Machine learning to predict incident radiographic knee osteoarthritis over 8 Years using combined MR imaging features, demographics, and clinical factors: data from the Osteoarthritis Initiative.

OBJECTIVE: To develop a machine learning-based prediction model for incident radiographic osteoarthritis (OA) of the knee over 8 years using MRI-based cartilage biochemical composition and knee joint structure, demographics, and clinical predictors including muscle strength and symptoms. DESIGN: Individuals (n = 1,044) with baseline Kellgren Lawrence (KL) grade 0-1 in the right knee from the Osteoarthritis Initiative database were analyzed. 3T MRI at baseline was used to quantify knee cartilage T2, and Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone marrow. The outcome was set as true if a subject developed KL grade 2-4 OA in the right knee over 8 years (n = 183) and false if the subject remained at KL 0-1 over 8 years (n = 861). We developed and compared three models: Model 1: 112 predictors based on OA risk factors; Model 2: top ten predictors based on feature importance score from Model 1 and clinical relevance; Model 3: Model 2 without the imaging predictors. We compared the models using the area under the ROC curve derived from hold-out data. RESULTS: The 10-predictor model (Model 2, that includes cartilage and meniscus WORMS scores and cartilage T2) had a slightly lower AUC (0.772) compared to the model with 112 predictors (Model 1: AUC = 0.792, p = 0.739); and had a significantly higher AUC compared to the model without MR imaging predictors (Model 3, AUC = 0.669, p = 0.011). CONCLUSIONS: A 10-predictor model including MRI parameters coupled with demographics, symptoms, muscle, and physical activity scores provides good prediction of incident radiographic OA over 8 years.

Anterior cruciate ligament abnormalities are associated with accelerated progression of knee joint degeneration in knees with and without structural knee joint abnormalities: 96-month data from the Osteoarthritis Initiative.

OBJECTIVE: To compare progression over 8 years in knee compositional cartilage degeneration and structural joint abnormalities in knees with different types of anterior cruciate ligament (ACL) abnormalities over 8 years. METHOD: Baseline MR images of the right knees of 1899 individuals of the Osteoarthritis Initiative (OAI) with no evidence of or mild to moderate radiographic osteoarthritis were assessed for nontraumatic ACL abnormalities. The knees of 91 individuals showed nontraumatic ACL abnormalities (age 60.6 ± 9.8 y, 46 females; mucoid degeneration (MD), N = 37; complete tear (CT), N = 22; partial tear (PT), N = 32) and were frequency-matched to 91 individuals with normal ACL. MRIs were assessed for knee joint abnormalities using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and cartilage T2 mapping at baseline, 4- and 8-year follow-up. RESULTS: Over 8 years, cartilage T2 values of the medial tibia showed a significantly greater increase in individuals with MD, PT or CT compared to those with normal ACL (adjusted rate of change/year [95% confidence interval], normal ACL: 0.06 [0.01, 0.23], MD: 0.34 [0.07, 0.73], PT, 0.21 [0.02, 0.33], CT, 0.51 [0.16, 0.78]), indicating an association of ACL abnormalities and an increased progression rate of cartilage degeneration in subjects with and without knee joint degeneration. This effect was also seen in cartilage T2 values averaged over all compartments (normal ACL: 0.08 [0.05, 0.20] vs abnormal ACL: 0.27 [0.06, 0.56]). CONCLUSIONS: Over 8 years, higher progression rates of cartilage degeneration, especially in the medial tibia, were associated with ACL abnormalities compared to those with normal ACL, in subjects with and without knee joint abnormalities.

Identification of non-Hodgkin lymphoma patients at risk for treatment-related vertebral density loss and fractures.

Information on bone loss in treated non-Hodgkin's lymphoma patients is limited. In this study, we used CT to analyze bone loss as well as prevalent and incident fractures. We found severe bone loss, a high rate of fractures, and a novel association between bone loss and the international prognostic index. INTRODUCTION: To investigate bone loss and fracture risk in non-Hodgkin-lymphoma (NHL) patients by (i) comparing treatment-related vertebral density (VD) loss in NHL patients with control subjects and (ii) investigating associations of VD loss versus fracture risk. Further, associations of VD loss and clinical parameters were investigated. METHODS: VD of 123 NHL patients was measured pre- and post-treatment in the L1, L2, and L3 vertebrae in routine computed tomography (CT) scans, performed between Jan 2016 and Mar 2017. Control measurements (n = 52) were obtained from CT colonographies between Sept 2003 and Sept 2017 and their subsequent follow-up-exams (10-137 months). Prevalent and incident (between baseline and follow-up) fractures were assessed in all subjects, and VD loss per year was calculated. Linear regression models were used to (i) compare VD loss between patients and controls and (ii) identify associations between VD loss and clinical parameters. Using logistic regression models, ORs for fractures per SD change in VD were assessed in patients. Analyses were adjusted for age, sex, and contrast application. RESULTS: NHL patients experienced significantly greater VDL1-3 loss than controls (P = 0.003), and greater VDL1-3 loss was associated with a greater likelihood of incident fractures (OR, [95%-CI], P 1.90, [1.03, 3.51], 0.04). Patients with an initial international prognostic index (IPI) of 5 suffered significantly greater VD loss compared with an IPI of 0 (P = 0.01). CONCLUSION: Using VD measurements in routine CT scans, substantial vertebral bone loss in NHL patients could be documented with a high incidence of fractures.

Impact of different physical activity types on knee joint structural degeneration assessed with 3-T MRI in overweight and obese subjects: data from the osteoarthritis initiative.

OBJECTIVE: To assess the impact of different types of physical activity types on longitudinal knee joint structural changes over 48 months in overweight and obese subjects. MATERIALS AND METHODS: We included 415 subjects with a BMI ≥ 25 kg/m2, Kellgren-Lawrence scores ≤ 3 at baseline and Whole-Organ Magnetic Resonance Imaging Score (WORMS) scores available from the Osteoarthritis Initiative cohort. Regular self-reported participation in six physical activity types was assessed: ball sports, bicycling, jogging/running, elliptical-trainer, racquet sports, and swimming. Moreover, they were classified into high- and low-impact physical activity groups. Evaluation of structural knee abnormalities was performed using WORMS obtained by two independent observers blinded to the subjects' physical activity and time point. Linear regression models were used to assess the associations between participation in different physical activity types and changes in WORMS. RESULTS: No significant differences in epidemiological data were found between the groups except for gender composition, and there were no significant differences in baseline WORMS. In the cohort as a whole and most exercise groups overall WORMS significantly increased during the observational period. Highest increases compared to the remainder of the group were found in the high impact group (increase in WORMS 4.65; [95% CI] [3.94,5.35]; p = 0.040) and the racquet sports group (6.39; [95% CI] [5.13,7.60]; p ≤ 0.001). Subjects using an elliptical-trainer showed the lowest increase in WORMS (- 1.50 [- 0.21, 3.22]; p = 0.002). CONCLUSION: Progression of knee joint degeneration was consistently higher in subjects engaging in high-impact and racquet sports while subjects using an elliptical-trainer showed the smallest changes in structural degeneration. This work was presented during the 2020 Radiological Society of North America Annual meeting.

Chondrocalcinosis is associated with increased knee joint degeneration over 4 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine if presence of calcium-containing crystals (CaC) is associated with increased knee joint degeneration over 4 years and assess if total number of CaCs deposited is a useful measure of disease burden. DESIGN: Seventy subjects with CaCs in right knees at baseline were selected from the Osteoarthritis Initiative and matched to 70 subjects without evidence of CaCs. T1-weighted gradient-echo sequences were used to confirm presence of CaCs and count the numbers of distinct circumscribed CaCs. Morphological abnormalities were assessed at baseline and 4-year follow-up using the modified semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression models were used to analyze the associations between presence of CaCs at baseline and changes in WORMS and to analyze the associations between numbers of circumscribed CaCs at baseline and changes in WORMS. RESULTS: Presence of CaCs was associated with increased cartilage degeneration in the patella (coefficient: 0.33; 95% confidence interval (CI): 0.04-0.63), the medial femur (coefficient: 0.51; 95% CI: 0.18-0.83), the lateral tibia (coefficient: 0.36; 95% CI: 0.01-0.71) as well as the medial and lateral meniscus (coefficient: 0.38; 95% CI: 0.00-0.75 and coefficient: 0.72; 95% CI: 0.12-1.32). Knees with higher numbers of CaCs had increased cartilage degeneration in the patella and medial femur (coefficient: 0.09; 95% CI: 0.05-0.14; P < 0.001 and coefficient: 0.08; 95% CI: 0.02-0.14; P = 0.005). CONCLUSIONS: CaCs were associated with increased cartilage and meniscus degeneration over a period of 4 years. Assessing the number of CaC depositions may be useful to evaluate risk of onset and worsening of degenerative disease.

Spatial distribution and temporal progression of T2 relaxation time values in knee cartilage prior to the onset of cartilage lesions - data from the Osteoarthritis Initiative (OAI).

PURPOSE: To investigate compositional changes of knee cartilage at the site of newly appearing cartilage lesions and the surrounding cartilage 1-4 years prior to lesion onset using quantitative T2-measurements. METHODS: Fifty-seven cartilage plates with newly appearing cartilage lesions from 45 knees (cases) and 52 plates from 26 control knees from the Osteoarthritis Initiative (OAI) cohort (controls) were evaluated. Using MRI T2-mapping, composition of local (the site of future lesions) and surrounding cartilage (remainder of the cartilage plate) was assessed 1-4 years prior to lesion onset. Analogous cartilage ROIs in control plates without cartilage lesions were assessed over 1-4 years. Mixed models were used to compare T2-means and change rates between local and surrounding cartilage within cases and controls, and to compare change rates in local and surrounding cartilage between cases and controls, adjusting for covariates. RESULTS: Four years prior to lesion onset, we found that local cartilage ROIs had higher T2-values compared to the surrounding cartilage. No such differences were found in control plates. In cases mean local T2-values were persistantly elevated compared to the surrounding cartilage prior to lesion onset reaching significance 1 year prior (+2.94 ms, p = 0.012). T2-values of the surrounding cartilage were also persistantly higher in cases compared to controls, reaching significance 2 years prior to lesion onset (+3.61 ms, p = 0.003). CONCLUSION: The findings of our study support the concept of compositional cartilage changes as a mechanism for cartilage degradation and that both diffuse and focal changes of cartilage composition within a cartilage plate precede the development of cartilage lesions.

Weight loss regimen in obese and overweight individuals is associated with reduced cartilage degeneration: 96-month data from the Osteoarthritis Initiative.

PURPOSE: To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss (WL), and to assess how different WL regimens are associated with these changes. METHODS: We studied right knees of 760 participants (age 62.6 ± 9.0y; 465 females) with a baseline body mass index (BMI) >25 kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N = 380) were compared to controls with stable weight (SW, N = 380). Participants losing weight were categorized based on WL method (diet and exercise, diet only, exercise only) and compared to those with stable weight. Magnetic resonance imaging (MRI) at 3T was performed at baseline, 48- and 96-months. The association of WL and WL method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models. RESULTS: Compared to SW, WL was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 (adjusted mean difference of change in T2 ms/year [95% CI] between the groups: 0.24 [0.20, 0.41] ms/year; P < 0.001) and global deep layer cartilage T2 0.35 [0.20, 0.42] ms/year; P < 0.001), suggesting slower cartilage deterioration. Compared to the SW group, slower increases in global T2 were observed in the diet and diet and exercise groups, but not in the exercise only group (P = 0.042, P = 0.003 and P = 0.85, respectively). CONCLUSION: Our results suggest that WL may slow knee cartilage degeneration over 96 months, and that these potential benefits may differ by method of WL.

Longitudinal changes in MR T1ρ/T2 signal of meniscus and its association with cartilage T1p/T2 in ACL-injured patients.

OBJECTIVE: To evaluate the longitudinal changes in meniscal T1ρ/T2 signal post-reconstruction in patients with acute anterior cruciate ligament (ACL) injury and to investigate the association with T1ρ/T2 signal in articular knee cartilage. METHOD: In this prospective study, knees of 37 patients with ACL-injury and reconstruction in addition to 13 healthy controls were scanned using magnetic resonance imaging (MRI) T1ρ/T2 mapping. Quantitative analysis of the meniscus was performed in the anterior/posterior horns of lateral/medial meniscus fourteen sub-compartments of cartilage spanning the medial/lateral area of the tibia and femoral condyles. Meniscus T1ρ/T2 signals were compared between injured, contralateral and control knees at baseline, 6-months, 1-year and 2-years using t-tests for cross-sectional comparisons and a mixed model for longitudinal comparisons. Pearson-partial correlations between meniscal and cartilage T1ρ/T2 were evaluated. RESULTS: There was a significant decrease of T1ρ/T2 signal in the posterior horn of lateral meniscus (PHLAT) of injured knees during a 2-year period. In the posterior horn of medial meniscus (PHMED), T1ρ/T2 signal of injured knees was significantly elevated at all time points post-reconstruction compared to contralateral and control knees. Within injured knees, PHMED T1ρ/T2 signal showed significant positive correlations with medial tibia (MT) cartilage T1ρ/T2 signal at all time points. CONCLUSION: A significant decrease in PHLAT T1ρ/T2 signal by 2-years suggests potential tissue recovery after ACL-injury. Elevated T1ρ/T2 signal in the PHMED of injured knees at 2-years correlating with knee cartilage T1ρ/T2 signal elevations suggests involvement of the PHMED in subacute cartilage degeneration after ACL-injury and reconstruction.

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

OBJECTIVE: The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN: 141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS: Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS: This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

Type 2 diabetes patients have accelerated cartilage matrix degeneration compared to diabetes free controls: data from the Osteoarthritis Initiative.

PURPOSE: Osteoarthritis (OA) and diabetes mellitus (DM) share common risk factors with a potential underlying relationship between both diseases. The purpose of this study was to investigate the longitudinal effects of DM on cartilage deterioration over 24-months with MR-based T2 relaxation time measurements. METHODS: From the Osteoarthritis Initiative (OAI) cohort 196 diabetics were matched in small sets for age, sex, BMI and Kellgren-Lawrence score with 196 non-diabetic controls. Knee cartilage semi-automatic segmentation was performed on 2D multi-slice multi-echo spin-echo sequences. Texture of cartilage T2 maps was obtained via grey level co-occurrence matrix analysis. Linear regression analysis was used to compare cross-sectional and changes in T2 and texture parameters between the groups. RESULTS: Both study groups were similar in age (63.3 vs 63.0 years, P = 0.70), BMI (30.9 vs 31.2 kg/m2, P = 0.52), sex (female 53.6% vs 54.1%, P = 0.92) and KL score distribution (P = 0.97). In diabetics, except for the patella, all compartments showed a significantly higher increase in mean T2 values when compared to non-diabetic controls. Global T2 values increased almost twice as much; 1.77ms vs 0.98ms (0.79ms [CI: 0.39,1.19]) (P < 0.001). Additionally, global T2 values showed a significantly higher increase in the bone layer (P = 0.006), and in a separate analysis of the texture parameters, diabetics also showed consistently higher texture values (P < 0.05), indicating a more disordered cartilage composition. CONCLUSION: Cartilage T2 values in diabetics show a faster increase with a consistently more heterogeneous cartilage texture composition. DM seems to be a risk factor for developing early OA with an accelerated degeneration of the articular cartilage in the knee.

Role of thigh muscle cross-sectional area and strength in progression of knee cartilage degeneration over 48 months - data from the Osteoarthritis Initiative.

OBJECTIVE: To determine in a 48-month longitudinal study the association of thigh muscle cross-sectional area (CSA) and strength on progression of morphologic knee cartilage degeneration using 3T magnetic resonance imaging (MRI). DESIGN: Seventy Osteoarthritis Initiative (OAI) subjects aged 50-60 years, with no radiographic evidence of osteoarthritis (OA) and constant muscle strength over 48 months as measured by isometric knee extension testing were included. Baseline right thigh muscle CSAs were assessed on axial T1-weighted magnetic resonance (MR) images, and extensor to flexor CSA ratios were calculated. Degenerative knee abnormalities at baseline and 48-months were graded on right knee 3T MRIs using a modified whole organ MRI score (WORMS). Statistical analysis employed Student's t-tests and multivariable regression models adjusted for age, body mass index and gender. RESULTS: Extension strength was significantly and positively correlated with baseline thigh muscle CSA (r = 0.65, P < 0.001). Greater baseline total thigh muscle CSA was significantly associated with increase of cartilage WORMS scores over 48 months in patellar (P = 0.027) and trochlear (P = 0.038) compartments, but not in other knee compartments. Among specific muscle groups, CSA of extensors (P = 0.021) and vastus medialis (VM) (P = 0.047) were associated with patellar cartilage increase in WORMS. Baseline E/F ratio had a significant positive association with patellar WORMS cartilage score increase over 48 months, P = 0.0015. There were no other significant associations between muscle CSA/ratios and increase in WORMS scores. CONCLUSION: Maintenance of proper extensor to flexor muscle balance about the knee through decreased E/F ratios may slow patellofemoral cartilage deterioration, while higher extensor and VM CSA may increase patellofemoral cartilage loss.

Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate compositional cartilage changes measured with 3T MRI-based T2 values over 48 months in overweight and obese individuals with different degrees of weight loss (WL) and to study whether WL slows knee cartilage degeneration and symptom worsening. DESIGN: We studied participants from the Osteoarthritis Initiative with risk factors or radiographic evidence of mild to moderate knee osteoarthritis with a baseline BMI ≥25 kg/m(2). We selected subjects who over 48 months lost a, moderate (BMI change, 5-10%WL, n = 180) or large amount of weight (≥10%WL, n = 78) and frequency-matched these to individuals with stable weight (<3%, n = 258). Right knee cartilage T2 maps of all compartments and grey-level co-occurrence matrix (GLCM) texture analyses were evaluated and associations with WL and clinical symptoms (WOMAC subscales for pain, stiffness and disability) were assessed using multivariable regression models. RESULTS: The amount of weight change was significantly associated with change in cartilage T2 of the medial tibia (ß 0.9 ms, 95% CI 0.4 to 1.1, P = 0.001). Increase of T2 in the medial tibia was significantly associated with increase in WOMAC pain (ß 0.5 ms, 95% CI 0.2 to 0.6, P = 0.02) and disability (ß 0.03 ms, 95% CI 0.003 to 0.05, P = 0.03). GLCM contrast and variance over all compartments showed significantly less progression in the >10%WL group compared to the stable weight group (both comparisons, P = 0.04). CONCLUSIONS: WL over 48 months is associated with slowed knee cartilage degeneration and improved knee symptoms.

Longitudinal analysis of cartilage T2 relaxation times and joint degeneration in African American and Caucasian American women over an observation period of 6 years - data from the Osteoarthritis Initiative.

OBJECTIVES: To investigate the change in cartilage T2 values and structural degeneration in knee joints over 72 months in women of African American (AA) vs Caucasian American (CA) ethnicity. METHODS: Knee 3T magnetic resonance imaging (MRIs) from baseline, 24, 48 and 72 months visits of 100 AA and 100 CA women from the Osteoarthritis Initiative (OAI) were assessed for cartilage T2 values and whole-organ magnetic resonance imaging (WORMS) score. Subjects were pair-matched by age, body mass index (BMI), Kellgren-Lawrence (KL) score, clinical site and subcohort within the OAI. We compared the rate of change in whole knee cartilage T2 values and WORMS cartilage, bone marrow edema pattern (BMEP) and meniscus scores between the two ethnic groups using mixed random effects models. RESULTS: At 24 and 48 months 60 subjects and at 72 months 45 subjects per group were available for analysis resulting in 38 complete pairs with data of all time points. Compared to CA, cartilage T2 values in AA increased at a significantly faster rate at baseline (AA: 0.45 ms/y, CA: 0.35 ms/y, P = 0.029) and averaged over 6 years (AA: 0.36 ms/y, CA: 0.27 ms/y, P = 0.039) with changes in both groups reaching a plateau by 48 months. Cartilage, meniscus and BMEP scores tended to increase in both groups during follow up, but rates of change did not differ by ethnicity. CONCLUSION: Cartilage T2 values increased faster over 72 months in AA than CA, however changes in WORMS cartilage, meniscus and BMEP scores did not differ. T2 values may be able to distinguish ethnicity-related differences of cartilage degeneration at an early stage before differences in structural joint degeneration appear.

Do persons with asymmetric hip pain or radiographic hip OA have worse pain and structure outcomes in the knee opposite the more affected hip? Data from the Osteoarthritis Initiative.

PURPOSE: To determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips. METHODS: We studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations. RESULTS: Knees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17). CONCLUSION: These findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

Cortical bone laminar analysis reveals increased midcortical and periosteal porosity in type 2 diabetic postmenopausal women with history of fragility fractures compared to fracture-free diabetics.

UNLABELLED: We investigated the characteristics and spatial distribution of cortical bone pores in postmenopausal women with type 2 diabetes (T2D). High porosity in the midcortical and periosteal layers in T2D subjects with fragility fractures suggests that these cortical zones might be particularly susceptible to T2D-induced toxicity and may reflect cortical microangiopathy. INTRODUCTION: Elevated cortical porosity is regarded as one of the main contributors to the high skeletal fragility in T2D. However, to date, it remains unclear if diabetic cortical porosity results from vascular cortical changes or from an expansion in bone marrow space. Here, we used a novel cortical laminar analysis technique to investigate the characteristics and spatial radial distribution of cortical pores in a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and to compare their results to non-diabetic controls with (Fx) and without fragility fractures (Co). METHODS: Eighty postmenopausal women (n = 20/group) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia and radius. Cortical bone was divided into three layers of equal width including an endosteal, midcortical, and periosteal layer. Within each layer, total pore area (TPA), total pore number (TPN), and average pore area (APA) were calculated. Statistical analysis employed Mann-Whitney tests and ANOVA with post hoc tests. RESULTS: Compared to the DM group, DMFx subjects exhibited +90 to +365 % elevated global porosity (p = 0.001). Cortical laminar analysis revealed that this increased porosity was for both skeletal sites confined to the midcortical layer, followed by the periosteal layer (midcortical +1327 % TPA, p ≤ 0.001, periosteal +634 % TPA, p = 0.002), and was associated in both layers and skeletal sites with high TPN (+430 % TPN, p < 0.001) and high APA (+71.5 % APA, p < 0.001). CONCLUSION: High porosity in the midcortical and periosteal layers in the high-risk T2D group suggests that these cortical zones might be particularly susceptible to T2D-induced toxicity and may reflect cortical microangiopathy.

Association between cartilage degeneration and subchondral bone remodeling in patients with knee osteoarthritis comparing MRI and (99m)Tc-DPD-SPECT/CT.

OBJECTIVE: The purpose of this retrospective cross-sectional study was to investigate the association between cartilage lesions assessed with 3T-MRI and remodeling of the subchondral bone detected by (99m)Tc-DPD-SPECT/CT. DESIGN: (99m)Tc-DPD-SPECT/CT and MRI of 27 knees of 25 patients with chronic knee pain and risk factors for osteoarthritis (OA) were evaluated by one nuclear physician and one radiologist. Six regions of the knee (in total 162 regions in 27 knees) were assessed according to structural joint lesions graded with a modified Whole Organ MR imaging score (WORMS) and according to subchondral (99m)Tc-DPD-SPECT uptake. Relationships between regional WORMS scores and uptake were quantified using general estimating equations. In a secondary analysis the uptake sum with the WORMS sum per joint was compared using Spearman correlations. RESULTS: Elevated subchondral uptake was significantly associated with the grade of cartilage lesions (P < 0.0001). Mean uptake was significantly higher subjacent to full thickness cartilage lesions compared to partial thickness lesions (P < 0.0001). A similar association was observed between bone marrow edema pattern (BMEP) and cartilage lesions. The sum of uptakes per joint was positively correlated to the WORMS sum (rs = 0.42) and to the sum of cartilage lesions per joint (rs = 0.50). CONCLUSION: Both functional and structural changes of the subchondral bone in terms of scintigraphic osseous activity and the presence and degree of BMEP were significantly associated with cartilage lesions in patients with OA of the knee. This association was pronounced with full thickness lesions, indicating a possible protective effect of the cartilage layer for the subjacent bone.

Racial differences in biochemical knee cartilage composition between African-American and Caucasian-American women with 3 T MR-based T2 relaxation time measurements--data from the Osteoarthritis Initiative.

OBJECTIVE: To determine whether knee cartilage composition differs between African-American and Caucasian-American women at risk for Osteoarthritis (OA) using in vivo 3 T MRI T2 relaxation time measurements. METHODS: Right knee MRI studies of 200 subjects (100 African-American women, and 100 closely matched Caucasian-American women) were selected from the Osteoarthritis Initiative (OAI). Knee cartilage was segmented in the patellar (PAT), medial and lateral femoral (MF/LF), and medial and lateral tibial compartments (MT/LT)). Mean T2 relaxation time values per compartment and per whole joint cartilage were generated and analyzed spatially via laminar and grey-level co-occurrence matrix (GLCM) texture methods. Presence and severity of cartilage lesions per compartment were graded using a modified WORMS grading. Statistical analysis employed paired t- and McNemar testing. RESULTS: While African-American women and Caucasian-Americans had similar WORMS cartilage lesion scores (P = 0.970), African-Americans showed significantly lower mean T2 values (∼1 ms difference; ∼0.5SD) than Caucasian-Americans in the whole knee cartilage (P < 0.001), and in the subcompartments (LF: P = 0.001, MF: P < 0.001, LT: P = 0.019, MT: P = 0.001) and particularly in the superficial cartilage layer (whole cartilage: P < 0.001, LF: P < 0.001, MF: P < 0.001, LT: P = 0.003, MT: P < 0.001). T2 texture parameters were also significantly lower in the whole joint cartilage of African-Americans than in Caucasian-Americans (variance: P = 0.001; contrast: P = 0.018). In analyses limited to matched pairs with no cartilage lesions in a given compartment, T2 values remained significantly lower in African-Americans. CONCLUSION: Using T2 relaxation time as a biomarker for the cartilage collagen network, our findings suggest racial differences in the biochemical knee cartilage composition between African-American and Caucasian-American women.

A reference database of cartilage 3 T MRI T2 values in knees without diagnostic evidence of cartilage degeneration: data from the osteoarthritis initiative.

OBJECTIVE: 1) To establish a gender- and BMI-specific reference database of cartilage T2 values, and 2) to assess the associations between cartilage T2 values and gender, age, and BMI in knees without radiographic osteoarthritis or MRI-based (WORMS 0/1) evidence of cartilage degeneration. DESIGN: 481 subjects aged 45-65 years with Kellgren-Lawrence Scores 0/1 in the study knee were selected. Baseline morphologic cartilage 3T MRI readings (WORMS scoring) and T2 measurements (resolution = 0.313 mm × 0.446 mm) were performed in the medial and lateral femurs, medial and lateral tibias, and patella compartments. To create a reference database, a logarithmic transformation was applied to the data to obtain the 5th-95th percentile values for T2. RESULTS: Significant differences in mean cartilage T2 values were observed between joint compartments. Although females had slightly higher T2 values than males in a majority of compartments, the differences were only significant in the medial femur (P < 0.0001). A weak positive association was seen between age and T2 in all compartments, most pronounced in the patella (3.27% increase in median T2/10 years, P = 0.009). Significant associations between BMI and T2 were observed, most pronounced in the lateral tibia (5.33% increase in median T2/5 kg/m(2) increase in BMI, P < 0.0001), and medial tibia (4.81% increase in median T2 /5 kg/m(2) increase in BMI, P < 0.0001). CONCLUSIONS: This study established the first reference database of T2 values in a large sample of morphologically normal cartilage plates in knees without radiographic knee osteoarthritis (OA). While cartilage T2 values were weakly associated with age and gender, they had the highest correlations with BMI.

Association of cartilage degeneration with four year weight gain--3T MRI data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the effect of weight gain on progression of early knee morphologic abnormalities using magnetic resonance imaging (MRI) in a longitudinal study over 48 months. DESIGN: We studied the right knee of 100 subjects from the Osteoarthritis Initiative (OAI), selecting subjects aged ≥ 45 with osteoarthritis (OA) risk factors who demonstrated weight gain (minimum 5% increase in body mass index, BMI, n = 50) or no change in weight (BMI change < 2%, n = 50), frequency matched for age, gender, and baseline BMI. Baseline and 48 month knee MRI studies were scored for lesions using a modified whole organ MRI score (WORMS). Logistic regression models were used to compare the differences between the two groups. RESULTS: The odds of worsening maximum cartilage (11.3, 95%, CI 3.5-51.4) and meniscal WORMS (4.5, 95% CI 1.4-17.3) were significantly greater in the weight gain group compared to the no change group, in addition to the odds of worsening cartilage defects at the patella and average meniscal WORMS (P < 0.05). Odds of worsening average bone marrow edema pattern (BMEP) were significantly greater for the weight gain group compared to the no change cohort (P < 0.05). CONCLUSION: Our study demonstrated that weight gain is strongly associated with increased progression of cartilage degeneration in middle-aged individuals with risk factors for OA.

Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures.

UNLABELLED: While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future. INTRODUCTION: Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture risk profiles. We examined a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and compared their results to nondiabetic controls with (Fx) and without fragility fractures (Co). METHODS: Eighty postmenopausal women (n = 20 per group) underwent quantitative computed tomography (QCT) to compute vBMD and bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D, parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels were measured. Statistical analyses employed linear regression models. RESULTS: DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects across all femoral sites (-19 % ≤ ΔvBMD ≤ -33 %, 0.008 ≤ p ≤0.021). Additionally, DMFx subjects showed significantly thinner cortices (-6 %, p = 0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM women and higher serum sclerostin levels when compared to DM (+31.4 %, p = 0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects. CONCLUSION: Our data suggest that volumetric bone parameters by QCT and serum sclerostin levels can identify T2D individuals at high risk of fracture and might therefore show promise as clinical tools for fracture risk assessment in T2D. However, future research is needed to establish diabetes-specific QCT- and sclerostin-reference databases.