Soft drink intake and progression of radiographic knee osteoarthritis: data from the osteoarthritis initiative

Objectives: We examine the prospective association of soft drink consumption with radiographic progression of knee osteoarthritis (OA). Design: Prospective cohort study. Setting: This study used data from the osteoarthritis initiative (OAI). Participants: In OAI, 2149 participants with radiographic knee OA and having dietary data at baseline were followed up to 12, 24, 36 and 48 months. Measures The soft drink consumption was assessed with a Block Brief Food Frequency Questionnaire completed at baseline. To evaluate knee OA progression, we used quantitative medial tibiofemoral joint space width (JSW) based on plain radiographs. The multivariate linear models for repeated measures were used to test the independent association between soft drink intake and the change in JSW over time, while adjusting for body mass index and other potential confounding factors. Results: In stratified analyses by gender, we observed a significant dose–response relationship between baseline soft drink intake and adjusted mean change of JSW in men. With increasing levels of soft drink intake (none, ≤1, 2–4 and ≥5 times/week), the mean decreases of JSW were 0.31, 0.39, 0.34 and 0.60 mm, respectively. When we further stratified by obesity, a stronger dose–response relationship was found in non-obese men. In obese men, only the highest soft drink level (≥5 times/week) was associated with increased change in JSW compared with no use. In women, no significant association was observed. Conclusions: Our results suggest that frequent consumption of soft drinks may be associated with increased OA progression in men. Replication of these novel findings in other studies demonstrating the reduction in soft drink consumption leads to delay in OA progression is needed

Minimum joint space width and tibial cartilage morphology in the knees of healthy individuals: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The clinical use of minimum joint space width (mJSW) and cartilage volume and thickness has been limited to the longitudinal measurement of disease progression (i.e. change over time) rather than the diagnosis of OA in which values are compared to a standard. This is primarily due to lack of establishment of normative values of joint space width and cartilage morphometry as has been done with bone density values in diagnosing osteoporosis. Thus, the purpose of this pilot study is to estimate reference values of medial joint space width and cartilage morphometry in healthy individuals of all ages using standard radiography and peripheral magnetic resonance imaging.</p> <p>Design</p> <p>For this cross-sectional study, healthy volunteers underwent a fixed-flexion knee X-ray and a peripheral MR (pMR) scan of the same knee using a 1T machine (ONI OrthOne™, Wilmington, MA). Radiographs were digitized and analyzed for medial mJSW using an automated algorithm. Only knees scoring ≤1 on the Kellgren-Lawrence scale (no radiographic evidence of knee OA) were included in the analyses. All 3D SPGRE fat-sat sagittal pMR scans were analyzed for medial tibial cartilage morphometry using a proprietary software program (Chondrometrics GmbH).</p> <p>Results</p> <p>Of 119 healthy participants, 73 were female and 47 were male; mean (SD) age 38.2 (13.2) years, mean BMI 25.0 (4.4) kg/m². Minimum JSW values were calculated for each sex and decade of life. Analyses revealed mJSW did not significantly decrease with increasing decade (p > 0.05) in either sex. Females had a mean (SD) medial mJSW of 4.8 (0.7) mm compared to males with corresponding larger value of 5.7 (0.8) mm. Cartilage morphometry results showed similar trends with mean (SD) tibial cartilage volume and thickness in females of 1.50 (0.19) μL/mm²and 1.45 (0.19) mm, respectively, and 1.77 (0.24) μL/mm²and 1.71 (0.24) mm, respectively, in males.</p> <p>Conclusion</p> <p>These data suggest that medial mJSW values do not decrease with aging in healthy individuals but remain fairly constant throughout the lifespan with "healthy" values of 4.8 mm for females and 5.7 mm for males. Similar trends were seen for cartilage morphology. Results suggest there may be no need to differentiate a t-score and a z-score in OA diagnosis because cartilage thickness and JSW remain constant throughout life in the absence of OA.</p

Pancreatic cancer epigenetics: adaptive metabolism reprograms starving primary tumors for widespread metastatic outgrowth

Pancreatic cancer is a paradigm for adaptation to extreme stress. That is because genetic drivers are selected during tissue injury with epigenetic imprints encoding wound healing responses. Ironically, epigenetic memories of trauma that facilitate neoplasia can also recreate past stresses to restrain malignant progression through symbiotic tumor:stroma crosstalk. This is best exemplified by positive feedback between neoplastic chromatin outputs and fibroinflammatory stromal cues that encase malignant glands within a nutrient-deprived desmoplastic stroma. Because epigenetic imprints are chemically encoded by nutrient-derived metabolites bonded to chromatin, primary tumor metabolism adapts to preserve malignant epigenetic fidelity during starvation. Despite these adaptations, stromal stresses inevitably awaken primordial drives to seek more hospitable climates. The invasive migrations that ensue facilitate entry into the metastatic cascade. Metastatic routes present nutrient-replete reservoirs that accelerate malignant progression through adaptive metaboloepigenetics. This is best exemplified by positive feedback between biosynthetic enzymes and nutrient transporters that saturate malignant chromatin with pro-metastatic metabolite byproducts. Here we present a contemporary view of pancreatic cancer epigenetics: selection of neoplastic chromatin under fibroinflammatory pressures, preservation of malignant chromatin during starvation stresses, and saturation of metastatic chromatin by nutritional excesses that fuel lethal metastasis

Brief Report: Development and Validation of a Semiautomated Method to Measure Erosion Volume in Inflammatory Arthritis by Computed Tomography Scanning

OBJECTIVE: Valid measurement of erosion volume in rheumatoid arthritis (RA) will facilitate the testing of treatments that may help to heal erosion. This study was undertaken to develop and validate a software method to measure erosion volume on computed tomography (CT) scans of the hand and wrist. METHODS: Duplicate CT acquisitions of both hands of 5 patients with RA were evaluated using a semiautomated software tool to measure erosion volume in the entire hand and wrist and in each of 6 subregions. Reproducibility was quantified using the intraclass correlation coefficient (ICC), root mean square standard deviation (RMSSD), and coefficient of variation (CV), and the analysis was performed at the level of the hand (n = 10) and the subject (n = 5). RESULTS: The ICCs between 2 repositioned acquisitions were excellent, ranging from 0.97 to 1.00. At the hand level, the RMSSD was 15.6 mm(3) with a CV of 7.3%, and the CVs at the 6 regions ranged from 7.6% to 21.0%. At the subject level, the RMSSD was 31.2 mm(3) with a CV of 3.7%, and the CVs at the 6 regions ranged from 0.5% to 15.8%. CONCLUSION: We have developed a novel semiautomated software method to measure erosion volume on hand and wrist CT scans. The method is reproducible and can be used to detect changes in erosion volume. This will facilitate the testing of treatments intended to reduce erosion volume

Comparison of 2 Radiographic Techniques for Measurement of Tibiofemoral Joint Space Width

Background: No consensus is available regarding the best method for measuring tibiofemoral joint space width (JSW) on radiographs to quantify joint changes after injury. Studies that track articular cartilage thickness after injury frequently use patients’ uninjured contralateral knees as controls, although the literature supporting this comparison is limited. Purpose: (1) To compare JSW measurements using 2 established measurement techniques in healthy control participants and (2) to determine whether the mean JSW of the uninjured contralateral knee in a cohort with anterior cruciate ligament (ACL) reconstruction is different from that obtained from a true control population. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Medial and lateral JSWs were measured on standardized, bilateral, semiflexed metatarsophalangeal positioning, posteroanterior radiographs of 60 healthy individuals (26 females; mean ± SD age, 25 ± 6.2 years; no history of knee injury) via 2 published techniques: a computerized surface-delineation method (surface-fit method) and a manual digitization method (midpoint method). Bland-Altman method was used to examine the agreement between JSW measurements obtained with the 2 methods and to examine the agreement between measurements obtained on left and right knees within a participant for each measurement method. Within- and between-participant variance components and intraclass correlation coefficients (ICCs) were computed for JSW measurements corresponding to each method. Two-sample t tests were used to compare the surface-fit method measurements of mean JSW of the true control group (n = 60) with the previously published mean JSW measurements from the Multicenter Orthopaedics Outcomes Network (MOON) nested cohort of 262 contralateral uninjured knees 2 to 3 years after ACL reconstruction. Results: For JSW in the medial compartment, the surface-fit method had lower within-participant interknee variability (σ2 within, 0.064; 95% CI, 0.04-0.09) compared with the midpoint method (σ2 within, 0.28; 95% CI, 0.20-0.43) and a higher ICC (0.93 vs 0.65; P < .001). Lateral JSW values were similar for the surface-fit method (σ2 within, 0.27; 95% CI, 0.18-0.43) and the midpoint method (σ2 within, 0.20; 95% CI, 0.14-0.31), with ICCs of 0.75 and 0.77, respectively (P = .80). With the surface-fit method, mean JSW measurements of the medial and lateral compartments of a control population were not significantly different from the contralateral uninjured knees of patients after ACL reconstruction. Conclusion: For measuring medial JSW, the surface-fit method was less variable across knees within a participant than the midpoint method, as evidenced by larger ICCs and lower interknee variability. For measuring lateral JSW, the 2 methods were similar. The JSW measurements of uninjured contralateral knees of patients with ACL reconstruction at 2 to 3 years postsurgery were not significantly different from those of a cohort of healthy control participants. Future work should be performed to demonstrate the validity of these methods for documenting change over time in the ACL-reconstructed knee

Coronal tibial slope is associated with accelerated knee osteoarthritis: data from the Osteoarthritis Initiative

Background: Accelerated knee osteoarthritis may be a unique subset of knee osteoarthritis, which is associated with greater knee pain and disability. Identifying risk factors for accelerated knee osteoarthritis is vital to recognizing people who will develop accelerated knee osteoarthritis and initiating early interventions. The geometry of an articular surface (e.g., coronal tibial slope), which is a determinant of altered joint biomechanics, may be an important risk factor for incident accelerated knee osteoarthritis. We aimed to determine if baseline coronal tibial slope is associated with incident accelerated knee osteoarthritis or common knee osteoarthritis. Methods: We conducted a case–control study using data and images from baseline and the first 4 years of follow-up in the Osteoarthritis Initiative. We included three groups: 1) individuals with incident accelerated knee osteoarthritis, 2) individuals with common knee osteoarthritis progression, and 3) a control group with no knee osteoarthritis at any time. We did 1:1:1 matching for the 3 groups based on sex. Weight-bearing, fixed flexion posterior-anterior knee radiographs were obtained at each visit. One reader manually measured baseline coronal tibial slope on the radiographs. Baseline femorotibial angle was measured on the radiographs using a semi-automated program. To assess the relationship between slope (predictor) and incident accelerated knee osteoarthritis or common knee osteoarthritis (outcomes) compared with no knee osteoarthritis (reference outcome), we performed multinomial logistic regression analyses adjusted for sex. Results: The mean baseline slope for incident accelerated knee osteoarthritis, common knee osteoarthritis, and no knee osteoarthritis were 3.1(2.0), 2.7(2.1), and 2.6(1.9); respectively. A greater slope was associated with an increased risk of incident accelerated knee osteoarthritis (OR = 1.15 per degree, 95 % CI = 1.01 to 1.32) but not common knee osteoarthritis (OR = 1.04, 95 % CI = 0.91 to 1.19). These findings were similar when adjusted for recent injury. Among knees with varus malalignment a greater slope increases the odds of incident accelerated knee osteoarthritis; there is no significant relationship between slope and incident accelerated knee osteoarthritis among knees with normal alignment. Conclusions: Coronal tibial slope, particularly among knees with malalignment, may be an important risk factor for incident accelerated knee osteoarthritis

Reliability and Validity of Single Axial Slice vs. Multiple Slice Quantitative Measurement of the Volume of Effusion-Synovitis on 3T Knee MRI in Knees with Osteoarthritis

Effusion-synovitis (ES) is recognized as a component of osteoarthritis, creating a need for rapid methods to assess ES on MRI. We describe the development and reliability of an efficient single-slice semi-automated quantitative approach to measure ES. We used two samples from the Osteoarthritis Initiative (OAI): 50 randomly selected OAI participants with radiographic osteoarthritis (i.e., Kellgren–Lawrence (KL) grade 2 or 3) and a subset from the Foundation for the National Institutes of Health Osteoarthritis Biomarker study. An experienced musculoskeletal radiologist trained four non-expert readers to use custom semi-automated software to measure ES on a single axial slice and then read scans blinded to prior assessments. The estimated intraclass correlation coefficient (ICC) for intra-reader reliability of the single-slice ES method in the KL 2–3 sample was 0.96 (95% CI: 0.93, 0.97), and for inter-reader reliability, the ICC was 0.90 (95% CI: 0.87, 0.95). The intra-reader mean absolute difference (MAD) was 35 mm3 (95% CI: 28, 44), and the inter-reader MAD was 61 mm3 (95% CI: 48, 76). Our single-slice quantitative knee ES measurement offers a reliable, valid, and efficient surrogate for multi-slice quantitative and semi-quantitative assessment

Bone Structure Analysis of the Radius Using Ultrahigh Field (7T) MRI: Relevance of Technical Parameters and Comparison with 3T MRI and Radiography.

Bone fractal signature analysis (FSA-also termed bone texture analysis) is a tool that assesses structural changes that may relate to clinical outcomes and functions. Our aim was to compare bone texture analysis of the distal radius in patients and volunteers using radiography and 3T and 7T magnetic resonance imaging (MRI)-a patient group (n = 25) and a volunteer group (n = 25) were included. Participants in the patient group had a history of chronic wrist pain with suspected or confirmed osteoarthritis and/or ligament instability. All participants had 3T and 7T MRI including T1-weighted turbo spin echo (TSE) sequences. The 7T MRI examination included an additional high-resolution (HR) T1 TSE sequence. Radiographs of the wrist were acquired for the patient group. When comparing patients and volunteers (unadjusted for gender and age), we found a statistically significant difference of horizontal and vertical fractal dimensions (FDs) using 7T T1 TSE-HR images in low-resolution mode (horizontal: p = 0.04, vertical: p = 0.01). When comparing radiography to the different MRI sequences, we found a statistically significant difference for low- and high-resolution horizontal FDs between radiography and 3T T1 TSE and 7T T1 TSE-HR. Vertical FDs were significantly different only between radiographs and 3T T1 TSE in the high-resolution mode; FSA measures obtained from 3T and 7T MRI are highly dependent on the sequence and reconstruction resolution used, and thus are not easily comparable between MRI systems and applied sequences

Role of Magnetic Resonance Imaging in Classifying Individuals Who Will Develop Accelerated Radiographic Knee Osteoarthritis.

We assessed whether adding magnetic resonance (MR)-based features to a base model of clinically accessible participant characteristics (i.e., serological, radiographic, demographic, symptoms, and physical function) improved classification of adults who developed accelerated radiographic knee osteoarthritis (AKOA) or not over the subsequent 4 years. We conducted a case-control study using radiographs from baseline and the first four annual visits of the osteoarthritis initiative to define groups. Eligible individuals had no radiographic KOA in either knee at baseline (Kellgren-Lawrence [KL] grade <2). We classified two groups matched on sex (i) AKOA: at least one knee developed advanced-stage KOA (KL = 3 or 4) within 48 months and (ii) did not develop AKOA within 48 months. The MR-based features were assessments of bone, effusion/synovitis, tendons, ligaments, cartilage, and menisci. All characteristics and MR-based features were from the baseline visit. Classification and regression tree analyses were performed to determine classification rules and identify statistically important variables. The CART models with and without MR features each explained approximately 40% of the variability. Adding MR-based features to the model yielded modest improvements in specificity (0.90 vs. 0.82) but lower sensitivity (0.62 vs. 0.70) than the base model. There was consistent evidence that serum glucose, effusion-synovitis volume, and cruciate ligament degeneration are statistically important variables in classifying individuals who will develop AKOA. We found common MR-based measures failed to dramatically improve classification. These findings also show a complex interplay among participant characteristics and a need to identify novel characteristics to improve classification. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2420-2428, 2019