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.

Screening for Asymptomatic Osteonecrosis of the Hip in Systemic Lupus Erythematous: A Systematic Review and Meta-Analysis of MRI-Based Prevalence.

Objective. This paper aims to estimate asymptomatic hip osteonecrosis prevalence in SLE patients using MRI examination and to determine the prevalence among higher risk subpopulations. Materials and Methods. PubMed, Embase, Cochrane, and SCOPUS were searched from inception to May 9th, 2023. Studies on patients who were clinically diagnosed with systemic lupus erythematosus without reported symptoms attributable to hip osteonecrosis were included. Two independent reviewers extracted data and assessed the risk of bias. Data collected from each study include the study year, the number of hips screened, the number of hips with osteonecrosis, demographics, laboratory data, medications, follow-up time, radiological protocols, and MRI-based osteonecrosis detection and grading criteria. Results. Eleven eligible studies including 503 participants (15-35 years old; 74-100% female) with SLE were identified. Significant risk of bias was determined in one study. The overall prevalence of osteonecrosis of the hip was found to be 14% (184/1006 hip joints, 95% confidence interval: 7-22%, number needed to scan: 7.1). SLE patients who received corticosteroid treatment had a higher prevalence of asymptomatic hip osteonecrosis (18%) compared to non-corticosteroid users (0%, p-value < 0.01). Additionally, meta-regression results revealed that daily corticosteroid dose was associated with increased prevalence of asymptomatic osteonecrosis (0.5%/milligram, p-value < 0.01). Conclusions. The high prevalence of asymptomatic hip osteonecrosis in SLE patients raises concerns about the timeliness of interventions. The limitations of this study include a relatively low number of identified studies; and one study lacked full-text availability.

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.

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.

Parathyroid hormone treatment partially reverses endplate remodeling and attenuates low back pain in animal models of spine degeneration.

Low back pain (LBP) is one of the most prevalent diseases affecting quality of life, with no disease-modifying therapy. During aging and spinal degeneration, the balance between the normal endplate (EP) bilayers of cartilage and bone shifts to more bone. The aged/degenerated bony EP has increased porosity because of osteoclastic remodeling activity and may be a source of LBP due to aberrant sensory innervation within the pores. We used two mouse models of spinal degeneration to show that parathyroid hormone (PTH) treatment induced osteogenesis and angiogenesis and reduced the porosity of bony EPs. PTH increased the cartilaginous volume and improved the mechanical properties of EPs, which was accompanied by a reduction of the inflammatory factors cyclooxygenase-2 and prostaglandin E2. PTH treatment furthermore partially reversed the innervation of porous EPs and reversed LBP-related behaviors. Conditional knockout of PTH 1 receptors in the nucleus pulposus (NP) did not abolish the treatment effects of PTH, suggesting that the NP is not the primary source of LBP in our mouse models. Last, we showed that aged rhesus macaques with spontaneous spinal degeneration also had decreased EP porosity and sensory innervation when treated with PTH, demonstrating a similar mechanism of PTH action on EP sclerosis between mice and macaques. In summary, our results suggest that PTH treatment could partially reverse EP restructuring during spinal regeneration and support further investigation into this potentially disease-modifying treatment strategy for LBP.

CT-derived pectoralis composition and incident pneumonia hospitalization using fully automated deep-learning algorithm: multi-ethnic study of atherosclerosis.

BACKGROUND: Pneumonia-related hospitalization may be associated with advanced skeletal muscle loss due to aging (i.e., sarcopenia) or chronic illnesses (i.e., cachexia). Early detection of muscle loss may now be feasible using deep-learning algorithms applied on conventional chest CT. OBJECTIVES: To implement a fully automated deep-learning algorithm for pectoralis muscle measures from conventional chest CT and investigate longitudinal associations between these measures and incident pneumonia hospitalization according to Chronic Obstructive Pulmonary Disease (COPD) status. MATERIALS AND METHODS: This analysis from the Multi-Ethnic Study of Atherosclerosis included participants with available chest CT examinations between 2010 and 2012. We implemented pectoralis muscle composition measures from a fully automated deep-learning algorithm (Mask R-CNN, built on the Faster Region Proposal Network (R-) Convolutional Neural Network (CNN) with an extension for mask identification) for two-dimensional segmentation. Associations between CT-derived measures and incident pneumonia hospitalizations were evaluated using Cox proportional hazards models adjusted for multiple confounders which include but are not limited to age, sex, race, smoking, BMI, physical activity, and forced-expiratory-volume-at-1 s-to-functional-vital-capacity ratio. Stratification analyses were conducted based on baseline COPD status. RESULTS: This study included 2595 participants (51% female; median age: 68 (IQR: 61, 76)) CT examinations for whom we implemented deep learning-derived measures for longitudinal analyses. Eighty-six incident pneumonia hospitalizations occurred during a median 6.67-year follow-up. Overall, pectoralis muscle composition measures did not predict incident pneumonia. However, in fully-adjusted models, only among participants with COPD (N = 507), CT measures like extramyocellular fat index (hazard ratio: 1.98, 95% CI: 1.22, 3.21, p value: 0.02), were independently associated with incident pneumonia. CONCLUSION: Reliable deep learning-derived pectoralis muscle measures could predict incident pneumonia hospitalization only among participants with known COPD. CLINICAL RELEVANCE STATEMENT: Pectoralis muscle measures obtainable at zero additional cost or radiation exposure from any chest CT may have independent predictive value for clinical outcomes in chronic obstructive pulmonary disease patients. KEY POINTS: •Identification of independent and modifiable risk factors of pneumonia can have important clinical impact on patients with chronic obstructive pulmonary disease. •Opportunistic CT measures of adipose tissue within pectoralis muscles using deep-learning algorithms can be quickly obtainable at zero additional cost or radiation exposure. •Deep learning-derived pectoralis muscle measurements of intermuscular fat and its subcomponents are independently associated with subsequent incident pneumonia hospitalization.

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.

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.

A rare case report of tenosynovial chondromatosis of the semimembranosus-medial collateral ligament bursa.

BACKGROUND: Synovial chondromatosis is an uncommon metaplastic process of the synovial lining that results in the formation of cartilaginous nodules within joints or their associated bursae or tendon sheaths. Radiologic evidence of mineralized bodies within these structures is typically pathognomonic for this condition. Extraarticular chondromatosis is rarer than intraarticular chondromatosis, and the knee is affected less frequently than the smaller joints of the hands and feet. To our knowledge, no reports describing this condition in the semimembranosus-medial collateral ligament (SM-MCL) bursa have been published. CASE PRESENTATION: We describe a case of tenosynovial chondromatosis in a 37-year-old woman. The case was atypical for both the location within the SM-MCL bursa and the paucity of radiodense or hypointense changes to support a clinical suspicion of chondroid metaplasia on radiographs and T2-weighted MRI, respectively. Recreational weightlifting and swimming by the patient were impaired by chronic pain, and restricted range of motion of the ipsilateral knee persisted despite extensive skilled physical therapy and injections of both corticosteroids and platelet-rich plasma. Thirteen months after a diagnostic and therapeutic knee arthroscopy, open surgical excision of the SM-MCL bursal body was performed, and knee pain and range of motion improved by the 6-week postoperative reevaluation. Pathologic evaluation of the excised tissue was consistent with tenosynovial chondromatosis. CONCLUSIONS: Synovial chondromatosis should be considered in the differential diagnosis for recalcitrant bursitis, even in the absence of classic imaging findings.

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.

Levothyroxine use and longitudinal changes in thigh muscles in at-risk participants for knee osteoarthritis: preliminary analysis from Osteoarthritis Initiative cohort.

BACKGROUND: We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence. METHODS: Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes. RESULTS: We included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: - 16.06 mm2/year, - 26.70 to - 5.41) but not thigh muscles' composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15-2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19-3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use. CONCLUSIONS: Our exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.

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.

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

OBJECTIVES: We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms. METHODS: The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM-KOA worsening association is mediated through preceding muscle degeneration. RESULTS: After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI -0.16%/year, -0.25 to -0.07, and -0.21%/year, -0.33 to -0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18-2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM. CONCLUSIONS: Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA. KEY POINTS: • Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms. • As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

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.

Quantitative Dual-Energy Imaging of Bone Marrow Edema Using Multisource Cone-Beam CT with Model-Based Decomposition.

Purpose: We investigated the feasibility of dual-energy (DE) detection of bone marrow edema (BME) using a dedicated extremity cone-beam CT (CBCT) with a unique three-source x-ray unit. The sources can be operated at different energies to enable single-scan DE acquisitions. However, they are arranged parallel to the axis of rotation, resulting in incomplete sampling and precluding the application of DE projection-domain decompositions (PDD) for beam-hardening reduction. Therefore, we propose a novel combination of a model-based "one-step" DE two-material decomposition followed by a constrained image-domain change-of-basis to obtain virtual non-calcium (VNCa) images for BME detection. Methods: DE projections were obtained using an "alternating-kV" protocol by operating the peripheral two sources of the CBCT system at low-energy (60 kV, 0.105 mAs/frame) and the central source at high-energy (100 kV, 0.028 mAs/frame), for a total of 600 frames over 216° of gantry rotation. Projections were processed with detector lag, glare and fast Monte Carlo (MC)-based iterative scatter corrections. Model-based material decomposition (MBMD) was then implemented to obtain aluminum (Al) and polyethylene (PE) volume fraction images with minimal beam-hardening. Statistical ray weights in MBMD were modified to account for regions with highly oblique sampling by the peripheral sources. To generate the VNCa maps, image-domain decomposition (IDD) constrained by the volume conservation principle (VCP) was performed to convert the Al and PE MBMD images into volume fractions of water, fat and cortical bone. Accuracy of BME detection was evaluated using physical phantom data acquired on the multi-source extremity CBCT scanner. Results: The proposed framework estimated the volume of BME with ~10% error. The MC-based scatter corrections and the modified MBMD ray weights were essential to achieve such performance - the error without MC scatter corrections was >30%, whereas the uniformity of estimated VNCa images was 3x improved using the modified weights compared to the conventional weights. Conclusions: The proposed DE decomposition framework was able to overcome challenges of high scatter and incomplete sampling to achieve BME detection on a CBCT system with axially-distributed x-ray sources.

Patterns of progression differ between Kellgren-Lawrence 2 and 3 knees fulfilling different definitions of a cartilage-meniscus phenotype in the Foundation for National Institutes of Health Osteoarthritis Biomarkers study (FNIH).

Objective: Aim was to describe three definitions for an MRI-defined cartilage-meniscus phenotype and to report phenotypic progression in Kellgren-Lawrence (KL) 2 and 3 knees over 48 months. Methods: The study sample was a nested case-control study with knees showing either 1) radiographic and pain progression ("composite" case), 2) radiographic progression only, 3) pain progression only, and 4) no progression. MRI was performed on 3T systems. MRIs were read according to the MOAKS system. Knees were classified as having the cartilage-meniscus phenotype according to three modified ROAMES (Rapid OsteoArthritis MRI Eligibility Score) definitions (D): 1) â€‹≤ â€‹2.2 (10-75% of the region of cartilage surface area with 10-75% affected by full thickness loss), i.e. 'D1' 2) ≤ 2.1 (10-75% of the region of cartilage surface area with <10% affected by full thickness loss), i.e. 'D2' and 3) ≤ 2.0 (10-75% of the region of cartilage surface area without full thickness loss), i.e. 'D3'. The odds of being a composite case for those with vs. without each definition was determined using logistic regression. Results: 485 knees were included. For KL2 knees 191 (64%) knees fulfilled D1 criteria, 183 (62%) D2 and 167 (56%) D3. For KL3 these numbers were 164 (87%), 103 (55%) and 77 (41%). Odds for being a composite case for KL2 knees were 2.52 (95% CI 1.40,4.54) for D1, 1.93 (95% CI 1.11,3.35) for D2 and 1.92 (95% CI 1.13,3.28) for D3. For KL3 knees odds were 0.32 (95% CI 0.13,0.78) for D1, 0.56 (95% CI 0.31,1.01) for D2 and 0.49 (95% CI 0.26,0.91) for D3. Conclusion: Increased odds for progression are seen for KL2 knees for all definitions, while this was not observed for KL3 knees. KL3 knees exceeding the maximum damage thresholds and not fulfilling the phenotypic definitions are still likely to experience further progression.

Senescent preosteoclast secretome promotes metabolic syndrome associated osteoarthritis through cyclooxygenase 2.

Background: Metabolic syndrome-associated osteoarthritis (MetS-OA) is a distinct osteoarthritis phenotype defined by the coexistence of MetS or its individual components. Despite the high prevalence of MetS-OA, its pathogenic mechanisms are unclear. The aim of this study was to determine the role of cellular senescence in the development of MetS-OA. Methods: Analysis of the human osteoarthritis initiative (OAI) dataset was conducted to investigate the MRI subchondral bone features of MetS-human OA participants. Joint phenotype and senescent cells were evaluated in two MetS-OA mouse models: high-fat diet (HFD)-challenged mice and STR/Ort mice. In addition, the molecular mechanisms by which preosteoclasts become senescent as well as how the senescent preosteoclasts impair subchondral bone microenvironment were characterized using in vitro preosteoclast culture system. Results: Humans and mice with MetS are more likely to develop osteoarthritis-related subchondral bone alterations than those without MetS. MetS-OA mice exhibited a rapid increase in joint subchondral bone plate and trabecular thickness before articular cartilage degeneration. Subchondral preosteoclasts undergo senescence at the pre- or early-osteoarthritis stage and acquire a unique secretome to stimulate osteoblast differentiation and inhibit osteoclast differentiation. Antagonizing preosteoclast senescence markedly mitigates pathological subchondral alterations and osteoarthritis progression in MetS-OA mice. At the molecular level, preosteoclast secretome activates COX2-PGE2, resulting in stimulated differentiation of osteoblast progenitors for subchondral bone formation. Administration of a selective COX2 inhibitor attenuated subchondral bone alteration and osteoarthritis progression in MetS-OA mice. Longitudinal analyses of the human Osteoarthritis Initiative (OAI) cohort dataset also revealed that COX2 inhibitor use, relative to non-selective nonsteroidal antiinflammatory drug use, is associated with less progression of osteoarthritis and subchondral bone marrow lesion worsening in participants with MetS-OA. Conclusions: Our findings suggest a central role of a senescent preosteoclast secretome-COX2/PGE2 axis in the pathogenesis of MetS-OA, in which selective COX2 inhibitors may have disease-modifying potential. Funding: This work was supported by the National Institutes of Health grant R01AG068226 and R01AG072090 to MW, R01AR079620 to SD, and P01AG066603 to XC.