Osteoarthritis and cartilage open最新文献

Objective

Obesity is a leading risk factor for both the incidence and progression of osteoarthritis (OA). Omic technologies, including transcriptomics and metabolomics are capable of identifying RNA and metabolite profiles in tissues and biofluids of OA patients. The objective of this review is to highlight studies using transcriptomics and metabolomics that contribute to our understanding of OA pathology in relation to obesity.

Design

We conducted a targeted search of PUBMED for articles, and GEO for datasets, published up to February 13, 2024, screening for those using high-throughput transcriptomic and metabolomic techniques to study human or pre-clinical animal model tissues or biofluids related to obesity-associated OA. We describe relevant studies and discuss challenges studying obesity as a disease-related factor in OA.

Results

Of the 107 publications identified by our search criteria, only 15 specifically used transcriptomics or metabolomics to study joint tissues or biofluids in obesity-related OA. Specific transcriptomic and metabolomic signatures associated with obesity-related OA have been defined in select local joint tissues, biofluids and other biological material. However, considerable challenges exist in understanding contributions of obesity-associated modifications of transcriptomes and metabolomes related to OA, including sociodemographic, anthropometric, dietary and molecular redundancy-related factors.

Conclusions

A number of additional transcriptomic and metabolomic studies are needed to comprehensively understand how obesity affects OA incidence, progression and outcomes. Integration of transcriptome and metabolome signatures from multiple tissues and biofluids, using network-based approaches will likely help to better define putative therapeutic targets that could enable precision medicine approaches to obese OA patients.

Objective

The aim of this study was to compare the magnitude and the predictors of the placebo response in an internet versus onsite randomised controlled trials (RCTs) in people with hand osteoarthritis (HOA).

Method

This study is a post-hoc analysis based on one internet RCT (RADIANT) and previously published onsite RCTs for HOA identified through a rigorous searching and selection strategy. The magnitude of the placebo response in the two different types of RCTs were compared using heterogeneity statistics and forest plots visualisation. Classic placebo predictors as well as a combined model, defined with data from onsite RCTs, were tested to predict the placebo response.

Results

We analysed the dataset from RADIANT and fourteen previously published onsite RCTs. None of the analyses showed a significant difference between the placebo response for the internet versus onsite RCTs. The “classic” placebo predictors combined in a multivariate predictive model correlated significantly with the placebo response measured in RADIANT study.

Conclusion

Despite the absence of face-to-face interactions with the study personnel, there is no evidence that either the magnitude or the predictors of the placebo response of this internet RCT differ from those of onsite RCTs. This analysis is considered as a first step towards evaluating the difference between these designs and strengthens the argument that internet RCTs remain an acceptable alternative way to assess the efficacy of an active treatment in comparison to a placebo.

The aim of this narrative review is to synthesize the available data describing the efficacy and safety of medications approved for obesity management and to provide an overview of upcoming agents in development.

A literature search of PubMed, Medline, and Embase databases identified relevant articles describing medications approved in the U.S., Australia, U.K., and/or Europe. Papers were selected based on relevance and originality, with phase 3 clinical trials and meta-analyses preferentially included.

Six medications are widely approved for long-term weight management in conjunction with lifestyle interventions in people with body mass index (BMI) ≥30 ​kg/m² or BMI ≥27 ​kg/m² and at least one medical condition related to excess weight. Compared with lifestyle interventions alone, all medications approved for obesity management are more effective for long-term weight loss and improvements in cardiometabolic risk factors. Older obesity medications are associated with mean weight losses in the range of 5–10%. The new generation of agents, including the injectable incretin analogues semaglutide and tirzepatide are associated with sustained mean weight reductions of 15–20%, along with substantial benefits on a range of health outcomes. Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years.

As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Other important challenges for clinical practice and research include the need for long-term strategies to prevent and manage weight regain and loss of lean muscle and bone mineral density.

Objective

To evaluate adiposity after anterior cruciate ligament reconstruction (ACLR): i) cross-sectionally (1-year post-ACLR) compared to uninjured controls; ii) longitudinally up to 5 years post-ACLR; and iii) associations with patient-reported symptoms and physical performance.

Methods

In 107 individuals post-ACLR and 19 controls, we assessed global (BMI), peripheral (subcutaneous adipose tissue thickness on the posteromedial side of knee MRI), and central (waist circumference in ACLR group) adiposity. Patient-reported symptoms (Knee injury and Osteoarthritis Outcome Score) and physical performance (hop for distance) were evaluated at 1 and 5 years post-ACLR. Linear regression models evaluated adiposity between groups. Paired t-tests evaluated changes in adiposity from 1- to 5 years post-ACLR. Linear regression models analyzed adiposity's associations with patient-reported symptoms and physical performance at 1-year post-ACLR, changes in symptoms and performance over 4 years post-ACLR, and longitudinal changes in adiposity and symptoms and performance, controlling for age, sex, and activity level.

Results

Individuals 1-year post-ACLR were associated with higher average global (3 ​kg/m²) and peripheral adiposity (2.3 ​mm). From 1- to 5 years post-ACLR, higher average global (0.58 ​kg/m²) and central (5 ​cm) adiposity, and lower average peripheral adiposity (1.3 ​mm) were observed. In general, adiposity at one-year post-ACLR was negatively associated with patient-reported symptoms and physical performance, and changes from 1 to 5 years post-ACLR. Increases in adiposity were negatively associated with changes in patient-reported symptoms and physical performance over four years post-ACLR.

Conclusion

Greater global and central adiposity is a feature of young adults following ACLR and influences current and future patient-reported symptoms and physical performance.

Objective

Visual narratives have been used in medicine to share information in the form of stories with the potential to improve understanding of conditions and change behaviours. One genre of visual narratives is “graphic medicine”, which integrates comics into medical education and the delivery of healthcare. Graphic medicine can maximise the impact of research findings by presenting them in a more accessible format, which may be particularly useful in certain populations, such as those with low levels of health literacy. Those with lower health literacy levels and osteoarthritis (OA) are less likely to manage their condition with guideline recommended management strategies, experience a higher burden of disease, and have lower access to care. Our objectives were to review the current visual narratives in the field of and create a graphic medicine visual narrative based on existing research.

Design

This paper summarises the current visual narratives in OA and presents a graphic medicine visual narrative to illustrate the experience of living with OA. Considerations for the dissemination of visual narratives to target audiences are also discussed.

Results

The most common visual narratives in are infographics, videos, and graphic medicine. A graphic medicine visual narrative, based on previous qualitative work and informed by a framework, was created to illustrate two distinct narratives – impairment and participatory.

Conclusion

Visual narratives remain an emerging field in OA but may serve as a useful resource for patients or clinicians to discuss various aspects of OA management. Future research should evaluate and validate the use of visual narratives in OA.

Objective

To investigate associations between obesity-linked systemic factors and gene expression indicative for the inflammatory and fibrotic processes in the infrapatellar fat pad (IFP), in a population of obese patients with end-stage knee osteoarthritis (KOA).

Methods

We collected human IFPs from 48 patients with a mean body mass index (BMI) of 35.44 ​kg/m² during total knee replacement procedures. These patients were part of a randomized controlled trial and met the criteria of having OA and a BMI of ≥30 ​kg/m². Blood samples were collected to assess serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and leptin. Total body composition was measured using dual-energy X-ray absorptiometry. Gene expressions of IL6, TNFA, COL1A1, IL1B, ASMA, PLOD2 in the IFP were analyzed.

Results

Univariate analysis resulted in a positive correlation between BMI and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression (r² ​= ​0.13). In univariate analyses of obesity-linked systemic factors and PLOD2, significant correlations were found for lean mass (r² ​= ​0.20), fat mass (r² ​= ​0.20), serum cholesterol (r² ​= ​0.17), serum triglycerides (r² ​= ​0.19) and serum leptin (r² ​= ​0.10). A multiple linear regression model indicated fat mass to be a strong predictor of PLOD2 production in the IFP (r² ​= ​0.22, P ​= ​0.003).

Conclusion

Our study demonstrates the positive association between fat mass and PLOD2 expression in the IFP of obese end-stage knee OA patients. This may indicate that within this patient population the fibrotic process in the IFP is influenced by systemic adipose tissue, next to local inflammatory processes.

Objective

To examine changes in prevalence and socioeconomic inequalities in knee and hip OA outcomes, in more specific surgery and non-surgery specialist care visits, from 2001 to 2011 in Sweden and to what extent sociodemographic factors can explain the changes.

Design

We included all individuals aged ≥35 years resident in Sweden from 2001 to 2011. Individual-level data was retrieved from the Swedish Interdisciplinary Panel. Highest educational attainment was used as socioeconomic measure and the concentration index was used to assess relative and absolute educational inequalities. We used decomposition method to examine changes in prevalence and relative educational inequalities.

Results

A total of 4,794,693 and 5,359,186 people were included for the years 2001 and 2011, respectively. The crude prevalence of surgery and specialist visits for knee and hip OA was 36–83% higher in 2011 than in 2001. The increase in hip OA outcomes was largely explained by changes in the sociodemographic composition of the population, whereas for knee OA outcomes, changes in the strength of the associations with sociodemographic factors appeared more important. All outcomes were concentrated among people with lower education in all study years. The relative inequalities declined over the study period, while the absolute inequalities increased for knee OA outcomes and remained stable for hip OA.

Conclusion

Our findings show an increasing burden of all studied OA outcomes. Moreover, our findings suggest persistent educational inequalities with more surgeries and specialist visits among lower-educated individuals. Future research should incorporate additional variables to better understand and address these inequalities.

Objective

We aimed to create an imaging biomarker for knee shape using knee dual-energy x-ray absorptiometry (DXA) scans and investigate its potential association with subsequent total knee replacement (TKR), independently of radiographic features of knee osteoarthritis and established risk factors.

Methods

Using a 129-point statistical shape model, knee shape (expressed as a B-score) and minimum joint space width (mJSW) of the medial joint compartment (binarized as above or below the first quartile) were derived. Osteophytes were manually graded in a subset of images and an overall score was assigned. Cox proportional hazards models were used to examine the associations of B-score, mJSW and osteophyte score with TKR risk, adjusting for age, sex, height and weight.

Results

The analysis included 37,843 individuals (mean age 63.7 years). In adjusted models, B-score was associated with TKR: each unit increase in B-score, reflecting one standard deviation from the mean healthy shape, corresponded to a hazard ratio (HR) of 2.25 (2.08, 2.43), while a lower mJSW had a HR of 2.28 (1.88, 2.77). Among the 6719 images scored for osteophytes, mJSW was replaced by osteophyte score in the most strongly predictive model for TKR. In ROC analyses, a model combining B-score, osteophyte score, and demographics outperformed a model including demographics alone (AUC ​= ​0.87 vs 0.73).

Conclusions

Using statistical shape modelling, we derived a DXA-based imaging biomarker for knee shape that was associated with kOA progression. When combined with osteophytes and demographic data, this biomarker may help identify individuals at high risk of TKR, facilitating targeted interventions.

Objective

Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model.

Methods

Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n ​= ​9) or sham VGX (non-VGX, n ​= ​6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint.

Results

At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p ​= ​0.055; stance time imbalance ​= ​1.6 ​± ​1.6%) and shifted foot strike locations (p ​< ​0.001; spatial symmetry ​= ​48.4 ​± ​0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 ​± ​7.70 compared to the non-VGX animal sensitivity of 29.74 ​± ​9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p ​= ​0.076; VGX: 0.80 ​± ​0.036 ​mm²; non-VGX: 0.736 ​± ​0.066 ​mm²). No group differences in systemic inflammation were observed at endpoint.

Conclusions

VGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.

Objective

A prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets.

Methods

In vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2–0.5 ​MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data.

Results

Amide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 ​MPa seem to provide the best sparse IR spectra for cylindrical (d ​= ​3 ​mm) probe tips.

Conclusion

Laser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.