Osteoarthritis Status Research Articles

A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip

BackgroundPain associated with osteoarthritis (OA) is frequently disabling; treatments are often ineffective or intolerable. Fasinumab selectively inhibits nerve-growth factor and has shown efficacy for the management of OA pain. MethodsIn this randomized, double-blind, phase III safety study, patients with moderate-to-severe OA pain and history of inadequate pain relief received placebo or fasinumab (at 1, 3, 6, and 9 ​mg every 4 weeks [Q4W] and 1 and 6 ​mg every 8 weeks [Q8W] for 52 weeks). Primary safety endpoints included adverse events, adjudicated arthropathies (AAs), and joint replacements (JRs). Co-primary endpoints of an efficacy sub-study were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores. During the study, higher fasinumab doses were discontinued for safety; 1 ​mg doses continued. ResultsOf 13,945 patients screened, 5331 were randomized; 1074 were included in the efficacy sub-study. AAs and JRs occurred in all groups. Increased severity of disease at baseline was associated with higher rates of AAs and JRs. A dose-dependent risk of AA or JR was observed for fasinumab; in the 1 ​mg groups, only a small percentage of patients with JR had prior AA. Fasinumab significantly improved WOMAC pain and physical function scores compared with placebo; least squares mean differences versus placebo were −1.22 and ​−1.20 for 1 ​mg Q4W and −0.73 and ​−0.74 for 1 ​mg Q8W, respectively (P<0.001). ConclusionAAs and JRs showed a dose relationship to fasinumab and were associated with baseline OA status. Fasinumab achieved statistically significant improvements in WOMAC pain and physical function scores compared with placebo.

Association between sarcopenic obesity and osteoarthritis: The potential mediating role of insulin resistance

BackgroundSarcopenic obesity (SO) and osteoarthritis (OA) are highly prevalent musculoskeletal conditions that significantly impair health-related quality of life. AimThis study investigated the association between SO and OA, and explored the potential mediating role of insulin resistance in this relationship. We utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. MethodsThis cross-sectional analysis employs NHANES data collected from 1999 to 2018, including participants aged 18 years and older. SO was assessed using dual-energy X-ray absorptiometry (DXA) measurements. Insulin resistance was estimated using the triglyceride-glucose (TyG) index. OA status was based on self-reported physician diagnosis. Statistical analyses included weighted logistic regression, restricted cubic spline (RCS) interaction analysis, mediation analysis using structural equation modeling (SEM), and receiver operating characteristic (ROC) curve analysis. Subgroup analyses were conducted based on age, sex, and diabetes status. ResultsThe sarcopenic obese group demonstrated the highest prevalence of OA (23.4 %), hypertension (47.8 %), and diabetes (12.0 %). Additionally, they exhibited elevated levels of triglycerides, cholesterol, glucose, blood urea nitrogen (BUN), creatinine, and uric acid. Logistic regression revealed significant positive associations between sarcopenic obesity, the TyG index, and OA risk. RCS analysis identified significant non-linear relationships and interactions of the TyG index with age, sex, and diabetes status on OA risk. Mediation analysis indicated that the TyG index mediated approximately 4.9 % of the effect of sarcopenic obesity on OA risk. ROC curve analysis demonstrated moderate diagnostic accuracy for the TyG index (AUC = 0.65), which improved when incorporated into the multivariate model (AUC = 0.78). Subgroup analyses confirmed significant associations between the TyG index and sarcopenic obesity with OA risk across different age, sex, and diabetes status categories. ConclusionOur findings suggest a significant correlation between insulin resistance, as measured by the TyG index, and elevated OA risk in individuals with sarcopenic obesity. Targeting insulin resistance through future research may be a promising avenue to lower OA risk in this population.

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.

Temperature‐Activated Near‐Infrared‐II Fluorescence and SERS Dynamic‐Reversible Probes for Long‐Term Assessment of Osteoarthritis In Vivo

AbstractThe abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real‐time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature‐activated near‐infrared‐II fluorescence (NIR‐II FL) and surface‐enhanced Raman scattering (SERS) nanoprobe for long‐term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR‐II FL dye was grafted onto the surface of nanoporous core‐satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR‐II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real‐time evaluation of therapeutic effects.

Temperature-Activated Near-Infrared-II Fluorescence and SERS Dynamic-Reversible Probes for Long-Term Assessment of Osteoarthritis In Vivo.

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

Knee Arthroscopic Surgery in Middle-Aged Patients With Meniscal Symptoms: A 10-Year Follow-up of a Prospective, Randomized Controlled Trial

Background: Short- and midterm evaluations of arthroscopic meniscal surgery have shown little or no effect in favor of surgery, although long-term effects, including radiographic changes, are unknown. Purpose: To compare the 10-year outcomes in middle-aged patients with meniscal symptoms between a group that received an exercise program alone and a group that received knee arthroscopy in addition to the exercise program with respect to the prevalence of radiographic and symptomatic osteoarthritis (OA), patient-reported outcomes, and clinical status. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 179 eligible patients aged 45 to 64 years, 150 were randomized to undergo either 3 months of exercise therapy (nonsurgery group) or knee arthroscopy in addition to the exercise therapy (surgery group). Surgery usually consisted of partial meniscectomy (n = 56) or diagnostic arthroscopy (n = 8). Radiographs were assessed according to the Kellgren-Lawrence score at the baseline and 5- and 10-year follow-ups. Patient-reported outcome measures were reported at the baseline and 1-, 3-, 5-, and 10-year follow-ups. Clinical status was assessed at a 10-year follow-up. The primary outcomes were radiographic OA and changes in the Knee injury and Osteoarthritis Outcome Score Pain subscale (KOOSPAIN) from the baseline to the 10-year follow-up. The primary analysis was performed using the intention-to-treat approach. Results: At the time of the 10-year follow-up, eight patients had died, leaving 142 eligible patients. Radiographic OA was assessed for 95 patients (67%), questionnaires were answered by 110 (77%), and the clinical status was evaluated for 95 (67%). Radiographic OA was present in 67% of the patients in each group (P≥ .999); symptomatic OA was present in 47% of the nonsurgery group and 57% of the surgery group (P = .301). There were no differences between groups regarding changes from baseline to 10 years in any of the KOOS subscales. Conclusion: Knee arthroscopic surgery, in most cases consisting of partial meniscectomy or diagnostic arthroscopy, in addition to exercise therapy in middle-aged patients with meniscal symptoms, did not increase the rates of radiographic or symptomatic OA and resulted in similar patient-reported outcomes at the 10-year follow-up compared with exercise therapy alone. Considering the short-term benefit and no long-term harm from knee arthroscopic surgery, the treatment may be recommended when first-line treatment—including exercise therapy for ≥3 months—does not relieve patient’s symptoms. Registration: Clinical Trials NCT01288768 (ClinicalTrials.gov identifier).

Cachexia in preclinical rheumatoid arthritis: Longitudinal observational study of thigh magnetic resonance imaging from osteoarthritis initiative cohort.

Preclinical rheumatoid arthritis (Pre-RA) is defined as the early stage before the development of clinical RA. While cachexia is a well-known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre-RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre-RA with the matched controls. In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre-RA and propensity score (PS)-matched control groups. Pre-RA was retrospectively defined as the absence of RA from baseline to year-2, with progression to physician-diagnosed clinical RA between years 3-8 of the follow-up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year-2 follow-ups of the cohort. The outcomes were the differences between Pre-RA and control groups in the 2-year rate of change for thigh muscle composition [cross-sectional area (CSA) and intramuscular adipose tissue (Intra-MAT)] and adiposity [intermuscular adipose tissue (Inter-MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed-effect regression models were used for comparison. After 1:3 PS-matching of the groups for confounding variables (demographics, risk factors, co-morbidities, and knee osteoarthritis status), 408 thighs (102 Pre-RA and 306 control) of 322 participants were included (age mean±SD: 61.7±8.9years; female/male: 1.8). Over a 2-year period, Pre-RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): -180.13mm2/2-year, -252.80 to -107.47, P-value<0.001]. Further examination of thigh muscle composition showed that the association of the presence of Pre-RA with a larger decrease in muscle CSA over 2years was noticeable in the quadriceps, flexors, and sartorius muscle groups (P-values<0.05). Comparison of changes in total adipose tissue showed no difference between Pre-RA and control participants (estimate, 95% CI: 48.48mm2/2-year, -213.51 to 310.47, P-value=0.691). However, in the detailed analysis of thigh adiposity, Pre-RA presence was associated with a larger increase in Inter-MAT (estimate, 95% CI: 150.55mm2/2-year, 95.58 to 205.51, P-value<0.001). Preclinical rheumatoid arthritis is associated with a decrease in muscle cross-sectional area and an increase in intermuscular adipose tissue, similar to rheumatoid cachexia in clinical rheumatoid arthritis. These findings suggest the presence of cachexia in the preclinical phase of rheumatoid arthritis. Given that cachexia, which can exacerbate health outcomes, is potentially modifiable, this study emphasizes the importance of early identification of patients in their preclinical phase.

Characterizing Osteophyte Formation in Knee Osteoarthritis: Application of Machine Learning Quantification of a Computerized Tomography Cohort: Implications for Treatment

BackgroundOsteophytes are commonly used to diagnose and guide knee osteoarthritis (OA) treatment, but their causes are unclear. Although they are not typically the focus of knee arthroplasty surgeons, they can predict case difficulty and length. Furthermore, their extent and location may yield much information about the knee joint status. The aims of this computed tomography–based study in patients awaiting total or partial knee arthroplasty were to: (1) measure osteophyte volume in anatomical subregions and relative change as total volume increases; (2) determine whether medial and/or lateral OA affects osteophyte distribution; and (3) explore relationships between osteophytes and OA severity. MethodsData were obtained from 4,928 computed tomography scans. Machine-learning-based imaging analyses enabled osteophyte segmentation and quantification, divided into anatomical regions. Mean three-dimensional joint space narrowing was assessed in medial and lateral compartments. A Bayesian model assessed the uniformity of osteophyte distribution. We correlated femoral osteophyte volumes with B-scores, a validated OA status measure. ResultsTotal tibial (25%) and femoral osteophyte volumes (75%) within each knee correlated strongly (R2 = 0.85). Medial osteophytes (65.3%) were larger than lateral osteophytes (34.6%), with similar proportions in both the femur and tibia. Osteophyte growth was found in all compartments, and as total osteophyte volume increased, the relative distribution of osteophytes between compartments did not markedly change. No evidence of variation was found in the regional distribution of osteophyte volume between knees with medial, lateral, both, or no three-dimensional joint space narrowing in the femur or tibia. There was a direct relationship between osteophyte volume and OA severity. ConclusionsOsteophyte volume increased in both medial and lateral compartments proportionally with total osteophyte volume, regardless of OA location. The peripheral position of femoral osteophytes does not appear to contribute to load-bearing. This suggests that osteophytic growth represents a ‘whole-knee’/global response. This work may have broad applications for knee OA, both surgically and nonoperatively.

A Predictive Modeling for Characterization and Grading of Knee Osteoarthritis Using Machine Learning Algorithms: A Study in Early Diagnosis and Prognosis

Osteoarthritis (OA), particularly knee osteoarthritis, is the most prevalent form of arthritis, resulting in severe dis-ability for sufferers throughout the world. A Manual diagnosis, segmentation, and annotating joints of knee continue to be the most used procedure for diagnosing osteoarthritis (OA) in clinical settings, despite being laborious and highly susceptible to user variation. Several prediction models displayed prognostic ability in ways of predicting the possible onset of OA, the potential aggravation of OA, the prospective progression of pain and structural deterioration as well as the potential occurrence of total knee replacement (TKR). Apart from research gaps, techniques of machine learning continue to demonstrate enormous potential for challenging tasks e.g., initial knee OA detection and recognition of further disease events, also basicthings such as identifying innovative imaging features and establishing a novel measure of OA status. Future OA treatment discoveries may be aided by the continuous improvement of machine learning models.

3-dimensional bone shape and knee osteoarthritis: What have we learned?

The concept that multiple joint tissues are involved in the osteoarthritis (OA) disease process is now widely accepted. There have been significant and important insights over the past two decades in the understanding of bone as a tissue undergoing pathological changes in OA. The specific bony changes of osteophyte growth and “bone attrition” associated with OA have been recognized for many years with several semi-quantitative radiographic and magnetic resonance imaging (MRI) grading systems designed to capture the magnitude of these changes. Over the past decade, there has been significant and important progress in the quantitative measurement of these changes. Manual methods for measuring bone area from 3D MR images have been improved with automation which offers both superior precision and a more responsive measurement that has been applied in several DMOAD randomized controlled trials. Measurement of true 3D bone shape, as opposed to simple geometric measures such as curvature and length, depends on automated methods of segmentation. In this field, important developments have taken place in the statistical parameterization of shape and the construction of OA vs non-OA shape metrics. Work has demonstrated that bone shape may provide an indication of OA status, may predict future OA onset, and is associated with clinical markers of OA such as pain, function and total joint replacement (TKR). Thus, bone shape may be a useful imaging biomarker for OA.

Investigation of periodontitis, halitosis, xerostomia, and serological characteristics of patients with osteoarthritis and rheumatoid arthritis and identification of new biomarkers.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two different types of arthritis. Within RA, the subsets between seronegative RA (snRA) and seropositive RA (spRA) represent distinct disease entities; however, identifying clear distinguishing markers between them remains a challenge. This study investigated and compared the oral health conditions in patients with RA and OA to clarify the differences from healthy controls. In addition, we investigated the serological characteristics of the patients, the factors that distinguished patients with RA from those with OA, and the main factors that differentiated between snRA and spRA patients. A total of 161 participants (mean age: 52.52 ± 14.57years, 32 males and 129 females) were enrolled in this study and categorized as: normal (n = 33), OA (n = 31), and RA (n = 97). Patients with RA were divided into the following two subtypes: snRA (n = 18) and spRA (n = 79). Demographics, oral health, and serological characteristics of these patients were compared. The prevalence of periodontal diseases was significantly higher in patients with OA (100%) and RA (92.8%) than in healthy controls (0.0%). However, the presence of periodontal diseases was not utilized as a distinguishing factor between OA and RA. Xerostomia occurred more frequently in patients with RA (84.5%) than in patients with OA (3.2%) and healthy controls (0.0%) (all p < 0.001). ROC analysis revealed that periodontal disease was a very strong predictor in the diagnosis of OA compared to healthy controls, with an AUC value of 1.00 (p < 0.001). Additionally, halitosis (AUC = 0.746, 95% CI 0.621-0.871, p < 0.001) and female sex (AUC = 0.663, 95% CI 0.529-0.797, p < 0.05) were also significant predictors of OA. The strongest predictors of RA diagnosis compared to healthy controls were periodontal diseases (AUC = 0.964), followed by xerostomia (AUC = 0.923), age (AUC = 0.923), female sex (AUC = 0.660), and halitosis (AUC = 0.615) (all p < 0.05). Significant serological predictors of RA were anti-CCP Ab (AUC = 0.808), and RF (AUC = 0.746) (all p < 0.05). In multiple logistic regression analysis, xerostomia (odds ratio, OR: 8124.88, 95% CI 10.37-6368261.97, p-value = 0.008) and Anti-CCP Ab (OR: 671.33, 95% CI 2.18-207,074.02, p = 0.026) were significant predictors for RA compared to OA. When diagnosing spRA compared to snRA, anti-CCP Ab (AUC = 1.000, p < 0.001) and RF (AUC = 0.910, 95%CI 0.854-0.967, p < 0.001) had outstanding predictive performances. Therefore, clinicians and researchers should thoroughly evaluate the oral status of both OA and RA patients, alongside serological factors, and consider these elements as potential predictors.

Failure after operative repair is higher for ballistic femoral neck fractures than for closed, blunt-injury fractures: a multicenter retrospective cohort study

IntroductionThe purpose of this study was to describe the outcomes after operative repair of ballistic femoral neck fractures. To better highlight the devastating nature of these injuries, we compared a...

Persistent Early Knee Osteoarthritis Symptoms From 6 to 12 Months After Anterior Cruciate Ligament Reconstruction.

Early identification of knee osteoarthritis (OA) symptoms after anterior cruciate ligament reconstruction (ACLR) could enable timely interventions to improve long-term outcomes. However, little is known about the change in early OA symptoms from 6 to 12 months post-ACLR. To evaluate the change over time in meeting classification criteria for early knee OA symptoms from 6 to 12 months after ACLR. Prospective cohort study. Research laboratory. Eighty-two participants aged 13 to 35 years who underwent unilateral primary ACLR. On average, participants' first and second visits were 6.2 and 12.1 months post-ACLR. Early OA symptoms were classified using generic (Luyten Original) and patient population-specific (Luyten Patient Acceptable Symptom State [PASS]) thresholds on Knee injury and Osteoarthritis Outcome Score (KOOS) subscales. Changes in meeting early OA criteria were compared between an initial and follow-up visit at an average of 6 and 12 months post-ACLR, respectively. Twenty-two percent of participants exhibited persistent early OA symptoms across both visits using both the Luyten Original and PASS criteria. From initial to follow-up visit, 18% to 27% had resolution of early OA symptoms, while 4% to 9% developed incident symptoms. In total, 48% to 51% had no early OA symptoms at either visit. No differences were found for change in early OA status between adults and adolescents. Nearly one-quarter of participants exhibited persistent early knee OA symptoms based on KOOS thresholds from 6 to 12 months post-ACLR. Determining if this symptom persistence predicts worse long-term outcomes could inform the need for timely interventions after ACLR. Future researchers should examine if resolving persistent symptoms in this critical window improves later outcomes. Tracking early OA symptoms over time may identify high-risk patients who could benefit from early treatment.

Vitamin D, PTH, and Lipid Dysregulation in Osteoarthritis: A Case-Control Study.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, bone remodeling, and pain. Recent evidence suggests that Vitamin D insufficiency, alterations in parathyroid hormone (PTH) levels, and dyslipidemia may play roles in the pathophysiology of OA, affecting calcium homeostasis and bone health. We investigated the association between Vitamin D, PTH levels, lipid profile, and calcium homeostasis in OA patients. This case-control study involved 200 participants, divided into OA and control groups, at a tertiary care center from April to May 2023. Serum levels of 25-hydroxyvitamin D, PTH, total cholesterol, HDL, LDL, triglycerides, and calcium were measured. Statistical analysis was conducted to assess correlations between these biomarkers and OA status. OA patients demonstrated significantly lower Vitamin D levels and higher PTH and total cholesterol levels compared to controls. Vitamin D insufficiency was prevalent, with a notable correlation between decreased Vitamin D levels, elevated PTH, and dyslipidemia. These findings suggest a potential metabolic interplay affecting OA progression and symptomatology. The study highlights a significant association between Vitamin D insufficiency, altered PTH levels, and lipid dysregulation in OA patients, underscoring the importance of assessing these parameters in the clinical management of OA. Further research is needed to explore the therapeutic implications of correcting Vitamin D insufficiency and lipid abnormalities in OA.

Effects of low-level laser therapy on acupuncture points on knee pain and function in knee osteoarthritis.

Knee osteoarthritis is a common and disabling disease. We aimed to examine the effect of low-level laser therapy in addition to routine physical therapy modalities (transcutaneous electrical stimulation, superficial heating modality of infrared, ultrasound, and exercise) on the functional status and pain in knee osteoarthritis. Patients with knee osteoarthritis (n=71) who underwent physical therapy (transcutaneous electrical stimulation, infrared, ultrasound, exercise therapy, and low-level laser therapy) were retrospectively screened. Patients who received low-level laser therapy on acupuncture points, transcutaneous electrical stimulation, infrared, ultrasound, and exercise were included in the low-level laser therapy (+) (n=35), and patients who received only transcutaneous electrical stimulation, ultrasound, infrared, and exercise were included in the low-level laser therapy (-) group (n=36). The Visual Analog Scale for activity pain, Lysholm Knee Scoring Scale, and walking and stair climbing tests were used before and after treatment obtained from patient files. The post-treatment Visual Analog Scale activity score and walking and stair climbing test results were statistically significantly lower in the low-level laser therapy (+) group than in the low-level laser therapy (-) group. There was no significant difference in post-treatment Lysholm Knee Scoring Scale scores between the two groups. In both groups, the Visual Analog Scale activity, Lysholm Knee Scoring Scale, and walking and stair climbing test scores statistically significantly decreased after treatment. Knee osteoarthritis increases with aging and creates significant functional limitations. low-level laser therapy with routine physiotherapy contributed to the improvement in the pain and functional status of the patients with knee osteoarthritis. Low-level laser therapy can be recommended in osteoarthritis treatment guidelines with the support of further studies, which is an easy-to-apply, effective, and reliable method.

Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis: A Mendelian randomisation investigation

ObjectiveSpinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, osteoarthritis, and spinal stenosis using Mendelian randomization (MR) techniques. DesignWe applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between osteoarthritis and spinal stenosis with LD score regression and CAUSE MR method. Finally, we used multivariable MR to explore whether osteoarthritis and BMI mediate the causal pathways identified. ResultsOur analysis revealed strong evidence for the effect of higher BMI (OR=1.54, 95%CI:1.41-1.69, p-value=2.7 x 10-21), waist (OR=1.43, 95%CI:1.15-1.79, p-value=1.5x10-3) and hip (OR=1.50, 95%CI:1.27-1.78, p-value=3.3x10-6) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR=1.21, 95%CI:1.12-1.29, p-value=1.6x10-7), femoral neck (OR=1.35, 95%CI:1.09-1.37, p-value=7.5x10-7), and lumbar spine (OR=1.38, 95%CI:1.25-1.52, p-value=4.4x10-11). We detected high genetic correlations between spinal stenosis and osteoarthritis (rg range: 0.47-0.66), with CAUSE results supporting a causal effect of osteoarthritis on spinal stenosis (ORallOA=1.6, 95%CI:1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for osteoarthritis in the multivariable MR. ConclusionsGenetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of osteoarthritis status. These results may inform preventative strategies and treatments.

Elevated secretion of pro-collagen I-alpha and vascular endothelial growth factor as biomarkers of acetabular labrum degeneration and calcification in hip osteoarthritis: An explant study

BackgroundHip osteoarthritis (OA) involves structural degeneration of different joint compartments, including femoral head cartilage, periarticular ligaments and the acetabular labrum. However, the molecular mechanisms underlying labrum degeneration in hip OA remain poorly understood. AimTo assess secretion of putative biomarkers for OA from explanted human labrum tissues under basal and inflammatory conditions and to determine whether these could differentiate between OA and calcification status compared to fracture controls. MethodsIntact labrum specimens were collected from patients undergoing joint arthroplasty for primary hip OA (n ​= ​15, mean age 70) or non-OA femoral neck fracture (n ​= ​5, mean age 64). Tissues were dissected in equal-sized samples and explanted for one week. To mimic activation of inflammatory signaling by endogenous damage-associated molecular patterns (DAMP) tissue were stimulated with a toll-like receptor 4 (TLR4) agonist (1 ​μg/mL LPS). The involvement of transforming growth factor-beta (TGF-beta) signaling was evaluated by treatment with a TGF-beta type 1 receptor inhibitor (10 ​μM SB-505124). Secretion of aggrecan (ACAN), pro-collagen-I alpha (Pro-Col-Iα), cartilage oligomeric matrix protein (COMP), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) was assessed by enzyme-linked immunosorbent assay (ELISA). Labrum calcification was evaluated by 3D whole mount fluorescent microscopy of ethyl cinnamate-based optically cleared tissues stained with Alcian blue/Alizarin red. ResultsWhole mount microscopy revealed non-OA fracture controls were non-calcified, whereas six OA labra (40%) were partially calcified or ossified. Basal secretion of Pro-Col-Iα and VEGF was increased four-fold in OA versus non-OA labra. Pro-Col-Iα levels were correlated with those of VEGF (r ​= ​0.65) and COMP (r ​= ​0.54). Stimulation of DAMP signaling through TLR4 affected secretion of IL-6, VEGF, COMP and Pro-Col-Iα, with distinct responses between non-OA and OA tissues. Inhibition of TGF-beta signaling specifically reduced elevated secretion of Pro-Col- Iα and VEGF in calcified OA labrum. ConclusionsSecretion of the putative OA biomarkers Pro-Col-Iα and VEGF is elevated in degenerated human acetabular labrum and may serve as indicators of OA and calcification status. Secretion of both factors was partially regulated by TGF-beta signaling in calcified OA labrum tissues.The Translational potential of this article:Our findings suggest that a biomarker panel consisting of Pro-Col-Iα/VEGF/COMP may be valuable for assessing subradiographic labrum degeneration and calcification in hip OA. Targeting TGF-beta signaling may offer a means to reduce vascular invasion and fibrosis in acetabular labrum tissue.

The Complex Interplay between the Gut Microbiome and Osteoarthritis: A Systematic Review on Potential Correlations and Therapeutic Approaches.

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE's risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients.

Neuromuscular Responses and Perceptions of Health Status and Pain-Related Constructs in End-Stage Knee Osteoarthritis During Resistance Training With Blood Flow Restriction.

Ogrezeanu, DC, López-Bueno, L, Sanchís-Sánchez, E, Carrasco, JJ, Cuenca-Martínez, F, Suso-Martí, L, López-Bueno, R, Cruz-Montecinos, C, Martinez-Valdes, E, Casaña, J, and Calatayud, J. Neuromuscular responses and perceptions of health status and pain-related constructs in end-stage knee osteoarthritis during resistance training with blood flow restriction. J Strength Cond Res 38(4): 762-772, 2024-We aimed to evaluate the neuromuscular responses and their relationship with health status, kinesiophobia, pain catastrophizing, and chronic pain self-efficacy in patients with end-stage knee osteoarthritis during acute resistance training with different levels of blood flow restriction (BFR). Seventeen patients with end-stage knee osteoarthritis participated in 3 experimental sessions separated by 3 days, performing 4 sets of knee extensions with low load and 3 levels of concurrent BFR performed in a random order: control (no BFR), BFR at 40% arterial occlusion pressure (AOP), and BFR at 80% AOP. Normalized root-mean-square (nRMS), nRMS spatial distribution (centroid displacement, modified entropy, and coefficient of variation), and normalized median frequency (nFmed) were calculated from the vastus medialis (VM) and lateralis (VL) using high-density surface electromyography. Subjects were asked to report adverse effects after the sessions. In the VM, nRMS was higher with 80% AOP than with 40% AOP ( p = 0.008) and control ( p < 0.001), whereas there were no differences between conditions in the VL. Normalized root-mean-square also showed an association with pain catastrophizing, chronic pain self-efficacy, and health status (VM: -0.50, 0.49, -0.42; VL: -0.39, 0.27, -0.33). Spatial distribution varied between conditions but mostly in the VL. Overall, nFmed did not vary, with only a slight increase in the VL with 40% AOP, between set 3 and 4. BFR during knee extensions at 80% AOP increases VM activity and VL amplitude distribution more than 40% AOP and control. Importantly, muscle activity increases are modulated by pain catastrophizing, chronic pain self-efficacy, and health status in these patients, and kinesiophobia seems to especially modulate entropy.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

To assess whetherchanges in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45-79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: - 1.85 N/year, - 3.23 to - 0.47) and specific contractile force (- 0.04 N/cm2/year, - 0.07 to - 0.01),decreased thigh muscle contractile percent (- 0.03%/year, - 0.06 to - 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care.