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 BMI over four years. Using a previously validated deep-learning algorithm, we measured 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.

Adiposity and cartilage lesions following ACL reconstruction.

OBJECTIVE: To determine if global, central, or peripheral adiposity is associated with prevalent and worsening cartilage lesions following anterior cruciate ligament reconstruction (ACLR). METHODS: In 107 individuals one-year post-ACLR, adiposity was assessed globally (body mass index), centrally (waist circumference), and peripherally (knee subcutaneous adipose tissue thickness) from magnetic resonance imaging (MRI). Tibiofemoral and patellofemoral cartilage lesions were assessed from knee MRIs at 1- and 5-years post-ACLR. Poisson regression evaluated the relation of adiposity with prevalent and worsening tibiofemoral and patellofemoral cartilage lesions adjusting for age, sex, and activity level. RESULTS: The prevalence ratios of adiposity with tibiofemoral (presence in 49%) and patellofemoral (44%) cartilage lesions ranged from 0.99 to 1.03. Adiposity was more strongly associated with longitudinal changes in tibiofemoral (worsening in 21%) and patellofemoral (44%) cartilage lesions. One-unit increase in global (kg/m2), central (cm), and peripheral (mm) adiposity was associated with a higher risk of worsening tibiofemoral cartilage lesions by 17% (risk ratios [95% confidence interval (CI)]: 1.17 [1.09 to 1.23]), 5% (1.05 [1.02 to 1.08]), and 9% (1.09 [1.03 to 1.16]), and patellofemoral cartilage lesions by 5% (1.05 [1.00 to 1.12]), 2% (1.02 [1.00 to 1.04]) and 2% (1.02 [1.00 to 1.04]), respectively. CONCLUSION: Greater adiposity was a risk factor for worsening cartilage lesions up to 5 years post-ACLR. Clinical interventions aimed at mitigating excess adiposity may be beneficial in preventive approaches for early post-traumatic osteoarthritis.

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.

Transcatheter arterial tendinopathy embolization as a treatment for painful and refractory tendinopathy: a systematic review and meta-analysis.

OBJECTIVE: Transcatheter arterial embolization (TAE) is a novel minimally invasive therapy for painful tendinopathy in patients with pain refractory to conservative management. The purpose of this study was to evaluate evidence on the efficacy of TAE for tendinopathy related pain. MATERIALS AND METHODS: Using Embase, PubMed, and Web of Science, a systematic review and meta-analysis was performed to identify studies evaluating TAE for painful tendinopathy. The primary outcome measure was change in pain scale score at 6 months. A Ratio of Means (ROM) was used to compare the effect size post treatment as compared to baseline. The Visual Analog Scale (VAS) was used as the metric for comparison. RESULTS: After screening titles, abstracts, and the full text, 5 studies met inclusion criteria. A total of 97 tendinopathy embolization procedures performed in 74 patients were included. Patients who underwent TAE demonstrated declines in VAS ROM at 1 day 0.53 [95% CI 0.31,0.88], 1 week (0.51 [95% CI 0.32,0.79]), 1 month (0.45 [95% CI 0.29, 0.71]), 3-4 months (0.33 [95% CI 0.22,0.48]), and 6 months following embolization (0.18[95% CI 0.13,0.26]), respectively. DISCUSSION: TAE provides substantial short-term reductions in pain scores for patients suffering with refractory tendinopathy related pain of the rotator cuff, elbow extensor and flexor, Achilles, and patellar tendons.

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.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older East Asian women should be lower than the value for Caucasians.

For Caucasian women, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) cutpoint value for classifying osteoporosis is 80 mg/ml. At the age of approximate 78 years, US Caucasian women QCT LS BMD population mean is 80 mg/ml, while that of Chinese women and Japanese women is around 50 mg/ml. Correlation analyses show, for Chinese women and Japanese women, QCT LS BMD of 45 mg/ml corresponds to the dual-energy X-ray absorptiometry cutpoint value for classifying osteoporosis. For Chinese and Japanese women, if QCT LS BMD 80 mg/ml is used as the threshold to classify osteoporosis, then the specificity of classifying subjects with vertebral fragility fracture into the osteoporotic group is low, whereas threshold of 45 mg/ml approximately achieve a similar separation for women with and without vertebral fragility fracture as the reports for Caucasian women. Moreover, by using 80mg/ml as the cutpoint value, LS QCT leads to excessively high prevalence of osteoporosis for Chinese women, with the discordance between hip dual-energy X-ray absorptiometry and LS QCT measures far exceeding expectation. Considering the different bone properties and the much lower prevalence of fragility fractures in the East Asian women compared with Caucasians, we argue that the QCT cutpoint value for classifying osteoporosis among older East Asian women will be close to and no more than 50 mg/ml LS BMD. We suggest that it is also imperative the QCT osteoporosis classification criterion for East Asian male LS, and male and female hips be re-examined.

Dual energy computed tomography cannot effectively differentiate between calcium pyrophosphate and basic calcium phosphate diseases in the clinical setting.

Background: Recent reports suggested that dual-energy CT (DECT) may help discriminate between different types of calcium phosphate crystals in vivo, which would have important implications for the characterization of crystal deposition occurring in osteoarthritis. Purpose: Our aim was to test the hypothesis that DECT can effectively differentiate basic calcium phosphate (BCP) from calcium pyrophosphate (CPP) deposition diseases. Methods: Discarded tissue after total knee replacement specimens in a 71 year-old patient with knee osteoarthritis and chondrocalcinosis was scanned using DECT at standard clinical parameters. Specimens were then examined on light microscopy which revealed CPP deposition in 4 specimens (medial femoral condyle, lateral tibial plateau and both menisci) without BCP deposition. Regions of interest were placed on post-processed CT images using Rho/Z maps (Syngo.via, Siemens Healthineers, VB10B) in different areas of CPP deposition, trabecular bone BCP (T-BCP) and subchondral bone plate BCP (C-BCP). Results: Dual Energy Index (DEI) of CPP was 0.12 (SD â€‹= â€‹0.02) for reader 1 and 0.09 (SD â€‹= â€‹0.03) for reader 2, The effective atomic number (Zeff) of CPP was 10.83 (SD â€‹= â€‹0.44) for reader 1 and 10.11 (SD â€‹= â€‹0.66) for reader 2. Nearly all DECT parameters of CPP were higher than those of T-BCP, lower than those of C-BCP, and largely overlapping with Aggregate-BCP (aggregate of T-BCP and C-BCP). Conclusion: Differentiation of different types of calcium crystals using DECT is not feasible in a clinical setting.

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.

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.

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.

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.

East Asians' T-scores for the diagnosis of osteoporosis should be calculated using ethnicity- and gender-specific BMD reference ranges: justifications.

The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality.

Revision of the 1994 World Health Organization T-score definition of osteoporosis for use in older East Asian women and men to reconcile it with their lifetime risk of fragility fracture.

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden.

Artificial intelligence in osteoarthritis detection: A systematic review and meta-analysis.

OBJECTIVES: As an increasing number of studies apply artificial intelligence (AI) algorithms in osteoarthritis (OA) detection, we performed a systematic review and meta-analysis to pool the data on diagnostic performance metrics of AI, and to compare them with clinicians' performance. MATERIALS AND METHODS: A search in PubMed and Scopus was performed to find studies published up to April 2022 that evaluated and/or validated an AI algorithm for the detection or classification of OA. We performed a meta-analysis to pool the data on the metrics of diagnostic performance. Subgroup analysis based on the involved joint and meta-regression based on multiple parameters were performed to find potential sources of heterogeneity. The risk of bias was assessed using Prediction Model Study Risk of Bias Assessment Tool reporting guidelines. RESULTS: Of the 61 studies included, 27 studies with 91 contingency tables provided sufficient data to enter the meta-analysis. The pooled sensitivities for AI algorithms and clinicians on internal validation test sets were 88% (95% confidence interval [CI]: 86,91) and 80% (95% CI: 68,88) and pooled specificities were 81% (95% CI: 75,85) and 79% (95% CI: 80,85), respectively. At external validation, the pooled sensitivity and specificity for AI algorithms were 94% (95% CI: 90,97) and 91% (95% CI: 77,97), respectively. CONCLUSION: Although the results of this meta-analysis should be interpreted with caution due to the potential pitfalls in the included studies, the promising role of AI as a diagnostic adjunct to radiologists is indisputable.

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.