarthritis occurs with a 100% probability) and with the presence of metabolic syndrome, especially in more severe forms, specifically radiologically confirmed osteoarthritis, regardless of age and gender. Unlike OA knees the prevalence of OA hips and hands shows no correlation with BMI and metabolic syndrome. Multiple comparative analysis of differences in the average severity of osteoarthritis of the knee of subjects with normal glycemia / prediabetes / diabetes type 2 it showed a statistically significant difference in the average severity of knee osteoarthritis in subjects with regular blood sugar compared to subjects with prediabetes/diabetes mellitus type 2 regardless of age and gender. This means that with an increase in blood sugar levels, the degree of severity of osteoarthritis of the knee increases, since each subsequent Group has a higher average value of this indicator (p<0.05; CI 95%).

The effectiveness of vitamin D supplementation in patients with end-stage knee osteoarthritis: Study protocol for a double-blinded, randomized controlled trial.

Osteoarthritis (OA) knee is one of the most common chronic degenerative conditions that imposes clinical and economic burdens on individuals and societies worldwide. Previous studies showed vitamin D levels correlated positively with lean muscle mass and grip strength, implying that vitamin D supplementation may improve muscle health in knee OA subjects. This randomized controlled trial (RCT) aims to compare the effects of vitamin D supplementation on knee muscle strength, physical function, pain, and sarcopenia status in patients with end-stage knee OA. Patients and outcome assessors will be blinded to group allocation. Fifty-six end-stage knee OA patients with vitamin D insufficiency fulfilling our inclusion criteria will be invited to participate in this study. Patients will be randomly assigned to take vitamin D supplementation (4,000 IU capsule daily) or placebo for six months. Measurements will be taken at baseline, three and six-month after the commencement of the vitamin D supplement, and 6-month after the interventional period. The primary outcome includes the isometric quadriceps and hamstring muscle strength measured by a hand-held dynamometer. Secondary outcomes include pain, performance-based and self-reported physical function and sarcopenia status. The success of this study will provide scientific evidence of whether the relatively cheap and well-tolerated vitamin D supplement can improve quadriceps muscle strength, physical function, pain symptoms, and sarcopenia status of this increasingly large population for end-stage knee OA patients. The study has great clinical significance given Hong Kong's lengthy and growing waiting list for complete knee replacement procedures. Trial registration: The trial was registered on clinicaltrials.gov (NCT05981534) on 31st July 2023.

The effects of pulsed electromagnetic field therapy on muscle strength and pain in patients with end-stage knee osteoarthritis: a randomized controlled trial.

Osteoarthritis (OA) of the knee is one of the most common chronic degenerative joint conditions affecting aging population. To investigate the effectiveness of a combination of home-based exercise and pulsed electromagnetic field (PEMF) therapy to improve muscle strength, physical function, and pain. Sixty patients were randomly assigned to either home-based exercise alone (control group; n = 30) or combined with PEMF therapy (treatment group; n = 30) twice a week for eight weeks. Knee extension, flexion muscle strength, gait speed (GS), 5 time sit-to-stand test (5STS), Visual Analogue Scale (VAS) pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and 4 and 8 weeks. Significant improvements in symptomatic knee extension muscle strength (SKE, p = 0.001), flexion strength (SKF, p = 0.011), contralateral knee extension muscle strength (CKE, p = 0.002), and flexion strength (CKF, p = 0.009) were observed for the PEMF treatment group at 8 weeks. Significant reductions in VAS pain scores were observed in both the treatment (p < 0.001, partial η2 = 0.505) and control (p < 0.001, partial η2 = 0.268) groups. Significant differences were reported between groups in the 4 (p = 0.010, partial η2 = 0.111) and 8 (p = 0.046, partial η2 = 0.068) week assessment in VAS pain. A significant time difference was found in GS and 5STS between baseline and week 8 (GS: difference 0.051, p = 0.026; 5STS: difference 2.327, p < 0.001) in the treatment group. The significant group difference at week 8 was observed in SKE (p = 0.013) in female patients while pain in male patients (p = 0.026). Patients aged over 70 years have a significantly superior improvement in SKE, SKF, and CKF after 8 weeks of PEMF therapy. The combination of PEMF therapy and home-based exercise superiorly improved knee muscle strength and reduced pain in end-stage knee OA subjects and showed a promising tendency to improve performance-based physical function. PEMF therapy was shown to preferentially benefit knee muscle strength in female patients and patients aged over 70 years, whereas male patients were more responsive to PEMF therapy in the form of pain relief. clinicalTrials.gov, NCT05550428.

Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis

Selenoprotein P (SELENOP) controls selenium (Se) transport, and glutathione peroxidase 3 (GPx3) elicits antioxidant activity in blood. Inflammation associates with Se deficiency, but knowledge concerning selenoproteins in inflammatory rheumatic musculoskeletal diseases (iRMD) is limited. We compared three Se biomarkers in patients with rheumatoid (RA), psoriatic (PsA), and juvenile idiopathic arthritis (JIA) in comparison to osteoarthritis (OA) and healthy subjects, to improve the data base on selenoprotein expression in iRMD.The cross-sectional study enrolled n=272 patients with RA (n=131), PsA (n=67), JIA (n=22) and OA (n=52). Serum Se was quantified by total reflection X-ray fluorescence, SELENOP by ELISA and GPx3 by an enzymatic test. Data from the EPIC trial served as reference. Impairment of daily life was assessed by the Functional Ability Questionnaire (FfbH).Serum SELENOP and Se concentrations correlated linearly in all groups and were below the average measured in EPIC. Se concentration was not different between the patient groups. Compared to controls, SELENOP levels were low in iRMD patients. GPx3 activity was particularly low in JIA and PsA. Seropositive but not seronegative RA patients displayed a disrupted interaction between GPx3 and Se or SELENOP. SELENOP associated with the functional status measured by the FfbH, most pronounced in OA (R=0.76, P < .01).The data indicate selenoprotein deficiency in the majority of patients with iRMD, and a positive relation of SELENOP with functional status in OA. Since increased Se supply improves selenoprotein biosynthesis, a personalized correction of diagnosed deficiency merits consideration to improve Se transport and ameliorate disease burden.

Comparison of Gait in Women with Degenerative Changes of the Hip Joint and Healthy Women Using the MoKA System-A Pilot Study.

Osteoarthritis (OA) is a global problem. There are few reports in the literature regarding the temporal and spatial parameters of gait in people with OA. The aim of this study was to determine spatiotemporal parameters for the pelvis and lower limbs during walking in women with OA and to compare these parameters with healthy people. For this purpose, a 6 min walking test (6MWT) was carried out. OA subjects had worse outcomes compared to the control group (p < 0.05). Data were collected using IMU sensors integrated into the MoKA system and mounted on indicator points on the body. Limited mobility of the pelvis in the frontal plane was observed in the study group, which influenced walking strategy. For the comparison with the control group at each minute, p < 0.05. IMU sensors attached to the body and integrated in one application provide extensive research and diagnostic capabilities.

The combined effect of transcutaneous electrical nerve stimulation and transcutaneous auricular vagus nerve stimulation on pressure and heat pain thresholds in pain-free subjects: a randomized cross-over trial

BackgroundTranscutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects.Methods/designThe study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p < 0.05.DiscussionThis study will provide evidence concerning the combined effects of TENS and TaVNS on pain threshold in pain-free participants. Based on the outcomes, a greater understanding of how TENS and TaVNS, when used in conjunction, can modulate pain pathways.Trial registrationClinicalTrials.gov NCT06361381. Registered on 09 April 2024.

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.

Digital wearable insole-based identification of knee arthropathies and gait signatures using machine learning.

Gait is impaired in musculoskeletal conditions, such as knee arthropathy. Gait analysis is used in clinical practice to inform diagnosis and monitor disease progression or intervention response. However, clinical gait analysis relies on subjective visual observation of walking as objective gait analysis has not been possible within clinical settings due to the expensive equipment, large-scale facilities, and highly trained staff required. Relatively low-cost wearable digital insoles may offer a solution to these challenges. In this work, we demonstrate how a digital insole measuring osteoarthritis-specific gait signatures yields similar results to the clinical gait-lab standard. To achieve this, we constructed a machine learning model, trained on force plate data collected in participants with knee arthropathy and controls. This model was highly predictive of force plate data from a validation set (area under the receiver operating characteristics curve [auROC] = 0.86; area under the precision-recall curve [auPR] = 0.90) and of a separate, independent digital insole dataset containing control and knee osteoarthritis subjects (auROC = 0.83; auPR = 0.86). After showing that digital insole-derived gait characteristics are comparable to traditional gait measurements, we next showed that a single stride of raw sensor time-series data could be accurately assigned to each subject, highlighting that individuals using digital insoles can be identified by their gait characteristics. This work provides a framework for a promising alternative to traditional clinical gait analysis methods, adds to the growing body of knowledge regarding wearable technology analytical pipelines, and supports clinical development of at-home gait assessments, with the potential to improve the ease, frequency, and depth of patient monitoring.

Prognostic model to predict the incidence of radiographic knee osteoarthritis

ObjectiveEarly diagnosis of knee osteoarthritis (KOA) in asymptomatic stages is essential for the timely management of patients using preventative strategies. We develop and validate a prognostic model useful for predicting...

Lateral distal femoral condyle has more uniform cartilage wear in varus knee osteoarthritis

Bone resection is highly valued in total knee arthroplasty (TKA), but how to determine the amount of distal femur resection is still controversial. The purpose of this study was to explore how to use lateral condyle as a reference for distal femoral osteotomy in TKA. Magnetic resonance imaging (MRI) and Radiographic images from 118 nonarthritic subjects and 123 osteoarthritis (OA) subjects were used to assess the cartilage wear pattern of the distal femur in varus knees. Measurements were performed on three-dimensional reconstruction after virtual bone cutting. The difference between the resection amount of distal (0°) and posterior (90°) was calculated when the medial condyle was used as a reference in OA patients. The osteotomy amount on lateral was calculated in nonarthritic subjects when the medial condylar osteotomy was consistent with the thickness of the implants. In 43% of OA patients, there was > 1 mm difference between the 0° and 90° in medial condyle cartilage, and no difference was observed in lateral. When using medial condyle as a reference for osteotomy, there was a difference of 1.3 ± 0.56 mm between the resection amount of 0° and 90°, and the difference was 0.24 ± 0.27 mm when using lateral condyle. Statistical analysis showed that there was a linear correlation between the resection amount of lateral condyle and mechanical lateral distal femoral angle (mLDFA) in nonarthritic subjects (r = 0.845, p < 0.001). Lateral distal femoral condyle has more uniform cartilage wear in varus knee osteoarthritis. Using the lateral condyle as the reference for distal femoral osteotomy is more suitable for the cartilage wear pattern of the varus knee. The position of cutting guide can be adjusted by preoperative measurements of mLDFA.

Effect of a Sensorimotor Training on Pain, Proprioception, and Functional Activities in Participants with Chronic Knee Osteoarthritis: A Randomized Controlled Clinical Trial

Background: Knee osteoarthritis (OA) is a chronic, debilitating condition that significantly impairs functional health status among affected individuals. Key challenges associated with chronic knee OA include persistent pain, diminished functional capabilities, and compromised balance. These factors highlight the critical need for effective intervention strategies. Recent research suggests that sensorimotor training may play a pivotal role in addressing these issues. However, there remains a gap in the literature regarding the specific effects of sensorimotor training on pain perception, proprioception, and overall functional levels in this population. Therefore, the aim of this study was to systematically investigate the impact of sensorimotor training on pain, proprioceptive abilities, and functional performance in individuals with chronic knee OA. Methods: Total 66 patients with chronic knee OA were divided into two equal groups. The control group received a traditional exercise programme and the experimental group received sensorimotor training in addition to traditional exercises. Blind assessment was conducted at the beginning of the study and after 4 weeks of training to measure pain by NPRS, proprioception acuity by passive – active joint position reproduction method, and functional disability by TUG &amp; KOOS scale. Statistical analysis was performed using SPSS 23. Data were presented as mean, standard deviation (SD) and mean difference. Within groups compare we used Paired t test and between groups compare we used Independent t test with post data comparison in SPSS. The significance level was set at (p&lt;0.05). Result: For experimental group and control group statistical significant (p&lt;0.05) improvements were recorded in all measured parameters. Mean difference of KOOS in control group is 5.97% and experimental group is 17.63% and in mean difference of pain in control group is 2.33 and experimental group is 3.88 which shows that SMT is very effective than traditional exercise only. According to MCID of all outcomes, pain, KOSS and TUG test is clinically significant. The sensorimotor group produced significantly better improvement than the traditional group. Conclusion: Sensorimotor training along with traditional exercises is more effective then only traditional exercises for patients with chronic knee OA. The addition of sensorimotor training to traditional strengthening and stretching exercises could provide more motor control and help neuromuscular restoration of balance and subsequently improve the functional level of chronic knee OA subjects.

Differential Metabolites in Osteoarthritis: A Systematic Review and Meta-Analysis.

(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and high-level evidence is still lacking. In this study, we performed a systematic review and meta-analysis of differential small molecule metabolites between OA patients and healthy individuals to screen promising candidates from a large number of samples with the aim of informing future prospective studies. (2) Methods: We searched the EMBASE, the Cochrane Library, PubMed, Web of Science, Wan Fang Data, VIP Date, and CNKI up to 11 August 2022, and selected relevant records based on inclusion criteria. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. We performed qualitative synthesis by counting the frequencies of changing directions and conducted meta-analyses using the random effects model and the fixed-effects model to calculate the mean difference and 95% confidence interval. (3) Results: A total of 3798 records were identified and 13 studies with 495 participants were included. In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts. Among them, 37 metabolites appeared more than twice. The results of meta-analyses among four studies showed that three metabolites increased, and eight metabolites decreased compared to healthy controls (HC). (4) Conclusions: The main differential metabolites between OA and healthy subjects were amino acids (AAs) and their derivatives, including tryptophan, lysine, leucine, proline, phenylalanine, glutamine, dimethylglycine, citrulline, asparagine, acetylcarnitine and creatinine (muscle metabolic products), which could be potential biomarkers for predicting OA.

Inflammatory biomarkers in patients with painful knee osteoarthritis: exploring the potential link to chronic postoperative pain after total knee arthroplasty-a secondary analysis.

Total knee arthroplasty (TKA) is the end-stage treatment of knee osteoarthritis (OA), and approximately 20% of patients experience chronic postoperative pain. Studies indicate that inflammatory biomarkers might be associated with pain in OA and potentially linked to the development of chronic postoperative pain after TKA. This study aimed to (1) evaluate preoperative serum levels of inflammatory biomarkers in patients with OA and healthy control subjects, (2) investigate preoperative differences of inflammatory biomarker profiles in subgroups of patients, and (3) compare subgroups of patients with and without postoperative pain 12 months after surgery. Serum samples from patients with OA scheduled for TKA (n = 127) and healthy participants (n = 39) were analyzed. Patients completed the Knee-injury-and-Osteoarthritis-Outcome-Score (KOOS) questionnaire and rated their clinical pain intensity using a visual analog scale (VAS) before and 12 months after TKA. Hierarchical cluster analysis and Orthogonal Partial Least Squares Discriminant Analysis were used to compare groups (patients vs control subjects) and to identify subgroups of patients in relation to postoperative outcomes. Difference in preoperative and postoperative VAS and KOOS scores were compared across subgroups. Twelve inflammatory markers were differentially expressed in patients when compared with control subjects. Cluster analysis identified 2 subgroups of patients with 23 proteins being significantly different ( P < 0.01). The 12-months postoperative VAS and KOOS scores were significantly different between subgroups of patients ( P < 0.05). This study identified differences in specific inflammatory biomarker profiles when comparing patients with OA and control subjects. Cluster analysis identified 2 subgroups of patients with OA, with one subgroup demonstrating comparatively worse 12-month postoperative pain intensity and function scores.

Efficacy and Safety of Undenatured Type II Collagen in The Treatment of Osteoarthritis of The Knee: A Randomized, Double-blind, Placebo-controlled Trial

BACKGROUND: Available medication for pain and joint stiffness release in osteoarthritis (OA) often gives considerable side effects. Undenatured type II collagen (UC-II) has been considered as a treatment for OA for its ability to prevent the progress of articular cartilage damage. Hence, this study aimed to evaluate the efficacy and safety of UC-II in modulating knee joint function.METHODS: This was a randomized, double-blind, placebo-controlled study involving 102 OA subjects. Subjects were randomized into two groups: receiving an oral daily dose of 40 mg/day UC-II or placebo containing microcrystalline cellulose for 90 days. Efficacy was evaluated by using the Western Ontario McMaster Osteoarthritis Index (WOMAC), Lequesne’s Functional Index (LFI), and Visual Analogue Scale (VAS) score on day-1, -7, -30, -60, and -90. Safety was evaluated by assessing the adverse events (AEs) and abnormal laboratory findings.RESULTS: The WOMAC total score showed a significant difference between the UC-II group vs. the placebo group from day-7 (p&lt;0.05) to day-90 (p&lt;0.01). UC-II was more effective in reducing the WOMAC total scores by 81.6% compared to 19.2% in the placebo group after 90 days. The total LFI and VAS score was significantly reduced in subjects supplemented with UC-II compared to the placebo group (75.8% vs. 7.8%; 67.9% vs. 12.2%, respectively). No significant changes were observed in vital signs and clinical laboratory tests compared to the placebo. The UC-II had a good safety profile with no serious adverse events among participants.CONCLUSION: UC-II significantly improved the knee pain, stiffness, and functional mobility of OA patients and was well-tolerated.KEYWORDS: osteoarthritis, undenatured type II collagen, WOMAC, VAS, LFI

Efficacy of a proprietary combination of Tamarindus indica seeds and Curcuma longa rhizome extracts in osteoarthritis: a clinical investigation.

NXT15906F6 (TamaFlex™) is a proprietary blend containing standardized Tamarindus indica seeds and Curcuma longa rhizome extracts. Earlier, NXT15906F6 supplementation demonstrated reduced knee joint pain and improved musculoskeletal functions in healthy and knee osteoarthritis (KOA) subjects. The present randomized, double-blind, placebo-controlled study was focused on validating the clinical efficacy of NXT15906F6 in a larger number of subjects with KOA. Male and female subjects (age: 40-70 years; body mass index [BMI]: 20-29 kg/m2] were randomized into three groups receiving placebo (n = 50), NXT15906F6 (n = 50) or a blend of C. longa and Boswellia serrata extracts (CLBS) (n = 50). Subjects consumed 250 mg NXT15906F6, 1,000 mg CLBS or a matched placebo daily after breakfast over a period of 30 consecutive days. The primary efficacy outcome was the improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and the secondary efficacy measures included various tests on joint pain and musculoskeletal functions and evaluations ofserum high-sensitivity C-reactive protein (hs-CRP) and a cartilage degradation marker, C-terminal telopeptide of type II collagen in urine (uCTX-II). NXT15906F6 significantly (P < 0.001) reduced the WOMAC scores and improved musculoskeletal function scores in the participants as compared with baseline and placebo. NXT15906F6 participants reduced knee pain and improved musculoskeletal functions as early as day 5 of supplementation. In contrast, CLBS supplementation failed to show early efficacies in pain and functional scores, except for 30s-CST and primary knee flexion. The NXT1506F6-supplemented participants significantly reduced serum hs-CRP and uCTX-II levels from baseline and as compared with the placebo. Both supplementations did not alter the subjects' clinical chemistry, hematology, and vital parameters. The anti-inflammatory botanical composition NXT15906F6 supplementation mitigated joint pain and improved musculoskeletal functions and joint motility in KOA subjects. This botanical composition was also well-tolerated by the volunteers.

A Blend of Tamarindus Indica and Curcuma Longa Extracts Alleviates Monosodium Iodoacetate (MIA)-Induced Osteoarthritic Pain and Joint Inflammation in Rats

Background and objective NXT15906F6 (TamaFlexTM) is a proprietary herbal composition containing Tamarindus indica seeds and Curcuma longa rhizome extracts. NXT15906F6 supplementation has been shown clinically effective in reducing knee joint pain and improving musculoskeletal functions in healthy and knee osteoarthritis (OA) subjects. The objective of the present study was to assess the possible molecular basis of the anti-OA efficacy of NXT15906F6 in a monosodium iodoacetate (MIA)-induced model of OA in rats. Methods Healthy male Sprague Dawley rats (age: 8–9 wk body weight, B.W.: 225–308 g (n = 12) were randomly assigned to one of the six groups, (a) vehicle control, (b) MIA control, (c) Celecoxib (10 mg/kg B.W.), (d) TF-30 (30 mg/kg B.W.), (e) TF-60 (60 mg/kg B.W.), and (f) TF-100 (100 mg/kg B.W.). OA was induced by an intra-articular injection of 3 mg MIA into the right hind knee joint. The animals received either Celecoxib or TF through oral gavage over 28 days. The vehicle control animals received intra-articular sterile normal saline. Results Post-treatment, NXT15906F6 groups showed significant (p < 0.05) dose-dependent pain relief as evidenced by improved body weight-bearing capacity on the right hind limb. NXT15906F6 treatment also significantly reduced the serum tumor necrosis factor-α (TNF-α, p < 0.05) and nitrite (p < 0.05) levels in a dose-dependent manner. mRNA expression analyses revealed the up-regulation of collagen type-II (COL2A1) and down-regulation of matrix metalloproteinases (MMP-3, MMP-9 and MMP-13) in the cartilage tissues of NXT15906F6-supplemented rats. Cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) protein expressions were down-regulated. Decreased immunolocalization of NF-κβ (p65) was observed in the joint tissues of NXT15906F6-supplemented rats. Furthermore, microscopic observations revealed that NXT15906F6 preserved MIA-induced rats’ joint architecture and integrity. Conclusion NXT15906F6 reduces MIA-induced joint pain, inflammation, and cartilage degradation in rats.

FINITE ELEMENT ANALYSIS OF CUSTOMIZED KNEE IMPLANTS BY VARYING LOADS DURING FLEXION-EXTENSION MOVEMENT

A customized knee implant numerical modeling using finite element analysis (FEA) during flexion extension has been investigated in this paper with varying loads with an objective of studying its kinematics. Computed tomography (CT) images of 15 osteoarthritis subjects’ images were used in this work. Various morphological characteristics were extracted from clinical images using a commercial CAE software and biomechanical properties were studied on applying standard loads on customized implant and off-the-shelf (OTS) implants. Patient-specific knee implants have been designed according to the morphological characteristics and bone dimension of patient with compressive loads (1500, 1700 and 3000[Formula: see text]N) during normal gait and were compared with the normal knee. Results showed that the stresses are distributed equally to the spacer and the tibial plate, unlike the standard femoral component where the stresses get concentrated on the cut edges. In compressive load, active stress and strain ([Formula: see text]–20[Formula: see text]MPa) are lesser ([Formula: see text]) and in flexion extension also lesser with a scaling factor of 0.785 and 1.0. The designed implant was found to produce similar biomechanical properties when compared to normal knee joint and thus it can be considered as a valuable implant and could replace the standard OTS knee implants.

A discriminative shape-texture convolutional neural network for early diagnosis of knee osteoarthritis from X-ray images.

Knee Osteoarthritis (OA) is one of the most common causes of physical disability worldwide associated with a significant personal and socioeconomic burden. Deep Learning approaches based on Convolutional Neural Networks (CNNs) achieved remarkable improvements in knee OA detection. Despite this success, the problem of early knee OA diagnosis from plain radiographs remains a challenging task. This is due to the high similarity between the X-ray images of OA and non-OA subjects and the disappearance of texture information regarding bone microarchitecture changes in the top layers during the learning process of the CNN models. To address these issues, we propose a Discriminative Shape-Texture Convolutional Neural Network (DST-CNN), which automatically diagnoses early knee OA from X-ray images. The proposed model incorporates a discriminative loss to improve class separability and deal with high inter-class similarities. In addition, a new Gram Matrix Descriptor (GMD) block is embedded in the CNN architecture to compute texture features from several intermediate layers and combine them with the shape features in the top layers. We show that merging texture features with deep ones leads to better prediction of the early stages of OA. Comprehensive experimental results on two large public databases, Osteoarthritis Initiative (OAI) and Multicenter Osteoarthritis Study (MOST) demonstrate the potential of the proposed network. Ablation studies and visualizations are provided for a detailed understanding of our proposed approach.

Systemic inflammation response index as an emerging biomarker in osteoarthritis patients: a bibliometric and large sample retrospective investigation.

To determine the value of the whole-blood inflammatory response index as an emerging biomarker for the assessment of disease activity in osteoarthritis (OA). Extensive analysis of the literature on OA and whole-blood inflammatory indicators were provided through a bibliometric approach. Clinical characteristics and indicators of OA patients and healthy controls (HC) were retrospectively analysed. Four whole-blood inflammatory response indices - neutrophil/lymphocyte count (NLR), platelet/lymphocyte count (PLR), monocyte/lymphocyte count (MLR), and systemic inflammation response index (SIRI), as well as clinical traits like the OA patient's self-perception and immune-inflammatory indicators were analysed for correlations. Cut-off values were determined using receiver operating characteristic (ROC) curves, and they were subsequently employed in logistic regression models to work out whole-blood inflammatory indices and disease activity. The pathophysiology of osteoarthritis has received most of the spotlight in literature studies of OA and whole-blood inflammation indicators. The "inflammation", "osteoarthritis" and "disease activity" were the top 3 key word clusters. Retrospective analysis showed that MLR, NLR, PLR, and SIRI were markedly higher in OA subjects compared to HC subjects. ROC curve consequences manifested that SIRI and NLR could separate OA from healthy controls. NLR, PLR, MLR, and SIRI proved to be related to immune-inflammatory markers, visual analogue scale (VAS) scores, and short-form (SF)-36 scores with regard to correlation analysis and association criteria. Logistic regression manifested that SIRI, NLR, and C-reactive protein (CRP) forecasted disease activity, however, the model that combined SIRI and CRP was superior to CRP alone. SIRI may serve as a non-invasive, appropriate biomarker to correlate with disease activity.

Defective chaperone-mediated autophagy is a hallmark of joint disease in patients with knee osteoarthritis

Defects in autophagy contribute to joint aging and Osteoarthritis (OA). Identifying specific autophagy types could be useful for developing novel treatments for OA. An autophagy-related gene array was performed in blood from non-OA and knee OA subjects from the Prospective Cohort of A Coruña (PROCOAC). The differential expression of candidate genes was confirmed in blood and knee cartilage and a regression analysis was performed adjusting for age and BMI. HSP90A, a chaperone mediated autophagy (CMA) marker was validated in human knee joint tissues, as well as, in mice with aging-related and surgically-induced OA. The consequences of HSP90AA1 deficiency were evaluated on OA pathogenesis. Finally, the contribution of CMA to homeostasis was studied by assessing the capacity to restore proteostasis upon ATG5-mediated macroautophagy deficiency and genetic HSP90AA1 overexpression. 16 autophagy-related genes were significantly down-regulated in blood from knee OA subjects. Validation studies showed that HSP90AA1 was down-regulated in blood and human OA cartilage and correlated with risk incidence of OA. Moreover, HSP90A was reduced in human OA joints tissues and with aging and OA in mice. HSP90AA1 knockdown was linked to defective macroautophagy, inflammation, oxidative stress, senescence and apoptosis. However, macroautophagy deficiency increased CMA, highlighting the CMA-macroautophagy crosstalk. Remarkably, CMA activation was sufficient to protect chondrocytes from damage. We show that HSP90A is a key chaperone for chondrocyte homeostasis, while defective CMA contributes to joint damage. We propose that CMA deficiency is a relevant disease mechanism and could represent a therapeutic target for OA.