Progression of Bone Marrow Lesions and the Development of Knee Osteoarthritis: Osteoarthritis Initiative Data.

Background Bone marrow lesions (BMLs) are a known risk factor for incident knee osteoarthritis (OA), and deep learning (DL) methods can assist in automated segmentation and risk prediction. Purpose To develop and validate a DL model for quantifying tibiofemoral BML volume on MRI scans in knees without radiographic OA and to assess the association between longitudinal BML changes and incident knee OA. Materials and Methods This retrospective study included knee MRI scans from the Osteoarthritis Initiative prospective cohort (February 2004-October 2015). The DL model, developed between August and October 2023, segmented the tibiofemoral joint into 10 subregions and measured BML volume in each subregion. Baseline and 4-year follow-up MRI scans were analyzed. Knees without OA at baseline were categorized into three groups based on 4-year BML volume changes: BML-free, BML regression, and BML progression. The risk of developing radiographic and symptomatic OA over 9 years was compared among these groups. Results Included were 3869 non-OA knees in 2430 participants (mean age, 59.5 years ± 9.0 [SD]; female-to-male ratio, 1.3:1). At 4-year follow-up, 2216 knees remained BML-free, 1106 showed an increase in BML volume, and 547 showed a decrease in BML volume. BML progression was associated with a higher risk of developing radiographic knee OA compared with remaining BML-free (hazard ratio [HR] = 3.0; P < .001) or BML regression (HR = 2.0; P < .001). Knees with BML progression also had a higher risk of developing symptomatic OA compared with BML-free knees (HR = 1.3; P < .001). Larger volume changes in BML progression were associated with a higher risk of developing both radiographic OA (HR = 2.0; P < .001) and symptomatic OA (HR = 1.7; P < .001). In almost all subchondral plates, especially the medial femur and tibia, BML progression was associated with a higher risk of developing both radiographic and symptomatic OA compared with remaining BML-free. Conclusion Knees with BML progression, according to subregion and extent of volume changes, were associated with an increased risk of OA compared with BML-free knees and knees with BML regression, highlighting the potential utility of monitoring BML volume changes in evaluating interventions to prevent OA development. ClinicalTrials.gov Identifier: NCT00080171 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Said and Sakly in this issue.

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.

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 ± 4.38, males: -8.83 ± 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.

Musculoskeletal CT Imaging: State-of-the-Art Advancements and Future Directions.

CT is one of the most widely used modalities for musculoskeletal imaging. Recent advancements in the field include the introduction of four-dimensional CT, which captures a CT image during motion; cone-beam CT, which uses flat-panel detectors to capture the lower extremities in weight-bearing mode; and dual-energy CT, which operates at two different x-ray potentials to improve the contrast resolution to facilitate the assessment of tissue material compositions such as tophaceous gout deposits and bone marrow edema. Most recently, photon-counting CT (PCCT) has been introduced. PCCT is a technique that uses photon-counting detectors to produce an image with higher spatial and contrast resolution than conventional multidetector CT systems. In addition, postprocessing techniques such as three-dimensional printing and cinematic rendering have used CT data to improve the generation of both physical and digital anatomic models. Last, advancements in the application of artificial intelligence to CT imaging have enabled the automatic evaluation of musculoskeletal pathologies. In this review, the authors discuss the current state of the above CT technologies, their respective advantages and disadvantages, and their projected future directions for various musculoskeletal applications.

Subchondral bone in knee osteoarthritis: bystander or treatment target?

The subchondral bone is an important structural component of the knee joint relevant for osteoarthritis (OA) incidence and progression once disease is established. Experimental studies have demonstrated that subchondral bone changes are not simply the result of altered biomechanics, i.e., pathologic loading. In fact, subchondral bone alterations have an impact on joint homeostasis leading to articular cartilage loss already early in the disease process. This narrative review aims to summarize the available and emerging imaging techniques used to evaluate knee OA-related subchondral bone changes and their potential role in clinical trials of disease-modifying OA drugs (DMOADs). Radiographic fractal signature analysis has been used to quantify OA-associated changes in subchondral texture and integrity. Cross-sectional modalities such as cone-beam computed tomography (CT), contrast-enhanced cone beam CT, and micro-CT can also provide high-resolution imaging of the subchondral trabecular morphometry. Magnetic resonance imaging (MRI) has been the most commonly used advanced imaging modality to evaluate OA-related subchondral bone changes such as bone marrow lesions and altered trabecular bone texture. Dual-energy X-ray absorptiometry can provide insight into OA-related changes in periarticular subchondral bone mineral density. Positron emission tomography, using physiological biomarkers of subchondral bone regeneration, has provided additional insight into OA pathogenesis. Finally, artificial intelligence algorithms have been developed to automate some of the above subchondral bone measurements. This paper will particularly focus on semiquantitative methods for assessing bone marrow lesions and their utility in identifying subjects at risk of symptomatic and structural OA progression, and evaluating treatment responses in DMOAD clinical trials.

Impact of immune status on the clinical characteristics, treatment outcomes and mortality of pulmonary nocardiosis: a retrospective analysis in a tertiary care hospital from a low to middle-income country.

Nocardiosis is an opportunistic infection that primarily targets the immunosuppressed. We investigate the differences in demographics and characteristics between immunosuppressed and immunocompetent patients with nocardiosis in a tertiary care hospital in Pakistan. Retrospective records were reviewed for patients diagnosed with pulmonary nocardiosis between 2010 and 2020. Immunosuppressed individuals were identified as those with autoimmune diseases, hematologic diseases and malignancies, HIV, immunosuppressant therapy, etc. Data collected included basic demographics, comorbid conditions, medication history, clinical presentation, radiological and microbiological data, and nocardiosis outcomes and complications. A total of 66 patients with nocardiosis were included in this study out of which 48 were immunosuppressed while 18 were immunocompetent. Both groups were compared for a number of variables including patient characteristics, underlying conditions, radiological findings, treatment regimen and outcomes. Immunosuppressed individuals were younger, and had higher rates of diabetes, chronic renal disease, chronic liver disease, higher platelet counts, surgical intervention, and longer hospital stays. Fever, dyspnea, and sputum production were the most common presentations. Nocardia asteroides was found to be the most common species of Nocardia overall. Nocardiosis presents differently in patients with immunosuppressed and immunocompetent patients consistent with previous studies. Nocardiosis should be considered in any patient presenting with treatment-resistant pulmonary or neurological symptoms.

Sarcoidosis: An experience from a tertiary care center in Karachi Pakistan.

OBJECTIVE: To assess the demographic and clinical characteristics and treatment of patients with sarcoidosis in tertiary care settings. METHODS: The descriptive retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from 2017 to 2019 of patients with established diagnosis of sarcoidosis. Data was collected on a predesigned proforma and it was analysed using SPSS 23. RESULTS: Of the 974 patients evaluated, sarcoidosis was established in 108(11.1%); 58(53.7%) of them being females. The overall mean age was 50.9±12.9 years. Hypertension 49(45.4%) and diabetes mellitus 37(34.3%) were the most frequent co-morbidities. Extra-pulmonary manifestations were found in 27(25%) patients; ophthalmic 9(33.3%), musculoskeletal 8(29.6%) and skin 7(25.9%). Prednisolone was the mainstay of treatment in 93(86.1%) patients. CONCLUSIONS: Sarcoidosis was not found to be rare in Pakistan.

Higher thyroid hormone has a negative association with lower limb lean body mass in euthyroid older adults: Analysis from the Baltimore Longitudinal study of aging.

Background: Hyperthyroidism is associated with lower lean body mass, as a result of catabolic actions of thyroid hormone. Therefore, higher thyroid hormone levels could be a factor in the development of sarcopenia and age associated functional decline. The relationship between thyroid hormone and muscle mass in ambulatory, euthyroid older adults is not known. Method: We used mixed-effects models to estimate the cross-sectional relationships (accounting for inter-person variability) between thyroid axis hormone measures and lower limb composition or sarcopenia at visits in the Baltimore Longitudinal Study of Aging (BLSA) at which DEXA scans were available and both thyrotropin (TSH) and free thyroxine (FT4) were in the reference range. Analyses were adjusted for levothyroxine use, age, race, sex, BMI, smoking, alcohol intake, cholesterol, and systolic blood pressure. Results: 1442 euthyroid participants (median age 68, 50% female, and 69% white) contributed to 5306 visits from 2003 to 2019. FT4 was negatively associated with lower limb lean mass (beta: 88.49; 95% Confidence Interval (CI): 122.78, -54.20; p < 0.001) and positively associated with sarcopenia (OR: 1.11%, 95% CI: 1.01, 1.22) in the whole cohort. Additionally, higher FT4 was associated with lower leg lean mass (beta: 66.79; 95% CI: 102.24, -31.33; p < 0.001) and sarcopenia (OR:1.09%, 95% CI:1.01, 1.18) in older adults, but not in younger adults alone. Conclusion: In euthyroid older adults, higher FT4 is associated with lower leg lean mass and higher odds of sarcopenia. Understanding the relationship between thyroid hormone and sarcopenia is needed to improve clinical decision-making and avoid functional decline from excess thyroid hormone use in older adults.

Radiographically detectable intra-articular mineralization: Predictor of knee osteoarthritis outcomes or only an indicator of aging? A brief report from the osteoarthritis initiative.

Objective: To determine the association between Intra-articular mineralization (IAM) and knee osteoarthritis (OA) outcomes stratified according to participants' age. Methods: Participants from the Osteoarthritis Initiative (OAI) with baseline radiographic OA (i.e., Kellgren-Lawrence grade ≥2 with Osteoarthritis Research Society International (OARSI) atlas joint space narrowing (JSN)) in either knee were identified. Both knees and dominant hand baseline radiographs were evaluated for the presence of IAM. Whole-grade OARSI-JSN radiographic progression and increased Western Ontario and McMaster universities osteoarthritis index scores of the knees with baseline radiographic OA (assessed annually) were defined as radiographic and symptomatic progression, respectively. Cox proportional-hazards and longitudinal multilevel regression models investigated radiographic and symptomatic progression, respectively. Results: 2010 participants with baseline radiographic OA in either one or both knees (N â€‹= â€‹2976) were identified. 178 participants had baseline IAM (hand radiographs â€‹= â€‹46, knee radiographs â€‹= â€‹166, both â€‹= â€‹34). An adjusted logistic regression model suggests an association between age and IAM (Odds Ratio: 1.06, 95% Confidence Interval (CI): 1.04-1.08). Presence of any IAM was not associated with whole-grade OARSI-JSN (Hazard Ratio (HR): 1.00, 95% CI: 0.73-1.37) or symptomatic progression (Estimated difference: 1.24, p-value: 0.13) in all participants. Using stratification analysis, in younger participants <60 years old, presence of any IAM was associated with radiographic progression (HR: 1.90, 95% CI: 1.01-3.60). Conclusion: Although the presence of any radiographic IAM increases with higher age and does not predict knee OA outcomes across the entire sample of OAI participants, it is associated with knee OA radiographic progression in participants aged <60.

Computed Tomography: State-of-the-Art Advancements in Musculoskeletal Imaging.

ABSTRACT: Although musculoskeletal magnetic resonance imaging (MRI) plays a dominant role in characterizing abnormalities, novel computed tomography (CT) techniques have found an emerging niche in several scenarios such as trauma, gout, and the characterization of pathologic biomechanical states during motion and weight-bearing. Recent developments and advancements in the field of musculoskeletal CT include 4-dimensional, cone-beam (CB), and dual-energy (DE) CT. Four-dimensional CT has the potential to quantify biomechanical derangements of peripheral joints in different joint positions to diagnose and characterize patellofemoral instability, scapholunate ligamentous injuries, and syndesmotic injuries. Cone-beam CT provides an opportunity to image peripheral joints during weight-bearing, augmenting the diagnosis and characterization of disease processes. Emerging CBCT technologies improved spatial resolution for osseous microstructures in the quantitative analysis of osteoarthritis-related subchondral bone changes, trauma, and fracture healing. Dual-energy CT-based material decomposition visualizes and quantifies monosodium urate crystals in gout, bone marrow edema in traumatic and nontraumatic fractures, and neoplastic disease. Recently, DE techniques have been applied to CBCT, contributing to increased image quality in contrast-enhanced arthrography, bone densitometry, and bone marrow imaging. This review describes 4-dimensional CT, CBCT, and DECT advances, current logistical limitations, and prospects for each technique.

Longitudinal MRI-defined Cartilage Loss and Radiographic Joint Space Narrowing Following Intra-Articular Corticosteroid Injection for Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Background: Intra-articular corticosteroid injections (IACS) are interventions which provide pain relief in knee osteoarthritis (OA). It remains unclear whether IACS have a deleterious effect on knee cartilage structure. Purpose: To estimate the effect of IACS on cartilage structure in patients with knee OA, using joint space width (JSW) (in radiographic studies), and cartilage thickness (in magnetic resonance imaging). Materials and methods: A literature search was performed to identify randomized control trials and observational studies published from inception to June 15, 2022. Studies were included if patients received IACS for knee OA, with a control arm. Given the different metrics used in reporting continuous variable outcomes among studies, pooled estimates for cartilage thickness change were assessed using standardized mean differences (defined as the difference between the means of the groups divided by a within-group standard deviation) to odds ratio transformation. Sensitivity analyses were conducted based on outcome metric, imaging modality, and number of injections. Results: Six studies (1437 participants) were identified. The estimated effect of IACS on cartilage structure revealed greater odds of cartilage structure worsening (Odds Ratio (OR): 2.01, 95% Confidence Interval (CI): 1.18,3.44). Sensitivity analyses revealed similar trends, with significant results for singular injections with preference to JSW (OR: 2.44, 95%CI: 1.23,4.82), radiographic outcomes with preference to KL grade (OR: 2.03, 95%CI: 1.01,4.10), binary outcomes with preference to KL grade (OR: 2.93, 95%CI: 1.18,7.25) and quantitative measures (Standardized Mean Differences (SMD): -0.34, 95%CI: -0.66, -0.02). Conclusions: IACS use may contribute to imaging features of knee cartilage loss. Further studies are warranted to investigate the underlying pathogenesis.

Predictive Value of Deep Learning-derived CT Pectoralis Muscle and Adipose Measurements for Incident Heart Failure: Multi-Ethnic Study of Atherosclerosis.

Purpose: To develop a deep learning algorithm capable of extracting pectoralis muscle and adipose measurements and to longitudinally investigate associations between these measurements and incident heart failure (HF) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods: MESA is a prospective study of subclinical cardiovascular disease characteristics and risk factors for progression to clinically overt disease approved by institutional review boards of six participating centers (ClinicalTrials.gov identifier: NCT00005487). All participants with adequate imaging and clinical data from the fifth examination of MESA were included in this study. Hence, in this secondary analysis, manual segmentations of 600 chest CT examinations (between the years 2010 and 2012) were used to train and validate a convolutional neural network, which subsequently extracted pectoralis muscle and adipose (intermuscular adipose tissue (IMAT), perimuscular adipose tissue (PAT), extramyocellular lipids and subcutaneous adipose tissue) area measurements from 3031 CT examinations using individualized thresholds for adipose segmentation. Next, 1781 participants without baseline HF were longitudinally investigated for associations between baseline pectoralis muscle and adipose measurements and incident HF using crude and adjusted Cox proportional hazards models. The full models were adjusted for variables in categories of demographic (age, race, sex, income), clinical/laboratory (including physical activity, BMI, and smoking), CT (coronary artery calcium score), and cardiac MRI (left ventricular ejection fraction and mass (% of predicted)) data. Results: In 1781 participants (median age, 68 (IQR,61, 75) years; 907 [51%] females), 41 incident HF events occurred over a median 6.5-year follow-up. IMAT predicted incident HF in unadjusted (hazard ratio [HR]:1.14; 95% CI: 1.03-1.26) and fully adjusted (HR:1.16, 95% CI: 1.03-1.31) models. PAT also predicted incident HF in crude (HR:1.19; 95% CI: 1.06-1.35) and fully adjusted (HR:1.25; 95% CI: 1.07-1.46) models. Conclusion: The study demonstrates that fast and reliable deep learning-derived pectoralis muscle and adipose measurements are obtainable from conventional chest CT, which may be predictive of incident HF.©RSNA, 2023.