Therapeutic Advances in Musculoskeletal Disease最新文献

Background: Osteoarthritis (OA) is associated with lost range of motion in the affected joint(s). Evidence suggests that this may be due to increased activity of posterior capsule fibroblasts, cells in turn derived from mesenchymal stromal cells (MSCs).

Objectives: To test the hypotheses that (1) MSCs are more numerous in the posterior capsule of patients with knee flexion contracture (FC) and (2) in OA participants with knee FC, the MSC population in the posterior capsule differentiates toward a fibrotic phenotype. In order to complete these objectives, we looked for associations between capsule histologic and MSC outcomes with clinical outcomes.

Design: Cross-sectional translational research design using data from the Ottawa Knee Osteoarthritis (OKOA) database.

Methods: A total of 71 OKOA database participants and their relevant clinical and laboratory outcomes were included. Associations were first tested with bivariate correlation, then for p < 0.10, tested using a linear model.

Results: No lab-based differences between FC and no-FC groups we discovered. In the posterior capsule, there was an association between knee flexion and adipogenic capacity (p = 0.001), osteogenic capacity (p < 0.001), KL grade and percent "other" (mainly neurovascular) tissue (p = 0.039), visual analog scale pain, and percent fibrous tissue (p = 0.014). For the anterior capsule, there was an association between knee flexion (p = 0.002) and extension (p = 0.005) with MSC enumeration, KL grade with MSC fibrogenic capacity (p = 0.002), and Knee Injury and Osteoarthritis Outcome Score quality of life with chondrogenic capacity (p < 0.001).

Conclusion: Joint capsule composition, MSC enumeration, and function were associated with important clinical OA outcomes. These findings suggest that the entire joint capsule may play an important role in OA-related morbidity and progression and could represent an underappreciated target for OA treatment.

Background: Although extramusculoskeletal manifestations, such as uveitis and psoriasis, in patients with axial spondyloarthritis (SpA) are well-documented, studies on the occurrence of glomerulonephritis in this population are scarce.

Objectives: This study aimed to assess the incidence rate and risk factors for glomerulonephritis in patients with axial SpA using a nationwide population-based cohort in Korea.

Design: Nationwide population-based study.

Methods: This study included patients diagnosed with axial SpA between 2016 and 2019 from Korea's National Health Insurance Database. Patients with a diagnosis of preexisting kidney disease prior to their axial SpA diagnosis and those diagnosed with glomerulonephritis within 1 year of their axial SpA diagnosis were excluded. For the remaining patients, the incidence rates of glomerulonephritis and Cox proportional hazard ratios were analyzed.

Results: Among the 11,796 patients, 58 had glomerulonephritis, resulting in an incidence rate of 1.82 per 1000 person-years. After adjusting for age and sex, the hazard ratio for patients with a Charlson Comorbidity Index score of ⩾1 was 2.03 (confidence interval (CI), 1.14-3.63; p = 0.017). When adjusting for age, sex, and comorbidities, the hazard ratio for patients with hypertension was 2.37 (CI, 1.20-4.69; p = 0.014). Among the 58 patients, 4 (6.9%) were diagnosed with glomerulonephritis, as confirmed via kidney biopsy.

Conclusion: The incidence rate of glomerulonephritis in Korean patients with axial SpA is lower than that in patients with other musculoskeletal manifestations. In addition, the presence of comorbidities, including hypertension, is a significant risk factor for glomerulonephritis in patients with axial SpA. Despite the low occurrence, careful monitoring for glomerulonephritis in patients with axial SpA is essential.

Gout and calcium pyrophosphate deposition (CPPD) disease are the most common causes of crystal arthritis. Identifying the pathogenic crystal deposition is the cornerstone of the diagnosis, but also prognosis and monitoring of the diseases. Conventional radiography has been for decades the only imaging technique used, with its very restricted sensitivity in both diseases. Advanced techniques, namely ultrasound and dual-energy computed tomography (DECT), are being increasingly used in the diagnosis and management of gout and CPPD diseases, and their role is now well recognized in classification criteria and in recommendations for the diagnosis and management. In gout, ultrasound elementary lesions of monosodium urate deposition are well defined and have been shown to be sensitive to change and can be monitored, while direct quantification of these deposits can be performed with DECT. In CPPD disease, the definition of elementary lesions and their scoring has been well established for ultrasound, while the proof of concept that DECT can help discriminate calcium pyrophosphate crystal deposits among other calcium-containing structures has been shown. The aim of this narrative review is to provide an overview of the use of advanced imaging techniques in crystal-induced arthropathies.

Background: Randomized clinical trials have demonstrated the efficacy of secukinumab (SECU) in reducing disease activity in psoriatic arthritis (PsA), while real-world studies prove a broader perspective on SECU's usefulness in everyday clinical practice.

Objectives: To assess the effectiveness of SECU by evaluating drug survival and identifying potential predictors of clinical response and treatment discontinuation in patients with moderate-to-severe PsA, using real-world data from the Italian Group for the Study of Early Arthritis (GISEA) registry.

Design: This longitudinal retrospective study included PsA patients treated with SECU, spanning from May 2016 to November 2023.

Methods: Data from 1045 PsA patients, including 783 with peripheral-only PsA (perPsA) and 262 with peripheral and axial involvement (mixed PsA) were analyzed. Drug survival was estimated by Kaplan-Meier analysis. Clinical outcomes, including Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriasis Area Severity Index (PASI), Ankylosing Spondylitis Disease Activity Score (ASDAS, C-Reactive Protein (CRP)-based), and Visual Analogue Scale (VAS) measures, were evaluated at baseline and at 6, 12, and 24 months. Adjusted hazard ratios (aHRs) for discontinuing SECU were determined using multivariate Cox regression models.

Results: SECU survival at 24 months was 63.24%, significantly higher in mixed PsA compared to perPsA (p = 0.036). In the overall PsA population, DAPSA scores decreased significantly at 6 months, and further at 24 months (all p < 0.0001). In mixed PsA, ASDAS-CRP scores were significantly reduced at 6 months and remained stable through 24 months (all p < 0.0001). VAS pain scores also improved already at 6 months and continued to improve at 24 months (all p < 0.0001). Higher age (aHR = 0.98, 95% confidence interval (CI): 0.96-0.99, p = 0.007) and lower baseline DAPSA scores (aHR = 1.02, 95% CI: 1.01-1.03, p = 0.014) were associated with greater persistence of SECU treatment. SECU was well tolerated, with no serious adverse events.

Conclusion: SECU showed sustained clinical improvements in both peripheral and axial involvement of PsA patients over 24 months, with higher persistence observed in mixed PsA patients. Our findings highlight the favorable clinical and safety profile of SECU in real world.

Background: Anti-signal recognition particle immune-mediated necrotizing myopathy (anti-SRP IMNM) is a rare autoimmune disorder characterized by muscle weakness and necrosis. Identifying clinical subgroups within this patient population could facilitate the management of the disease.

Objectives: To identify distinct clinical subgroups of anti-SRP IMNM patients.

Design: A retrospective study was conducted on anti-SRP IMNM patients treated at West China Hospital of Sichuan University between January 2010 and October 2023.

Methods: Clinical data were collected. Unsupervised cluster analysis was conducted to classify patients into distinct subgroups based on their clinical features. Statistical analyses were performed to compare the clinical characteristics and outcomes among the identified clusters.

Results: A total of 116 patients were included in the study, and 3 distinct clinical subgroups were identified: Cluster 3 (acute), Cluster 2 (subacute), and Cluster 1 (poor prognosis). Patients in Cluster 3 exhibited a short disease course (median 3 months), severe muscle weakness (78.38% with Medical Research Council (MRC) score ⩽3), high muscle enzyme levels, and a good response to treatment. Cluster 2 patients were younger (mean age 45.83 years), had a longer disease course (median 6.5 months), milder muscle damage, and lower autoantibody titers. Cluster 1 patients were older (mean age 58.10 years), predominantly male (70.97%), and had higher incidences of interstitial lung disease (70.97%) and cardiac injury (45.16%). In Cluster 1, 16.13% of cases were refractory, and the relapse rate was 38.71%, which was significantly higher compared to the other two clusters.

Conclusion: This study highlights the clinical heterogeneity among anti-SRP IMNM patients and identifies three distinct clinical subgroups with unique characteristics. These findings provide insights for personalized management.

Background: Rheumatoid arthritis (RA) and prolonged high-dose glucocorticoid (GC) treatment are established risk factors for osteoporosis.

Objectives: In this study, we aimed to evaluate the therapeutic efficacy of denosumab according to the GC dose considered to increase the risk of glucocorticoid-induced osteoporosis (GIOP) in patients with RA.

Design: A retrospective analysis of collected data on RA patients with osteoporosis starting denosumab.

Methods: We included 418 patients with RA who were started on denosumab therapy and categorized them into those with and without GC intake ⩾2.5 mg/day for >3 months. The T-score and areal bone mineral density (aBMD) at the lumbar spine, total hip, and femur neck, as well as serum bone turnover markers, were measured at baseline and 12 months. We performed between-group and within-group comparisons of the BMD values at baseline and at 12 months.

Results: Denosumab significantly increased the T-scores and aBMD at the lumbar spine, total hip, and femur neck after 12 months, regardless of GC intake. However, apart from the T-score at the lumbar spine, the other parameters did not show significant between-group differences. Similarly, in patients with anti-cyclic citrullinated peptide (CCP) antibody positivity or those treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), although there were significant increases in the T-score and areal BMD at all sites in both groups, there were no significant between-group differences.

Conclusion: Our findings suggest that the GC dose considered to increase the risk of GIOP did not significantly attenuate the therapeutic efficacy of denosumab in RA patients, including those positive for anti-CCP antibodies and users of biologic or targeted synthetic DMARDs.

Background: Previous meta-analyses have demonstrated osteoarthritis (OA) is associated with an increased risk of dementia, but these studies were prone to bias based on residual confounding factors and reverse causality.

Objectives: We aimed to investigate associations between OA and cognitive function using data from the National Health and Nutrition Examination Survey (NHANES) and to investigate the causality using Mendelian randomization (MR).

Design: This is a cross-sectional study and MR study.

Methods: Data from the NHANES 2011-2014 were used. Multiple linear, logistic regressions and stratified analyses were used to determine the association between OA status and cognitive function. Sample weights were used to ensure result generalizability. Two-sample MR analysis was conducted to examine the association between OA and dementia. Mediation analyses were performed to investigate the mediating effects of depression.

Results: We did not demonstrate a significant association between OA and cognitive performance after adjusting for relevant covariates (p > 0.05), and the population of individuals with both OA and depression was associated with higher odds of low total word recall cognitive performance (odds ratio (OR) = 4.74, 95% confidence interval (CI): 1.09-20.63; p = 0.04). Genetically predicted specific-site OA was not significantly associated with the risk of dementia (OR = 1.12; 95% CI: 0.96-1.32; p = 0.16), Alzheimer's disease (OR = 0.95, 95% CI: 0.68-1.31, p = 0.74), vascular dementia (OR = 1.32, 95% CI: 0.82-2.13, p = 0.25) with accepted heterogeneity and no evidence of directional pleiotropy. Furthermore, major depression was found to mediate the pathway between OA and vascular dementia (β = 0.044, 95% CI: -0.391 to 0.479, p < 0.05).

Conclusion: Our findings indicate that there is no significant association or causal relationship between OA and cognitive decline. However, depression may serve as an important factor influencing cognitive outcomes. Future research should further explore the bidirectional causal relationship and underlying mechanisms.

Psoriatic arthritis (PsA) presents various clinical manifestations, including skin lesions, peripheral arthritis, axial involvement, enthesitis, nail involvement, dactylitis, and uveitis. In addition, it causes a high incidence of lifestyle-related diseases and an increase in cerebrovascular and cardiovascular events. As the pathology of PsA has been clarified, molecular-targeted drugs targeting tumor necrosis factor-α, interleukin (IL)-17A, IL-17A/F, IL-17 receptor, IL-12/23(p40), IL-23p19, Cytotoxic T-lymphocyte Antigen-4 (CTLA-4), Janus kinase, and phosphodiesterase-4 have been developed and are widely used in clinical practice. PsA is clinically and molecularly heterogeneous, and it is necessary to improve various clinical symptoms with limited treatment options simultaneously; therefore, rheumatologists sometimes encounter difficult situations in clinical practice. Hence, the development of precision medicine may improve treatment outcomes. Recently, the strategic use of molecular-targeted drugs based on the stratification of patients with PsA by peripheral blood lymphocyte phenotyping and serum cytokine concentrations has been reported to possibly lead to a higher therapeutic response. A randomized controlled trial was initiated to verify the efficacy of this treatment strategy. However, to make precision medicine in PsA feasible, shifting from conventional clinical trials to clinical trials based on biomarker profiles and accumulating further data are necessary.

Background: Rheumatology has experienced notable changes in the last decades. New drugs, including biologic agents and Janus kinase (JAK) inhibitors, have blossomed. Concepts such as window of opportunity, arthralgia suspicious for progression, or difficult-to-treat rheumatoid arthritis (RA) have appeared; and new management approaches and strategies such as treat-to-target have become popular. Statistical learning methods, gene therapy, telemedicine, or precision medicine are other advancements that have gained relevance in the field. To better characterize the research landscape and advances in rheumatology, automatic and efficient approaches based on natural language processing (NLP) should be used.

Objectives: The objective of this study is to use topic modeling (TM) techniques to uncover key topics and trends in rheumatology research conducted in the last 23 years.

Design: Retrospective study.

Methods: This study analyzed 96,004 abstracts published between 2000 and December 31, 2023, drawn from 34 specialized rheumatology journals obtained from PubMed. BERTopic, a novel TM approach that considers semantic relationships among words and their context, was used to uncover topics. Up to 30 different models were trained. Based on the number of topics, outliers, and topic coherence score, two of them were finally selected, and the topics were manually labeled by two rheumatologists. Word clouds and hierarchical clustering visualizations were computed. Finally, hot and cold trends were identified using linear regression models.

Results: Abstracts were classified into 45 and 47 topics. The most frequent topics were RA, systemic lupus erythematosus, and osteoarthritis. Expected topics such as COVID-19 or JAK inhibitors were identified after conducting dynamic TM. Topics such as spinal surgery or bone fractures have gained relevance in recent years; however, antiphospholipid syndrome or septic arthritis have lost momentum.

Conclusion: Our study utilized advanced NLP techniques to analyze the rheumatology research landscape and identify key themes and emerging trends. The results highlight the dynamic and varied nature of rheumatology research, illustrating how interest in certain topics has shifted over time.

Background: Recent studies have shown the impact of obesity on achieving low disease activity or remission in rheumatoid arthritis (RA) patients treated with tumor necrosis factor inhibitors. However, there is limited research on the effects of obesity on clinical responses to non-TNF-targeted treatments.

Objectives: This study investigated the influence of body mass index (BMI) on clinical response to non-TNF-targeted treatments in RA patients.

Design: We used data from the KOrean nationwide BIOlogics & targeted therapy (KOBIO) registry, a multicenter, prospective, observational cohort that included RA patients in South Korea.

Methods: Patients who received at least one prescription for non-TNF-targeted treatments, including abatacept, tocilizumab, and Janus kinase inhibitors, were included. They were categorized into three BMI groups: under 25 kg/m² (434 patients), between 25 and 30 kg/m² (146 patients), and over 30 kg/m² (22 patients). After 1 year of treatment, treatment continuation rates and clinical responses among these BMI groups were compared. Time on treatment for each category was analyzed using Kaplan-Meier curves and Cox regression, adjusting for confounders.

Results: The 1-year continuation rate of the targeted treatment was significantly lower in the obese group (81.8%) compared to the normal BMI (93.8%) and overweight (89.0%) groups (p = 0.033). Disease Activity Score of 28 joints-erythrocyte sedimentation rate score improvement was less in the obese group (2.06 ± 2.14) than in the normal BMI group (2.76 ± 1.55) (p = 0.045). Multivariable Cox proportional hazard analysis showed a higher discontinuation rate in the obese group (hazard ratio: 3.407, 95% confidence interval: 1.157-10.211; p = 0.029).

Conclusion: Higher BMI in RA patients was associated with poorer clinical response and higher discontinuation rates for non-TNF-targeted treatments.