Thigh muscle composition changes in knee osteoarthritis patients during weight loss: Sex-specific analysis using data from osteoarthritis initiative.

OBJECTIVES: Sex of patients with knee osteoarthritis (KOA) may impact changes in thigh muscle composition during weight loss, the most well-known disease-modifying intervention. We investigated longitudinal sex-based changes in thigh muscle quality during weight loss in participants with KOA. METHODS: Using Osteoarthritis Initiative (OAI) cohort data, we included females and males with baseline radiographic KOA who experienced > 5 % reduction in Body Mass Index (BMI) over four years. Using a previously validated deep-learning algorithm, we measured Magnetic Resonance Imaging (MRI)-derived biomarkers of thigh muscles at baseline and year-4. Outcomes were the intra- and inter-muscular adipose tissue (Intra-MAT and Inter-MAT) and contractile percentage of thigh muscles between females and males. The analysis adjusted for potential confounders, such as demographics, risk factors, BMI change, physical activity, diet, and KOA status. RESULTS: A retrospective selection of available thigh MRIs from KOA participants who also had a 4-year weight loss (>5 % of BMI) yielded a sample comprising 313 thighs (192 females and 121 males). Female and male participants exhibited a comparable degree of weight loss (females: -9.72 ±â€¯4.38, males: -8.83 ±â€¯3.64, P-value=0.060). However, the changes in thigh muscle quality were less beneficial for females compared to males, as shown by a less degree of longitudinal decrease in Intra-MAT (change difference,95 %CI: 783.44 mm2/4-year, 505.70 to 1061.19, P-value<0.001) and longitudinal increase in contractile percentage (change difference,95 %CI: -3.9 %/4-year, -6.5 to -1.4, P-value=0.019). CONCLUSIONS: In participants with KOA and 4-year weight loss, the longitudinal changes in thigh muscle quality were overall beneficial but to a less degree in females compared to males. Further research is warranted to investigate the underlying mechanisms and develop sex-specific interventions to optimize muscle quality during weight loss.

Comparison of 3T and 7T magnetic resonance imaging for direct visualization of finger flexor pulley rupture: an ex-vivo study.

OBJECTIVE: To compare image quality and diagnostic performance of 3T and 7T magnetic resonance imaging (MRI) for direct depiction of finger flexor pulleys A2, A3 and A4 before and after artificial pulley rupture in an ex-vivo model using anatomic preparation as reference. MATERIALS AND METHODS: 30 fingers from 10 human cadavers were examined at 3T and 7T before and after being subjected to iatrogenic pulley rupture. MRI protocols were comparable in duration, both lasting less than 22 min. Two experienced radiologists evaluated the MRIs. Image quality was graded according to a 4-point Likert scale. Anatomic preparation was used as gold standard. RESULTS: In comparison, 7T versus 3T had a sensitivity and specificity for the detection of A2, A3 and A4 pulley lesions with 100% vs. 95%, respectively 98% vs. 100%. In the assessment of A3 pulley lesions sensitivity of 7T was superior to 3T MRI (100% vs. 83%), whereas specificity was lower (95% vs. 100%). Image quality assessed before and after iatrogenic rupture was comparable with 2.74 for 7T and 2.61 for 3T. Visualization of the A3 finger flexor pulley before rupture creation was significantly better for 7 T (p < 0.001). Interobserver variability showed substantial agreement at 3T (κ = 0.80) and almost perfect agreement at 7T (κ = 0.90). CONCLUSION: MRI at 3T allows a comparable diagnostic performance to 7T for direct visualization and characterization of finger flexor pulleys before and after rupture, with superiority of 7T MRI in the visualization of the normal A3 pulley.

Approaches to optimize analyses of multidimensional ordinal MRI data in osteoarthritis research: A perspective.

Objective: Knee osteoarthritis (OA) is a disease of the whole joint involving multiple tissue types. MRI-based semi-quantitative (SQ) scoring of knee OA is a method to perform multi-tissue joint assessment and has been shown to be a valid and reliable way to measure structural multi-tissue involvement and progression of the disease. While recent work has described how SQ scoring may be used for clinical trial enrichment and disease phenotyping in OA, less guidance is available for how these parameters may be used to assess study outcomes. Design: Here we present recommendations for summarizing disease progression within specific tissue types. We illustrate how various methods may be used to quantify longitudinal change using SQ scoring and review examples from the literature. Results: Approaches to quantify longitudinal change across subregions include the count of number of subregions, delta-subregion, delta-sum, and maximum grade changes. Careful attention should be paid to features that may fluctuate, such as bone marrow lesions, or with certain interventions, for example pharmacologic interventions with anticipated cartilage anabolic effects. The statistical approach must align with the nature of the outcome. Conclusions: SQ scoring presents a way to understand disease progression across the whole joint. As OA is increasingly recognized as a heterogeneous disease with different phenotypes a better understanding of longitudinal progression across tissue types may present an opportunity to match study outcome to patient phenotype or to treatment mechanism of action.

Toward designing human intervention studies to prevent osteoarthritis after knee injury: A report from an interdisciplinary OARSI 2023 workshop.

Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.

Intra-Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study.

OBJECTIVE: Intra-articular (IA) mineralization may contribute to osteoarthritis (OA) structural progression. We studied the association of IA mineralization on knee computed tomography (CT) with cartilage damage worsening on knee magnetic resonance imaging (MRI), with a focus on location- and tissue-specific effects. METHODS: Participants from the Multicenter Osteoarthritis Study with knee CT and MRI scans were included. Presence of IA mineralization on CT was defined as a Boston University Calcium Knee Score >0 anywhere in the knee. Cartilage worsening on MRI was defined as any increase in the MRI OA Knee Score, including incident damage. We evaluated the association of whole-knee, compartment-specific (ie, medial or lateral), and subregion-specific (ie, location-matched) IA mineralization at baseline with cartilage worsening at two years' follow-up in the corresponding locations using binomial regression with generalized estimating equations, adjusting for age, sex, and body mass index (BMI). RESULTS: We included 1,673 participants (mean age 60 years, 56% female, mean BMI 29). Nine percent had any IA mineralization in the knee, and 47.4% had any cartilage worsening on follow-up. Mineralization of any tissue in the knee, regardless of location, was not associated with MRI cartilage worsening. However, cartilage mineralization was associated with 1.39 (95% confidence interval 1.04-1.88) times higher risk of cartilage worsening in the same compartment, with similar results in subregion-specific analysis. CONCLUSION: CT-detected IA mineralization in the cartilage was associated with higher risk of MRI cartilage worsening in the same compartment and subregion over two years. These findings suggest potential localized, tissue-specific effects of IA mineralization on cartilage pathology in knee OA.

Imaging Biomarkers of Osteoarthritis.

Currently no disease-modifying osteoarthritis drug has been approved for the treatment of osteoarthritis (OA) that can reverse, hold, or slow the progression of structural damage of OA-affected joints. The reasons for failure are manifold and include the heterogeneity of structural disease of the OA joint at trial inclusion, and the sensitivity of biomarkers used to measure a potential treatment effect.This article discusses the role and potential of different imaging biomarkers in OA research. We review the current role of radiography, as well as advances in quantitative three-dimensional morphological cartilage assessment and semiquantitative whole-organ assessment of OA. Although magnetic resonance imaging has evolved as the leading imaging method in OA research, recent developments in computed tomography are also discussed briefly. Finally, we address the experience from the Foundation for the National Institutes of Health Biomarker Consortium biomarker qualification study and the future role of artificial intelligence.

Modern low-field MRI.

This narrative review explores recent advancements and applications of modern low-field (≤ 1 Tesla) magnetic resonance imaging (MRI) in musculoskeletal radiology. Historically, high-field MRI systems (1.5 T and 3 T) have been the standard in clinical practice due to superior image resolution and signal-to-noise ratio. However, recent technological advancements in low-field MRI offer promising avenues for musculoskeletal imaging. General principles of low-field MRI systems are being introduced, highlighting their strengths and limitations compared to high-field counterparts. Emphasis is placed on advancements in hardware design, including novel magnet configurations, gradient systems, and radiofrequency coils, which have improved image quality and reduced susceptibility artifacts particularly in musculoskeletal imaging. Different clinical applications of modern low-field MRI in musculoskeletal radiology are being discussed. The diagnostic performance of low-field MRI in diagnosing various musculoskeletal pathologies, such as ligament and tendon injuries, osteoarthritis, and cartilage lesions, is being presented. Moreover, the discussion encompasses the cost-effectiveness and accessibility of low-field MRI systems, making them viable options for imaging centers with limited resources or specific patient populations. From a scientific standpoint, the amount of available data regarding musculoskeletal imaging at low-field strengths is limited and often several decades old. This review will give an insight to the existing literature and summarize our own experiences with a modern low-field MRI system over the last 3 years. In conclusion, the narrative review highlights the potential clinical utility, challenges, and future directions of modern low-field MRI, offering valuable insights for radiologists and healthcare professionals seeking to leverage these advancements in their practice.

CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis.

Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition. Biopsy-based single-cell RNA-sequencing analyses in experimental arthritis show that FAP signal reduction reflects a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalization) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalization). Spatial transcriptomics of human joints indicates that pro-resolving niches of CD200+DKK3+ fibroblasts cluster with type 2 innate lymphoid cells, whereas MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid cell phenotype and induced resolution of arthritis via CD200-CD200R1 signaling. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

Primary anterior cruciate ligament repair-morphological and quantitative assessment by 7-T MRI and clinical outcome after 1.5 years.

OBJECTIVES: The purpose of this study was to assess morphological and quantitative changes of the anterior cruciate ligament (ACL) and cartilage after ACL repair. METHODS: 7T MRI of the knee was acquired in 31 patients 1.5 years after ACL repair and in 13 controls. Proton density-weighted images with fat saturation (PD-fs) were acquired to assess ACL width, signal intensity, elongation, and fraying. T2/T2* mapping was performed for assessment of ACL and cartilage. Segmentation of the ACL, femoral, and tibial cartilage was carried out at 12 ROIs. The outcome evaluation consisted of the Lysholm Knee Score and International Knee Documentation Committee (IKDC) subjective score and clinical examination. RESULTS: ACL showed a normal signal intensity in 96.8% and an increased width in 76.5% after repair. Fraying occurred in 22.6% without having an impact on the clinical outcome (Lysholm score: 90.39 ± 9.75, p = 0.76 compared to controls). T2 analysis of the ACL revealed no difference between patients and controls (p = 0.74). Compared to controls, assessment of the femoral and tibial cartilage showed a significant increase of T2* times in all ROIs, except at the posterolateral femur. Patients presented a good outcome in clinical examination with a Lysholm score of 87.19 ± 14.89 and IKDC of 80.23 ± 16.84. CONCLUSION: T2 mapping results suggest that the tissue composition of the ACL after repair is similar to that of a native ACL after surgery, whereas the ACL exhibits an increased width. Fraying of the ACL can occur without having any impact on functional outcomes. T2* analysis revealed early degradation at the cartilage. CLINICAL RELEVANCE STATEMENT: MRI represents a noninvasive diagnostic tool for the morphological and compositional assessment of the anterior cruciate ligament after repair, whereas knowledge about post-surgical alterations is crucial for adequate imaging interpretation. KEY POINTS: • There has been renewed interest in repairing the anterior cruciate ligament with a proximally torn ligament. • T2 times of the anterior cruciate ligament do not differ between anterior cruciate ligament repair patients and controls. • T2 mapping may serve as a surrogate for the evaluation of the anterior cruciate ligament after repair.

A perspective on the evolution of semi-quantitative MRI assessment of osteoarthritis: Past, present and future.

OBJECTIVE: This perspective describes the evolution of semi-quantitative (SQ) magnetic resonance imaging (MRI) in characterizing structural tissue pathologies in osteoarthritis (OA) imaging research over the last 30 years. METHODS: Authors selected representative articles from a PubMed search to illustrate key steps in SQ MRI development, validation, and application. Topics include main scoring systems, reading techniques, responsiveness, reliability, technical considerations, and potential impact of artificial intelligence (AI). RESULTS: Based on original research published between 1993 and 2023, this article introduces available scoring systems, including but not limited to Whole-Organ Magnetic Resonance Imaging Score (WORMS) as the first system for whole-organ assessment of the knee and the now commonly used MRI Osteoarthritis Knee Score (MOAKS) instrument. Specific systems for distinct OA subtypes or applications have been developed as well as MRI scoring instruments for other joints such as the hip, the fingers or thumb base. SQ assessment has proven to be valid, reliable, and responsive, aiding OA investigators in understanding the natural history of the disease and helping to detect response to treatment. AI may aid phenotypic characterization in the future. SQ MRI assessment's role is increasing in eligibility and safety evaluation in knee OA clinical trials. CONCLUSIONS: Evidence supports the validity, reliability, and responsiveness of SQ MRI assessment in understanding structural aspects of disease onset and progression. SQ scoring has helped explain associations between structural tissue damage and clinical manifestations, as well as disease progression. While AI may support human readers to more efficiently perform SQ assessment in the future, its current application in clinical trials still requires validation and regulatory approval.

Association of biochemical markers with bone marrow lesion changes on imaging-data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

BACKGROUND: To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI. METHODS: Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0-3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iß, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined. RESULTS: Increases in serum CTX-I and urinary CTX-Iß over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline. CONCLUSIONS: Short-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iß hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.

Erosive hand osteoarthritis and sarcopenia: data from Osteoarthritis Initiative cohort.

OBJECTIVES: There is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study pioneers the exploration of the association between EHOA and sarcopenia, both of which are predominantly observed in the older adults. METHODS: Using the Osteoarthritis Initiative cohort, we selected hand OA (modified Kellgren and Lawrence (grade ≥2 in ≥1 hand joint) participants with radiographic central erosions in ≥1 joints (EHOA group) and propensity score-matched hand OA participants with no erosion (non-EHOA group). MRI biomarkers of thigh muscles were measured at baseline, year 2 and year 4 using a validated deep-learning algorithm. To adjust for 'local' effects of coexisting knee OA (KOA), participants were further stratified according to presence of radiographic KOA. The outcomes were the differences between EHOA and non-EHOA groups in the 4-year rate of change for both intramuscular adipose tissue (intra-MAT) deposition and contractile (non-fat) area of thigh muscles. RESULTS: After adjusting for potential confounders, 844 thighs were included (211 EHOA:633 non-EHOA; 67.1±7.5 years, female/male:2.9). Multilevel mixed-effect regression models showed that EHOA is associated a different 4-year rate of change in intra-MAT deposition (estimate, 95% CI: 71.5 mm2/4 years, 27.9 to 115.1) and contractile area (estimate, 95% CI: -1.8%/4 years, -2.6 to -1.0) of the Quadriceps. Stratified analyses showed that EHOA presence is associated with adverse changes in thigh muscle quality only in participants without KOA. CONCLUSIONS: EHOA is associated with longitudinal worsening of thigh muscle composition only in participants without concomitant KOA. Further research is needed to understand the systemic factors linking EHOA and sarcopenia, which unlike EHOA is modifiable through specific interventions.

[Current MR imaging of cartilage in the context of knee osteoarthritis (part 2) : Cartilage pathologies and their assessment]. / Aktuelle MRT-Bildgebung des Knorpels im Kontext der Gonarthrose (Teil 2) : Knorpelpathologien und deren Beurteilung.

High-quality magnetic resonance (MR) imaging is essential for the precise assessment of the knee joint and plays a key role in the diagnostics, treatment and prognosis. Intact cartilage tissue is characterized by a smooth surface, uniform tissue thickness and an organized zonal structure, which are manifested as depth-dependent signal intensity variations. Cartilage pathologies are identifiable through alterations in signal intensity and morphology and should be communicated based on a precise terminology. Cartilage pathologies can show hyperintense and hypointense signal alterations. Cartilage defects are assessed based on their depth and should be described in terms of their location and extent. The following symptom constellations are of overarching clinical relevance in image reading and interpretation: symptom constellations associated with rapidly progressive forms of joint degeneration and unfavorable prognosis, accompanying symptom constellations mostly in connection with destabilizing meniscal lesions and subchondral insufficiency fractures (accelerated osteoarthritis) as well as symptoms beyond the "typical" degeneration, especially when a discrepancy is observed between (minor) structural changes and (major) synovitis and effusion (inflammatory arthropathy).

How AI May Transform Musculoskeletal Imaging.

While musculoskeletal imaging volumes are increasing, there is a relative shortage of subspecialized musculoskeletal radiologists to interpret the studies. Will artificial intelligence (AI) be the solution? For AI to be the solution, the wide implementation of AI-supported data acquisition methods in clinical practice requires establishing trusted and reliable results. This implementation will demand close collaboration between core AI researchers and clinical radiologists. Upon successful clinical implementation, a wide variety of AI-based tools can improve the musculoskeletal radiologist's workflow by triaging imaging examinations, helping with image interpretation, and decreasing the reporting time. Additional AI applications may also be helpful for business, education, and research purposes if successfully integrated into the daily practice of musculoskeletal radiology. The question is not whether AI will replace radiologists, but rather how musculoskeletal radiologists can take advantage of AI to enhance their expert capabilities.

Osteoarthritis year in review 2023: Imaging.

PURPOSE: This narrative review summarizes the original research in the field of in vivo osteoarthritis (OA) imaging between 1 January 2022 and 1 April 2023. METHODS: A PubMed search was conducted using the following several terms pertaining to OA imaging, including but not limited to "Osteoarthritis / OA", "Magnetic resonance imaging / MRI", "X-ray" "Computed tomography / CT", "artificial intelligence /AI", "deep learning", "machine learning". This review is organized by topics including the anatomical structure of interest and modality, AI, challenges of OA imaging in the context of clinical trials, and imaging biomarkers in clinical trials and interventional studies. Ex vivo and animal studies were excluded from this review. RESULTS: Two hundred and forty-nine publications were relevant to in vivo human OA imaging. Among the articles included, the knee joint (61%) and MRI (42%) were the predominant anatomical area and imaging modalities studied. Marked heterogeneity of structural tissue damage in OA knees was reported, a finding of potential relevance to clinical trial inclusion. The use of AI continues to rise rapidly to be applied in various aspect of OA imaging research but a lack of generalizability beyond highly standardized datasets limit interpretation and wide-spread application. No pharmacologic clinical trials using imaging data as outcome measures have been published in the period of interest. CONCLUSIONS: Recent advances in OA imaging continue to heavily weigh on the use of AI. MRI remains the most important modality with a growing role in outcome prediction and classification.

Diagnostic Accuracy of Candidate Magnetic Resonance Imaging Knee Osteoarthritis Definitions Versus Radiograph in an Acute Anterior Cruciate Ligament Injury Cohort.

OBJECTIVE: We tested the diagnostic accuracy of previously proposed magnetic resonance imaging (MRI) osteoarthritis (OA) definitions in a cohort after acute anterior cruciate ligament (ACL) injury. METHODS: We studied participants with posteroanterior and lateral knee radiographs and MRI 5 years after ACL injury, scored using the Anterior Cruciate Ligament Osteoarthritis Score. Radiographic OA (ROA) was defined using Osteoarthritis Research Society International scoring of osteophytes and joint space narrowing considering medial/lateral tibiofemoral and patellofemoral compartments. We tested three candidate MRI OA definitions that performed well in an older adult cohort. "Multicenter Osteoarthritis Study (MOST) simple" required cartilage score ≥2 (range 0-6) and osteophyte score ≥2 (0-7); "MOST optional" included cartilage score ≥2, osteophyte score ≥2, and either bone marrow lesions (BMLs) ≥1 (0-3) or synovitis ≥2 (0-3). The third, a Delphi panel definition, included nonzero scores for cartilage, osteophyte, BMLs, meniscus, and other structures. We calculated sensitivity and specificity with 95% confidence intervals (95% CIs) for each MRI definition versus ROA. RESULTS: We included 113 participants (mean age 26 years, 26% female). At 5 years, 29 participants (26%) had ROA. "MOST simple" had a sensitivity of 52% (95% CI 33%-71%), and specificity of 76% (95% CI 66%-85%). Sensitivity and specificities for "MOST optional" were 28% (95% CI 29%-67%) and 83% (95% CI 74%-91%), respectively. The Delphi panel definition had a sensitivity of 48% (95% CI 29%-67%) and specificity of 77% (95% CI 67%-86%). CONCLUSION: Simple MRI-based OA definitions requiring at least cartilage damage and an osteophyte have low sensitivity and high specificity in young persons after knee injury.

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

OBJECTIVE: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. METHODS: 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. RESULTS: 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, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. CONCLUSIONS: 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.