Osteoarthritis year in review 2022: imaging.

PURPOSE: This narrative review summarizes original research focusing on imaging in osteoarthritis (OA) published between April 1st 2021 and March 31st 2022. We only considered English publications that were in vivo human studies. METHODS: The PubMed, Medline, Embase, Scopus, and ISI Web of Science databases were searched for "Osteoarthritis/OA" studies based on the search terms: "Radiography", "Ultrasound/US", "Computed Tomography/CT", "DXA", "Magnetic Resonance Imaging/MRI", "Artificial Intelligence/AI", and "Deep Learning". This review highlights the anatomical focus of research on the structures within the tibiofemoral, patellofemoral, hip, and hand joints. There is also a noted focus on artificial intelligence applications in OA imaging. RESULTS: Over the last decade, the increasing trend of using open-access large databases has reached a plateau (from 17 to 37). Compositional MRI has had the most prominent use in OA imaging and its biomarkers have been used in the detection of preclinical OA and prediction of OA outcomes. Most noteworthy, there has been an accelerated rate of publications on the implications of artificial intelligence, used in developing prediction models and performing trabecular texture analysis, in OA imaging (from 17 to 154). CONCLUSIONS: While imaging has maintained its key role in OA research, publication trends have shown an emphasis on the integration of AI. During the past year, MRI has maintained the highest prevalence in usage while US and CT remain as readily available modalities. Finally, there has been a notable uptake in the development and validation of AI techniques used to perform texture analysis and predict OA progression.

Imaging in Osteoarthritis.

Osteoarthritis (OA) is the most frequent form of arthritis with major implications on both individual and public health care levels. The field of joint imaging, and particularly magnetic resonance imaging (MRI), has evolved rapidly due to the application of technical advances to the field of clinical research. This narrative review will provide an introduction to the different aspects of OA imaging aimed at an audience of scientists, clinicians, students, industry employees, and others who are interested in OA but who do not necessarily focus on OA. The current role of radiography and recent advances in measuring joint space width will be discussed. The status of cartilage morphology assessment and evaluation of cartilage biochemical composition will be presented. Advances in quantitative three-dimensional morphologic cartilage assessment and semi-quantitative whole-organ assessment of OA will be reviewed. Although MRI has evolved as the most important imaging method used in OA research, other modalities such as ultrasound, computed tomography, and metabolic imaging play a complementary role and will also be discussed.

Deep learning risk assessment models for predicting progression of radiographic medial joint space loss over a 48-MONTH follow-up period.

OBJECTIVE: To develop and evaluate deep learning (DL) risk assessment models for predicting the progression of radiographic medial joint space loss using baseline knee X-rays. METHODS: Knees from the Osteoarthritis Initiative without and with progression of radiographic joint space loss (defined as ≥ 0.7 mm decrease in medial joint space width measurement between baseline and 48-month follow-up X-rays) were randomly stratified into training (1400 knees) and hold-out testing (400 knees) datasets. A DL network was trained to predict the progression of radiographic joint space loss using the baseline knee X-rays. An artificial neural network was used to develop a traditional model for predicting progression utilizing demographic and radiographic risk factors. A combined joint training model was developed using a DL network to extract information from baseline knee X-rays as a feature vector, which was further concatenated with the risk factor data vector. Area under the curve (AUC) analysis was performed using the hold-out test dataset to evaluate model performance. RESULTS: The traditional model had an AUC of 0.660 (61.5% sensitivity and 64.0% specificity) for predicting progression. The DL model had an AUC of 0.799 (78.0% sensitivity and 75.5% specificity), which was significantly higher (P < 0.001) than the traditional model. The combined model had an AUC of 0.863 (80.5% sensitivity and specificity), which was significantly higher than the DL (P = 0.015) and traditional (P < 0.001) models. CONCLUSION: DL models using baseline knee X-rays had higher diagnostic performance for predicting the progression of radiographic joint space loss than the traditional model using demographic and radiographic risk factors.

Application of a Novel Ultra-High Resolution Multi-Detector CT in Quantitative Imaging of Trabecular Microstructure.

PURPOSE: To evaluate the performance of a novel ultra-high resolution multi-detector CT scanner (Canon Aquilion Precision UHR CT), capable of visualizing ~150 µm details, in quantitative assessment of bone microarchitecture. Compared to conventional CT, the spatial resolution of UHR CT begins to approach the size of the trabeculae. This might enable measurements of microstructural correlates of osteoporosis, osteoarthritis, and other bone disease. METHODS: The UHR CT system features a 160-row x-ray detector with 250×250 µm pixels (measured at isocenter) and a custom-designed x-ray source with a 0.4×0.5 mm focal spot. Visualization of high contrast details down to ~150 µm has been achieved on this device, which is now commercially available for clinical use. To evaluate the performance of UHR CT in quantification of bone microstructure, we imaged a variety of human bone samples (including ulna, radius, and vertebrae) embedded in a ~16 cm diameter plastic cylinder and in an anthropomorphic thorax phantom (QRM-Thorax, QRM Gmbh). Helical UHR CT acquisitions (120 kVp tube voltage) were acquired at scan exposures of 375 mAs - 5 mAs. For comparison, the samples were also imaged using a Normal Resolution (NR) mode available on the scanner, involving 500 µm slice thickness, exposure of 50 mAs, and a focal spot of 0.6×1.3 mm. We obtained micro-CT (µCT) of the bone samples at ~28 µm voxel size as a gold-standard reference. Geometric measurements of bone microstructure were performed in 17 regions-of-interests (ROIs) distributed throughout the bones of the phantoms; image registration was used to place the ROIs at corresponding locations in the UHR CT and NR CT. Trabecular thickness Tb.Th, spacing Tb.Sp, and Bone Volume fraction BvTv were obtained. The UHR and NR imaging protocols were compared terms of correlations to µCT and error of trabecular measurements. The effect of dose on trabecular morphometry was also studied for the UHR CT. Furthermore, we evaluated the sensitivity of texture features of trabecular bone (recently proposed as an alternative to geometric indices of microstructure) to imaging protocol. Image texture evaluation was performed using ~150 regions of interest (ROIs) across all bone samples. Three-dimensional Gray Level Co-occurrence Matrix (GLCM) and Gray Level Run Length Matrix (GLRM) features were extracted for each ROI. We analyzed correlation and concordance correlation coefficient (CCC) of the mean ROI values of texture features obtained using the UHR and NR modes. RESULTS: UHR CT reconstructions of bone samples clearly demonstrated improved visualization of the trabeculae compared to NR CT. UHR CT achieved substantially better correlations for all three metrics of bone microstructure, in particular for BvTv (correlation coefficient of 0.91 for UHR CT compared to 0.84 for NR CT) and TbSp (correlation of 0.74 for UHR CT and 0.047 for NR CT). The error obtained with UHR CT was generally smaller than that of NR CT. For TbSp, the mean deviation from µCT (averaged across all bone samples) was only ~0.07 for UHR CT, compared to 0.25 for NR CT. Analysis of reproducibility of texture features of trabecular bone between UHR CT and NR CT revealed fair correlations (>0.7) for the majority of GLCM features, but relatively poor CCC (e.g. 0.02 for Energy and 0.04 for Entropy). The magnitude of texture metrics is particularly affected by the enhanced spatial resolution of UHR CT. CONCLUSION: The recently introduced UHR CT achieves improved correlation and reduced error in measurements of trabecular bone microstructure compared to conventional resolution CT. Future development of diagnostic strategies based on textural biomarkers derived from UHR CT will need to account for potential sensitivity of texture features to image resolution.

Osteoarthritis year in review 2019: imaging.

OBJECTIVE: To provide a narrative review of original articles on osteoarthritis (OA) imaging published between April 1, 2018 and March 30, 2019. METHODS: All original research articles on OA imaging published in English between April 1, 2018 and March 30, 2019 were identified using a PubMed database search. The search terms of "Osteoarthritis" or "OA" were combined with the search terms "Radiography", "X-Rays", "Magnetic Resonance Imaging", "MRI", "Ultrasound", "US", "Computed Tomography", "Dual Energy X-Ray Absorptiometry", "DXA", "DEXA", "CT", "Nuclear Medicine", "Scintigraphy", "Single-Photon Emission Computed Tomography", "SPECT", "Positron Emission Tomography", "PET", "PET-CT", or "PET-MRI". Articles were reviewed to determine relevance based upon the following criteria: 1) study involved human subjects with OA or risk factors for OA and 2) study involved imaging to evaluate OA disease status or OA treatment response. Relevant articles were ranked according to scientific merit, with the best publications selected for inclusion in the narrative report. RESULTS: The PubMed search revealed a total of 1257 articles, of which 256 (20.4%) were considered relevant to OA imaging. Two-hundred twenty-six (87.1%) articles involved the knee joint, while 195 (76.2%) articles involved the use of magnetic resonance imaging (MRI). The proportion of published studies involving the use of MRI was higher than previous years. An increasing number of articles were also published on imaging of subjects with joint injury and on deep learning application in OA imaging. CONCLUSION: MRI and other imaging modalities continue to play an important role in research studies designed to better understand the pathogenesis, progression, and treatment of OA.

Are contrast-enhanced and non-contrast MRI findings reflecting synovial inflammation in knee osteoarthritis: a meta-analysis of observational studies.

OBJECTIVE: To determine the correlation between knee synovitis assessed on contrast-enhanced (CE) and non-contrast enhanced (NCE) magnetic resonance imaging (MRI) with histology in patients with knee osteoarthritis. METHODS: A comprehensive literature search was performed, and related articles published through July 2018 were extracted. Spearman correlation coefficients of MRI-based scores with histology reports were pooled using random effects model. To evaluate presence of publication bias, Egger test was performed. RESULTS: Of 2377 identified records, eight studies consisting of 246 MRI exams were included. Two studies reported results of dynamic CE (DCE)-MRI examinations (81 knees) and two studies reported results of NCE-MRI. There were moderate positive correlations between CE-MRI scores and macroscopic (r = 0.53 (95% Confidence Interval (CI):0.37-0.66), P < 0.001) as well as microscopic (r = 0.56 (0.39-0.69), P < 0.001) histology. DCE-MRI were strongly correlated (r = 0.71 (0.58-0.80), P-value<0.001), with microscopic histology reports, while the correlation for NCE-MRI was low positive (r = 0.44 (0.20-0.63), P < 0.001). Meta-regression analysis showed that pooled correlation coefficients of DCE-MRI were significantly higher than CE-MRI (Slope = 0.29, SE = 0.13, P-value = 0.02). CE-MRI were also correlated with inflammatory infiltrate (r = 0.42), while the correlations for cell number of synovial lining (r = 0.27) and level of fibrosis (r = 0.29, P < 0.001) were very low. CONCLUSION: Static and dynamic CE-MRI evaluation of knee synovitis were positively correlated with macroscopic and microscopic features of synovial membrane inflammation. Among the features of synovial tissue inflammation, CE-MRI scores correlated best with the inflammatory infiltrates of synovial tissue. Paucity of current evidence warrants further studies to assess performance of NCE-MRI on determining knee synovitis.

Coupled Active Shape Models for Automated Segmentation and Landmark Localization in High-Resolution CT of the Foot and Ankle.

PURPOSE: We develop an Active Shape Model (ASM) framework for automated bone segmentation and anatomical landmark localization in weight-bearing Cone-Beam CT (CBCT). To achieve a robust shape model fit in narrow joint spaces of the foot (0.5 - 1 mm), a new approach for incorporating proximity constraints in ASM (coupled ASM, cASM) is proposed. METHODS: In cASM, shape models of multiple adjacent foot bones are jointly fit to the CBCT volume. This coupling enables checking for proximity between the evolving shapes to avoid situations where a conventional single-bone ASM might erroneously fit to articular surfaces of neighbouring bones. We used 21 extremity CBCT scans of the weight-bearing foot to compare segmentation and landmark localization accuracy of ASM and cASM in leave-one-out validation. Each scan was used as a test image once; shape models of calcaneus, talus, navicular, and cuboid were built from manual surface segmentations of the remaining 20 scans. The models were augmented with seven anatomical landmarks used for common measurements of foot alignment. The landmarks were identified in the original CBCT volumes and mapped onto mean bone shape surfaces. ASM and cASM were run for 100 iterations, and the number of principal shape components was increased every 10 iterations. Automated landmark localization was achieved by applying known point correspondences between landmark vertices on the mean shape and vertices of the final active shape segmentation of the test image. RESULTS: Root Mean Squared (RMS) error of bone surface segmentation improved from 3.6 mm with conventional ASM to 2.7 mm with cASM. Furthermore, cASM achieved convergence (no change in RMS error with iteration) after ~40 iterations of shape fitting, compared to ~60 iterations for ASM. Distance error in landmark localization was 25% to 55% lower (depending on the landmark) with cASM than with ASM. The importance of using a coupled model is underscored by the finding that cASM detected and corrected collisions between evolving shapes in 50% to 80% (depending on the bone) of shape model fits. CONCLUSION: The proposed cASM framework improves accuracy of shape model fits, especially in complexes of tightly interlocking, articulated joints. The approach enables automated anatomical analysis in volumetric imaging of the foot and ankle, where narrow joint spaces challenge conventional shape models.

Tibiofibular syndesmosis in asymptomatic ankles: initial kinematic analysis using four-dimensional CT.

AIM: To evaluate the reliability of ankle syndesmotic measurements and their changes during active motion using four-dimensional computed tomography (4DCT) examination in asymptomatic ankles. MATERIALS AND METHODS: 4DCT was performed on both ankles of patients with signs and symptoms of unilateral ankle instability. Ankles from the asymptomatic side of 10 consecutive patients were included in this analysis. Five ankle syndesmotic measurements were adopted from the available literature and performed by two fellowship-trained foot and ankle surgeons: (1) syndesmotic anterior distance (SAD); (2) syndesmotic posterior distance (SPD); (3) syndesmotic translation (ST); (4) syndesmotic tibiofibular angle (STFA); and (5) ankle tibiofibular angle (ATFA). A Monte Carlo simulation was also performed to obtain exact p-values with 99% confidence intervals. RESULTS: Excellent interobserver reliability was observed among the two readers for four out of five measurements (intra-class correlation coefficients [ICC]: 0.767-0.995, p<0.001-0.020). The ICC values for SAD were not statistically significant (ICC=0.548 and 0.569 for dorsi and plantarflexion respectively, p=0.1). Among the five measurements, only ST measurements had significant changes during active motion (median [interquartile range] for change: -0.70 mm [-1.6-0.10]; p=0.012). Of the above measurements, only the ST measurements demonstrated a negative linear association with the tibiocalcaneal angle during active motion (beta=-2.5, p=0.04). CONCLUSIONS: Reliable quantitative kinematic assessment of ankle syndesmosis can be performed using 4DCT examination. Syndesmotic measurements remain unchanged during ankle motion except for the syndesmotic translation, which tends to decrease during plantar flexion.

Association of patella alta with worsening of patellofemoral osteoarthritis-related structural damage: data from the Osteoarthritis Initiative.

OBJECTIVES: To determine the association between Insall-Salvati ratio (ISR), a measure of patella alta, and worsening of Magnetic Resonance Imaging (MRI)-based osteoarthritis (OA)-related patellofemoral joint structural damages over 24-month in participants of the Osteoarthritis Initiative (OAI). DESIGN: Using weighted random sampling method, we selected a sample of 500 knees (from 1,677 knees with available baseline and 24-months MRI OA Knee Score (MOAKS) measurements), which is OAI-representative regarding knee OA-related factors (i.e., baseline age, sex, body mass index (BMI), and radiographic Kellgren-Lawrence grading). The ISR was measured in all enrolled knees using baseline sagittal 3T-MRI plane by three radiologists. Baseline and 24-month MOAKS variables for patellofemoral bone marrow lesions (BMLs), cartilage damages, and osteophytes were extracted, and the associations between ISR and 24-month worsening of these 3T-MRI features were evaluated using multivariable regression models. After computing receiver operating characteristic curves, the optimal cutoff point of ISR for indicating worsening of patellofemoral OA was determined. P-values were adjusted for multiple comparisons and false discovery rate (FDR) adjusted P-values were reported. RESULTS: In this longitudinal analysis, 24-month worsening of BML (odds ratio [OR] (95% confidence interval [95% CI]):11.18 (3.35-39.6), adjusted-p-value:<0.001) and cartilage scores (OR:7.39 (1.62-34.71), adjusted-p-value:0.042) in lateral patella was associated with higher baseline ISR. However, higher ISR was not statistically associated with medial patellar or medial and lateral trochlear BML or cartilage scores worsening. We determined the optimal cutoff point of ISR≥1.14 (95% CI: 1.083-1.284) for predicting lateral patellofemoral OA-related structural damages worsening over 24-months (sensitivity:73.73%; specificity: 66.67%). CONCLUSIONS: Given the uncertainly surrounding the results, our overall findings suggest that ISR could be considered as a predictor of lateral patellofemoral OA-related structural damages worsening with the optimal cutoff point of ≥1.14 using knee sagittal MRI measurements.

Osteoarthritis year in review 2017: updates on imaging advancements.

OBJECTIVE: This narrative review covers original research publications related to imaging advancements in osteoarthritis (OA) published in the English language between 1st April 2016 and 30th April 2017. METHODS: Relevant human studies (excluding pre-clinical and in vitro studies), were searched and selected from PubMed database using the search terms of "osteoarthritis (OA)" in combination with "radiography", "magnetic resonance imaging (MRI)", "computed tomography (CT)", "ultrasound", "positron emission tomography (PET)," "single-photon emission computed tomography (SPECT)," and "scintigraphy". The included studies were sorted according to their relevance, novelty, and impact. Original research articles with both imaging advancements and novel clinical information were discussed in this review. RESULTS: A large portion of the published studies were focused on MRI-based semi-quantitative and quantitative (morphological and structural) metrics of the knee joint to assess OA-related structural damages. New imaging technologies, such as PET, have been investigated for OA diagnosis and characterization, the delineation of predictive factors for OA progression, and to monitor the treatment responses. CONCLUSION: Advanced imaging modalities play a pivotal role in OA research, and make a significant contribution to our understanding of OA diagnosis, pathogenesis, risk stratification, and prognosis.

Bisphosphonates intake and its association with changes of periarticular bone area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: To determine the association between bisphosphonate treatment with the change of periarticular bone area and three-dimensional (3D) shape in participants of the Osteoarthritis Initiative (OAI) study. DESIGN: Using propensity score (PS) matching method in females, 48 bisphosphonate users and 105 non-users, who were matched for osteoarthritis (OA) and osteoporosis (OP) related factors were included. Baseline and 24-month magnetic resonance imaging (MRI)-based periarticular bone area and 3D shape measurements were used. The association between bisphosphonate intake and 24-month interval changes of the periarticular bone area and 3D shape were evaluated using paired Wilcoxon signed rank test. We used conditional logistic regression models for determining the association between bisphosphonate intake and periarticular bone change, defined using the standard deviation of difference (SDD) and reliable change index (RCI) methods. P-values have been adjusted for multiple comparisons using Benjamini & Hochberg procedure and false discovery rate (FDR)-adjusted P-values were reported. RESULTS: The 24-month interval increases in the periarticular bone area in medial side of tibia were significantly greater in non-users than users (FDR-adjusted P-value: 0.002). There was an approaching significance trend for lower medial tibial periarticular bone area expansion in bisphosphonate users in comparison with non-users (For 1SDD change, odds ratio 95% confidence interval (OR (95% CI)): 0.514 (0.271-0.975), FDR-adjusted P-value: 0.085) (For 1.96RCI change, OR (95% CI): 0.552 (0.309-0.986), FDR-adjusted P-value: 0.085). CONCLUSIONS: Bisphosphonate intake was associated with a reduction in the odds (approaching but not achieving significance) of expansion periarticular bone area, specifically in the medial tibial sub-region.

Robust Quantitative Assessment of Trabecular Microarchitecture in Extremity Cone-Beam CT Using Optimized Segmentation Algorithms.

PURPOSE: In-vivo evaluation of bone microarchitecture remains challenging because of limited resolution of conventional orthopaedic imaging modalities. We investigate the performance of flat-panel detector extremity Cone-Beam CT (CBCT) in quantitative analysis of trabecular bone. To enable accurate morphometry of fine trabecular bone architecture, advanced CBCT pre-processing and segmentation algorithms are developed. METHODS: The study involved 35 transilliac bone biopsy samples imaged on extremity CBCT (voxel size 75 µm, imaging dose ~13 mGy) and gold standard µCT (voxel size 7.67 µm). CBCT image segmentation was performed using (i) global Otsu's thresholding, (ii) Bernsen's local thresholding, (iii) Bernsen's local thresholding with additional histogram-based global pre-thresholding, and (iv) the same as (iii) but combined with contrast enhancement using a Laplacian Pyramid. Correlations between extremity CBCT with the different segmentation algorithms and gold standard µCT were investigated for measurements of Bone Volume over Total Volume (BV/TV), Trabecular Thickness (Tb.Th), Trabecular Spacing (Tb.Sp), and Trabecular Number (Tb.N). RESULTS: The combination of local thresholding with global pre-thresholding and Laplacian contrast enhancement outperformed other CBCT segmentation methods. Using this optimal segmentation scheme, strong correlation between extremity CBCT and µCT was achieved, with Pearson coefficients of 0.93 for BV/TV, 0.89 for Tb.Th, 0.91 for Tb.Sp, and 0.88 for Tb.N (all results statistically significant). Compared to a simple global CBCT segmentation using Otsu's algorithm, the advanced segmentation method achieved ~20% improvement in the correlation coefficient for Tb.Th and ~50% improvement for Tb.Sp. CONCLUSIONS: Extremity CBCT combined with advanced image pre-processing and segmentation achieves high correlation with gold standard µCT in measurements of trabecular microstructure. This motivates ongoing development of clinical applications of extremity CBCT in in-vivo evaluation of bone health e.g. in early osteoarthritis and osteoporosis.

Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients.

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.

Role of physical activity in cartilage damage progression of subjects with baseline full-thickness cartilage defects in medial tibiofemoral compartment: data from the Osteoarthritis Initiative.

OBJECTIVE: To assess the association between physical activity and cartilage damage progression in medial tibiofemoral compartment (MTFC) using 2-year follow-up magnetic resonance imaging (MRI) in subjects with denuded areas of subchondral bone (dABs) at the central weight-bearing medial femur (cMF) at baseline MRI examination. METHODS: One hundred subjects from the Osteoarthritis Initiative (OAI) progression cohort with dABs at the cMF at 3T MRI at baseline (51% men; mean age 62.2 years, range 45-79) were included. Sagittal 3D dual-echo steady-state with water excitation images were used to assess 2-year MTFC cartilage change. Associations between 2-year average Physical Activity Scale for the Elderly (PASE) and 2-year MTFC cartilage change were assessed by linear regression analysis. Subgroup analyses were performed. RESULTS: No associations between PASE and 2-year MTFC cartilage change were observed in the entire cohort. Similarly, in the subgroup with cartilage loss during the 2 years, the non-refuted confidence intervals for the regression coefficients were tightly clustered around the null value (regression coefficients for: mean cMF.ThCtAB = -0.00059; 98.75% CI: -0.00130 to 0.00012), cMF.dAB% = 0.02176; 98.75% CI: -0.02514 to 0.06865, Mean MT.ThCtAB = -0.00013; 98.75% CI: -0.00064 to 0.00038, MT.dAB% = 0.02543; 98.75% CI: -0.01485 to 0.06571. CONCLUSION: In the entire group of subjects with dABs at the cMF at baseline, no association between physical activity and 2-year MTFC cartilage change was detected. Due to the limited sample size of our study, small-sized effects may not have been detected in our study.

Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative.

OBJECTIVES: To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). DESIGN: Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic +) and 173 referent (Analgesic -) subjects were included. Analgesic + and - subjects had analgesics in all and none of their visits, respectively. Analgesic + and - subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic + and - subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. RESULTS: Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic + and 15 among Analgesic - subjects (P = 0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic + and 12 among Analgesic - subjects (P = 0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic + subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. CONCLUSIONS: Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR.