Analysis of Hand Joint Space Morphology in Women and Men with Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) causes unbalanced iron deposition in many organs including the joints leading to severe cartilage loss and bone damage in the metacarpophalangeal joints (MCPJ). High-resolution peripheral quantitative computed tomography (HR-pQCT) and its joint space width (JSW) quantification algorithm quantifies in vivo 3D joint morphology. We therefore aimed to (i) determine feasibility and performance of the JSW algorithm in HH, (ii) quantify joint space morphology, and (iii) investigate the relationship between morphological and clinical parameters in HH. Here, we performed an exploratory study on 24 HH patients and sex- and age-matched controls using HR-pQCT imaging of MCPJ. Mineralized bone structure was automatically segmented from the grayscale image data and periosteal surface bone masks and joint space masks were generated. Mean, minimal, and maximal joint space width (JSW; JSW.MIN; JSW.MAX), JSW heterogeneity (JSW.SD), JSW asymmetry (JSW.AS), and joint space volume (JSV) were computed. Demographics and, for HH patients, disease-specific parameters were recorded. Segmentation of JS was very good with 79.7% of MCPJs successfully segmented at first attempt and 20.3% requiring semi-manual correction. HH men showed larger JSV at all MCPs (+ 25.4% < JSV < + 41.8%, p < 0.05), larger JSW.MAX at MCP 3-4 (+ 14%, 0.006 < p < 0.062), and wider JSW (+ 13%, p = 0.043) at MCP 4 relative to HH women. Compared to controls, both HH men and HH women showed larger JSW.AS and smaller JSW.MIN at all MCP levels, reaching significance for HH men at MCP 2 and 3 (JSW.AS: + 323% < JSW.AS < + 359%, 0.020 < p < 0.043; JSW.MIN: - 216% < JSW.MIN < - 225%, p < 0.043), and for women at MCP 3 (JSW.AS: + 180%, p = 0.025; JSW.MIN: - 41.8%, p = 0.022). Time since HH diagnosis was correlated positively with MCP 4 JSW.AS and JSW.SD (0.463 < ρ < 0.499, p < 0.040), and the number of phlebotomies since diagnosis was correlated with JSW.SD at all MCPs (0.432 < ρ < 0.535, p < 0.050). HR-pQCT-based JSW quantification in MCPJ of HH patients is feasible, performs well even in narrow JS, and allows to define the microstructural joint burden of HH.

Circulating serum microRNAs including senescent miR-31-5p are associated with incident fragility fractures in older postmenopausal women with type 2 diabetes mellitus.

Fragility fractures are an important hallmark of aging and an increasingly recognized complication of Type 2 diabetes (T2D). T2D individuals have been found to exhibit an increased fracture risk despite elevated bone mineral density (BMD) by dual x-ray absorptiometry (DXA). However, BMD and FRAX-scores tend to underestimate fracture risk in T2D. New, reliable biomarkers are therefore needed. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity. Serum miRNA-classifiers were recently found to discriminate T2D women with and without prevalent fragility fractures with high specificity and sensitivity (AUC > 0.90). However, the association of circulating miRNAs with incident fractures in T2D has not been examined yet. In 168 T2D postmenopausal women in the AGES-Reykjavik cohort, miRNAs were extracted from baseline serum and a panel of 10 circulating miRNAs known to be involved in diabetic bone disease and aging was quantified by qPCR and Ct-values extracted. Unadjusted and adjusted Cox proportional hazard models assessed the associations between serum miRNAs and incident fragility fracture. Additionally, Receiver operating curve (ROC) analyses were performed. Of the included 168 T2D postmenopausal women who were on average 77.2 ±â€¯5.6 years old, 70 experienced at least one incident fragility fracture during the mean follow-up of 5.8 ±â€¯2.7 years. We found that 3 serum miRNAs were significantly associated with incident diabetic fragility fracture: while low expression of miR-19b-1-5p was associated with significantly lower risk of incident fragility fracture (HR 0.84 (95% CI: 0.71-0.99, p = 0.0323)), low expression of miR-203a and miR-31-5p was each significantly associated with a higher risk of incident fragility fracture per unit increase in Ct-value (miR-203a: HR 1.29 (95% CI: 1.12-1.49), p = 0.0004, miR-31-5p HR 1.27 (95% CI: 1.06-1.52), p = 0.009). Hazard ratios of the latter two miRNAs remained significant after adjustments for age, body mass index (BMI), areal bone mineral density (aBMD), clinical FRAX or FRAXaBMD. Women with miR-203a and miR-31-5p serum levels in the lowest expression quartiles exhibited a 2.4-3.4-fold larger fracture risk than women with miR-31-5p and miR-203a serum expressions in the highest expression quartile (0.002 ≤ p ≤ 0.039). Women with both miR-203a and miR-31-5p serum levels below the median had a significantly increased fracture risk (Unadjusted HR 3.26 (95% CI: 1.57-6.78, p = 0.001) compared to those with both expression levels above the median, stable to adjustments. We next built a diabetic fragility signature consisting of the 3 miRNAs that showed the largest associations with incident fracture (miR-203a, miR-31-5p, miR-19b-1-5p). This 3-miRNA signature showed with an AUC of 0.722 comparable diagnostic accuracy in identifying incident fractures to any of the clinical parameters such as aBMD, Clinical FRAX or FRAXaBMD alone. When the 3 miRNAs were combined with aBMD, this combined 4-feature signature performed with an AUC of 0.756 (95% CI: 0.680, 0.823) significantly better than aBMD alone (AUC 0.666, 95% CI: 0.585, 0.741) (p = 0.009). Our data indicate that specific serum microRNAs including senescent miR-31-5p are associated with incident fragility fracture in older diabetic women and can significantly improve fracture risk prediction in diabetics when combined with aBMD measurements of the femoral neck.

Inflammatory arthritis in systemic sclerosis is associated with elevated C-reactive protein and requires musculoskeletal ultrasound for reliable detection.

Objectives: About 25% of patients with systemic sclerosis (SSc) have elevated C-reactive protein (CRP) levels. Specific causes of CRP elevation are unknown so far. We aimed to investigate whether inflammatory arthritis is associated with CRP elevation. Furthermore, we evaluated the sensitivity and specificity of clinical examination compared to musculoskeletal ultrasound (MSUS) for detection of arthritis. Methods: Sixty-five patients with SSc (51 females) were enrolled and allocated into a CRP-positive (CRP+, n = 20; CRP elevated for at least two years prior to enrollment) and a CRP-negative (CRP-; n = 45) cohort. All patients were examined clinically (modified Rodnan Skin Score, mRSS; swollen/tender joint count 66/68), received a comprehensive MSUS of their hands and feet, as well as laboratory testing (antibody status; CRP). Statistical analyses were performed using non-parametrical tests without adjustments. Results: Patient with a disease duration <3 years had higher CRP levels (p = 0.042). Anti-centromere antibodies dominated in CRP- patients (p = 0.013), and anti-Scl70 antibodies in CRP + patients (p = 0.041). Joint effusion and B-mode synovitis prevailed in male (p < 0.00001; p < 0.0001) and CRP + (p = 0.001; p < 0.00001) patients. Power Doppler (PD)-synovitis predominated in patients with diffuse SSc (p = 0.0052). Joint effusion and B-/PD-synovitis were mostly confined to wrists, MTPs and talo-navicular joints. Compared to MSUS, sensitivity of clinical examination was as low as 14.6%; specificity was 87.7%. Sensitivity was reduced by the presence of soft tissue edema or a mRSS > 10. Conclusion: Arthritis is more frequent in CRP + compared to CRP- SSc patients. Compared to MSUS sensitivity of clinical examination is low for the detection of arthritis; this is likely due to skin fibrosis and soft tissue edema. Therefore, regular monitoring via MSUS should be considered as routine assessment in SSc patients.

Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures-A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography.

Introduction: Diabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT). Methods: Thirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups. Results: At baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020). Conclusion: Our data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength-depending on the amount of early cortical pre-damage.

Central osteophytes develop in cartilage with abnormal structure and composition: data from the Osteoarthritis Initiative cohort.

OBJECTIVE: To investigate the natural history of central osteophytes (COs) by analyzing the structure and matrix composition of CO-associated cartilage using 3-T MRI at and 1-3 years before the onset of COs. MATERIALS AND METHODS: Baseline, 4- and 6-year knee MRIs of 400 participants in the Osteoarthritis Initiative were screened for the appearance of new COs. Twenty-eight subjects developed 31 COs. Using MRIs at CO onset and 1-3 years before CO onset, cartilage T2 values were calculated for the local cartilage preceding COs and the surrounding cartilage. Cartilage lesions local to the site of COs and bone marrow edema like lesions (BMELs) subjacent to COs were graded using whole organ MRI scores (WORMS). Wilcoxon tests were used to compare T2 values from the local and the surrounding cartilage at each time point and to compare T2 and WORMS between time points. Knee symptoms were recorded during this period. RESULTS: All subjects showed local cartilage lesions before the development of COs. Mean cartilage WORMS increased from 1.56 ± 0.66 a period of 3 years before to 2.39 ± 0.75 with onset of COs (p = 0.008). Local T2 values in the area of the later-appearing COs were significantly higher compared with T2 values of the surrounding cartilage 3 (p = 0.044) and 2 years earlier (p = 0.031) and with the onset of COs (p = 0.025). No significant increase in symptoms was found with the onset of COs. CONCLUSION: This study provides evidence that focal cartilage structural and compositional degeneration precedes COs. No significant aggravation of knee symptoms was reported during the evolution of COs.

Structural Changes over a Short Period Are Associated with Functional Assessments in Rheumatoid Arthritis.

OBJECTIVE: To investigate the correlation between changes in radiological quantitative assessment with changes in clinical and functional assessment from baseline to 3 months in patients with rheumatoid arthritis (RA). METHODS: Twenty-eight patients with RA [methotrexate (MTX) and anti-tumor necrosis factor-α (TNF-α) group with high disease activity (n = 18); and MTX group with low disease activity (n = 10)] underwent assessments at baseline and 3 months: clinical [28-joint count Disease Activity Score (DAS28)], functional [Health Assessment Questionnaire (HAQ) and Michigan Hand Outcome Questionnaire (MHQ)], and imaging-based [3 Tesla magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT)]. MR images were evaluated semiquantitatively [RA MRI scoring (RAMRIS)] and quantitatively for the volume of synovitis and bone marrow edema (BME) lesions. Erosion volumes were measured using HR-pQCT. RESULTS: After 3 months, the anti-TNF-α group demonstrated an improvement in disease activity through DAS28, HAQ, and MHQ. MRI showed significant decreases in synovitis and BME volume for the anti-TNF-α group, and significant increases in the MTX group. HR-pQCT showed significant decreases in bone erosion volume for the anti-TNF-α group, and significant increases in the MTX group. No significance was observed using RAMRIS. Changes in synovitis, BME, and erosion volumes, but not RAMRIS, were significantly correlated with changes in DAS28, HAQ, and MHQ. CONCLUSION: Quantitative measures were more sensitive than semiquantitative grading when evaluating structural and inflammatory changes with treatment, and were associated with patient clinical and functional outcomes. Multimodality imaging with 3T MRI and HR-pQCT may provide promising biomarkers that help determine disease progression and therapy response.

Baseline knee joint effusion and medial femoral bone marrow edema, in addition to MRI-based T2 relaxation time and texture measurements of knee cartilage, can help predict incident total knee arthroplasty 4-7 years later: data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate if baseline pathological knee conditions as assessed via single features of the MR-based Whole-Organ Magnetic Resonance Imaging Scoring (WORMS), standard T2, and T2 gray-level co-occurrence matrix (GLCM) texture parameters of knee cartilage can serve as potential long-term radiological predictors of incident total knee arthroplasty (TKA) 4-7 years later. MATERIALS AND METHODS: Baseline 3-T knee MRIs of 309 subjects from the Osteoarthritis Initiative (n = 81 TKA cases, with right-knee TKA 4-7 years after enrolment, and n = 228 TKA-free matched controls) were evaluated for the presence and severity of pathological knee conditions via modified WORMS. Knee cartilage was segmented and standard T2 cartilage and T2 GLCM texture measures (contrast, variance) were computed. Statistical analysis employed conditional logistic regression. RESULTS: We found that a one-point increase on the joint effusion scale, the bone marrow edema scale or on the cartilage lesion scale at baseline predicted incident TKA (ORs: 2.45, 1.65, and 1.37 respectively (p ≤ 0.003)). For T2 cartilage measurements, we observed that in the lateral femur, a 1-SD increase in T2 relaxation time yielded a 28% increase in the odds of TKA (1.28 [1.09-1.643], p = 0.046). When looking at cartilage texture, we similarly noted that a 1-SD increase in the cartilage texture parameter "contrast" was associated with a 33-40% increased risk of incident TKA in the lateral femur and tibia (0.003 ≤ p ≤ 0.021), as was a 1-SD increase in the texture parameter "variance" in the lateral femur (p = 0.002). CONCLUSION: Radiological evaluation of standard knee MR images via single WORMS features and T2 standard and texture analysis at baseline can help predict the patient's individual risk for an incident TKA 4-7 years later.

Diabetics show accelerated progression of knee cartilage and meniscal lesions: data from the osteoarthritis initiative.

OBJECTIVE: To investigate whether subjects with diabetes show accelerated knee joint structural degeneration over 4 years compared to diabetes-free controls. MATERIALS AND METHODS: Two hundred forty-four participants with diabetes were selected from the Osteoarthritis Initiative cohort and matched with 244 diabetes-free controls. 3.0-T MRI scans of the right knee were obtained at baseline and 4-year follow-up. Evaluation of structural knee abnormalities was performed using the Whole-Organ Resonance Imaging Scoring system (WORMS). Linear regression analysis was conducted to compare structural temporal changes in each compartment, as well as the mean across all compartments by diabetes status. RESULTS: Study groups were similar in age (63.0 vs. 63.3 years, p = 0.73), body mass index (31.5 vs. 31.0 kg/m2, p = 0.21), sex (female 52.0 vs. 52.9%, p = 0.85) and radiographic Kellgren/Lawrence score distribution (p = 0.99). Structural degeneration was significantly worse in the knees of diabetics with an increase in the overall WORMS sum score (delta WORMS [95% CI]: 4.87 [4.17, 5.57], vs. 3.23 [2.60, 3.85] p = 0.001). Moreover, diabetics showed a greater increase in cartilage lesions in the global knee (p < 0.001), but also separately in the patella, lateral tibia, and both femoral compartments (lowest p value; p = 0.001). Furthermore, diabetics showed also a greater increase in meniscus lesion score, in both the medial (p = 0.01) and lateral meniscus (p = 0.01). CONCLUSIONS: Diabetics exhibited a significantly greater increase in cartilage and meniscus lesions when compared to diabetes-free controls over 4 years. Overall, our findings suggest that diabetics exhibit a stronger deterioration of knee structure and are therefore potentially at higher risk for developing knee OA.

Tool for osteoarthritis risk prediction (TOARP) over 8 years using baseline clinical data, X-ray, and MRI: Data from the osteoarthritis initiative.

BACKGROUND: Osteoarthritis (OA), a multifactorial disease causing joint degeneration, often leads to severe disability. The rising rates of disability highlight the need for implementing preventative measures at early stages of the disease, which would especially benefit subjects at high risk for OA development. PURPOSE: To develop a risk prediction tool for moderate-severe OA (TOARP) over 8 years based on subject characteristics, knee radiographs, and MRI data at baseline using data from the Osteoarthritis Initiative (OAI). STUDY TYPE: Retrospective. SUBJECTS: 641 subjects with no/mild radiographic OA (Kellgren-Lawrence [KL] 0-2) and no clinically significant symptoms (Western Ontario and McMaster Universities Arthritis Index [WOMAC] 0-1) were selected from the OAI. FIELD STRENGTH/SEQUENCE: MR images were obtained using 3.0T. ASSESSMENT: Compartment-specific cartilage and meniscus morphology and cartilage T2 were assessed. Baseline subject demographics, risk factors, KL score, cartilage WORMS score, presence of meniscus tear, and cartilage T2 were used to predict the development of moderate/severe OA (KL = 3-4 or WOMAC pain ≥5 or total knee replacement [TKR]) over 8 years. STATISTICAL TESTS: Best subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA. RESULTS: Model 1 included KL score, previous knee injury in the last 12 months, age, gender, and BMI. Model 2 included all variables in Model 1 plus presence of cartilage defects in the lateral femur and patella, and presence of a meniscal tear. Model 3 included all variables in Models 1 and 2, plus cartilage T2 in the medial tibia and medial femur. Compared to Model 1 (cross-validated AUC = 0.67), Model 3 performed significantly better (AUC = 0.72, P = 0.04), while Model 2 showed a statistical trend (AUC = 0.71, P = 0.08). DATA CONCLUSION: We established a risk calculator for the development of moderate/severe knee OA over 8 years that includes radiographic and MRI data. The inclusion of MRI-based morphological abnormalities and cartilage T2 significantly improved model performance. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526.

Association of diabetes mellitus and biochemical knee cartilage composition assessed by T2 relaxation time measurements: Data from the osteoarthritis initiative.

PURPOSE: To investigate the association of the presence and severity of diabetes mellitus (DM) with articular cartilage composition, using magnetic resonance imaging (MRI)-based T2 relaxation time measurements, and structural knee abnormalities. MATERIALS AND METHODS: In the Osteoarthritis Initiative 208, participants with DM (age 63.0 ± 8.9 years; 111 females) and risk factors for osteoarthritis (OA) or mild radiographic tibiofemoral OA (Kellgren-Lawrence [KL] grade ≤2) were identified and group-matched with 208 controls without DM (age 63.3 ± 9.1 years; 111 females). Subjects with diabetes-related renal or ophthalmological complications or insulin treatment at baseline (n = 50) were defined as severe DM. 3T MR images of the right knee were assessed for articular cartilage T2 , including texture and laminar analyses derived from the patella, medial, and lateral femur and tibia and for structural abnormalities using the modified whole-organ magnetic resonance imaging score (WORMS). Clustered linear regression analyses were used to assess associations of DM with MRI findings. RESULTS: DM subjects had significantly higher cartilage T2 in the patella (mean difference 0.92 msec [95% confidence interval (CI) 0.79, 1.06]; P = 0.001) and medial femur (mean difference 0.36 msec [95% CI 0.27, 0.81]; P = 0.006) compared to controls. Averaged over all compartments, DM subjects showed significantly higher texture parameters (variance, P = 0.001; contrast, P = 0.002; entropy, P < 0.001). Subjects with severe DM additionally showed higher T2 in the medial tibial deep and superficial layers (P = 0.011 and P = 0.041) compared to controls. No significant differences in cartilage, meniscus, and overall WORMS were found between the groups (P > 0.05). CONCLUSION: In comparison to nondiabetic controls, cartilage in DM subjects showed higher and more heterogeneous cartilage T2 values, indicating increased articular cartilage degeneration. This affected even more compartments in subjects with severe DM. LEVEL OF EVIDENCE: 2 Technical Efficacy: 5 J. Magn. Reson. Imaging 2018;47:380-390.

Conservatively treated knee injury is associated with knee cartilage matrix degeneration measured with MRI-based T2 relaxation times: data from the osteoarthritis initiative.

OBJECTIVE: To investigate the association of cartilage degeneration with previous knee injuries not undergoing surgery, determined by morphologic and quantitative 3-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: We performed a nested cross-sectional study of right knee MRIs from participants in the Osteoarthritis Initiative (OAI) aged 45-79 with baseline Kellgren-Lawrence score of 0-2. Cases were 142 right knees of patients with self-reported history of injury limiting the ability to walk for at least 2 days. Controls were 426 right knees without history of injury, frequency-matched to cases on age, BMI, gender, KL scores and race (1:3 ratio). Cases and controls were compared using covariate-adjusted linear regression analysis, with the outcomes of region-specific T2 mean, laminar analysis and heterogeneity measured by texture analysis to investigate early cartilage matrix abnormalities and the Whole-Organ Magnetic Resonance Imaging Score (WORMS) to investigate morphologic knee lesions. RESULTS: Compared to control subjects, we found significantly higher mean T2 values in the injury [lateral tibia (28.10 ms vs. 29.11 ms, p = 0.001), medial tibia (29.70 ms vs. 30.40 ms, p = 0.014) and global knee cartilage (32.73 ms vs. 33.29 ms, p = 0.005)]. Injury subjects also had more heterogeneous cartilage as measured by GLCM texture contrast, variance and entropy (p < 0.05 in 14 out of 18 texture parameters). WORMS gradings were not significantly different between the two groups (p > 0.05). CONCLUSION: A history of knee injury not treated surgically is associated with higher and more heterogeneous T2 values, but not with morphologic knee abnormalities. Our findings suggest that significant, conservatively treated knee injuries are associated with permanent cartilage matrix abnormalities.

Assessment of 3-month changes in bone microstructure under anti-TNFα therapy in patients with rheumatoid arthritis using high-resolution peripheral quantitative computed tomography (HR-pQCT).

BACKGROUND: Although one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Patients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively. RESULTS: Overall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R 2 = 0.311, p = 0.013; R 2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R 2 = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R 2 = 0.558, p < 0.001; R 2 = 0.745, p < 0.001, respectively) in all patients. CONCLUSIONS: Using HR-pQCT, our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period. Patients with low disease activity scores (<3.2) can have continuous HR-pQCT-detectable progression of erosive disease with MTX treatment only. HR-pQCT can be a sensitive, powerful tool to quantify bone changes and monitor RA treatment short term (such as 3 months).

Medial femur T2 Z-scores predict the probability of knee structural worsening over 4-8 years: Data from the osteoarthritis initiative.

OBJECTIVE: The purpose of this study was to determine the probability of structural worsening of knee cartilage and whole joint degeneration over 4-8 years based on cartilage T2 Z-scores at baseline. DESIGN: Right knees with Kellgren-Lawrence (KL) grades of 0-2 in 587 participants from the Osteoarthritis Initiative were studied. 3T MR images were used to perform baseline cartilage T2 quantification and assess 4-year changes in cartilage morphology (WORMS scoring) in 5 regions. Changes in joint space narrowing (JSN) and KL were assessed over 8 years. T2 Z-scores were based on a reference database of knees without morphologic cartilage degeneration at baseline. Odds ratios for, and predicted probabilities of any worsening in WORMS cartilage, JSN and KL grade were obtained from logistic regression models. RESULTS: A one-unit increase in the baseline medial femur T2 Z-score was associated with cartilage worsening in the same region (OR = 1.59; P < 0.0001) and in any region (OR = 1.37; P < 0.0001), and with worsening JSN (OR = 1.82; P < 0.0001) and KL grades (OR = 1.69; P < 0.0001). Predicted probabilities of worsening in knees with a medial femur T2 Z-score from 2-4 were 38% for medial femur cartilage WORMS, 70% for any cartilage region, 28% for increasing JSN and 31% for increasing KL grade. CONCLUSION: Knees with elevated cartilage T2 (especially in the medial femur and those that are 2 to 4 SDs above the mean reference values) are significantly more likely to have structural worsening over 4 to 8 years. Knowing cartilage T2 Z-scores may aid in targeting prevention efforts at early stages of osteoarthritis. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1128-1136.

Evaluation of Chondrocalcinosis and Associated Knee Joint Degeneration Using MR Imaging: Data from the Osteoarthritis Initiative.

OBJECTIVES: To evaluate the ability of different MRI sequences to detect chondrocalcinosis within knee cartilage and menisci, and to analyze the association with joint degeneration. METHODS: Subjects with radiographic knee chondrocalcinosis (n = 90, age 67.7 ± 7.3 years, 50 women) were selected from the Osteoarthritis Initiative and matched to controls without radiographic chondrocalcinosis (n = 90). Visualization of calcium-containing crystals (CaC) was compared between 3D T1-weighted gradient-echo (T1GE), 3D dual echo steady-state (DESS), 2D intermediate-weighted (IW), and proton density (PD)-weighted fast spin-echo (FSE) sequences obtained with 3T MRI and correlated with a semiquantitative CaC score obtained from radiographs. Structural abnormalities were assessed using Whole-Organ MRI Score (WORMS) and logistic regression models were used to compare cartilage compartments with and without CaC. RESULTS: Correlations between CaC counts of MRI sequences and degree of radiographic calcifications were highest for GE (rT1GE = 0.73, P < 0.001; rDESS = 0.68, P < 0.001) compared to other sequences (P > 0.05). Meniscus WORMS was significantly higher in subjects with chondrocalcinosis compared to controls (P = 0.005). Cartilage defects were significantly more frequent in compartments with CaC than without (patella: P = 0.006; lateral tibia: P < 0.001; lateral femur condyle: P = 0.017). CONCLUSIONS: Gradient-echo sequences were most useful for the detection of chondrocalcinosis and presence of CaC was associated with higher prevalence of cartilage and meniscal damage. KEY POINTS: • Magnetic resonance imaging is useful for assessing burden of calcium-containing crystals (CaC). • Gradient-echo sequences are superior to fast spin echo sequences for CaC imaging. • Presence of CaC is associated with meniscus and cartilage degradation.

Evaluating radiocarpal cartilage matrix changes 3-months after anti-TNF treatment for rheumatoid arthritis using MR T1ρ imaging.

PURPOSE: To evaluate the feasibility of MR T1ρ in assessing radiocarpal cartilage matrix changes following rheumatoid arthritis (RA) treatment. MATERIALS AND METHODS: Five healthy controls and nine RA patients were studied: three RA patients with low disease activity that were treated with methotrexate (MTX) alone and six with active disease despite MTX treatment who were additionally treated with certolizumab pegol, an anti-tumor necrosis factor biologic. Wrist 3 Tesla MRI were acquired at baseline and 3-month follow-up. T1ρ were quantified for lunar, radius, and scaphoid cartilage. Reproducibility was evaluated using coefficients of variation (CV). Longitudinal changes were evaluated with t-test and relationships between T1ρ with clinical, MRI, and patient-reported outcomes were evaluated with Spearman's rho. RESULTS: Scan/re-scan CVs of T1ρ values were all <5%, and intra- and inter-reader CVs were all < 2.0%. Baseline scaphoid T1ρ values were significantly higher in RA patients compared with healthy controls (P = 0.032). Changes in T1ρ (baseline, 3-month) were correlated with EULAR treatment response criteria: -2.26 ± 0.75 ms, 1.08 ± 0.52 ms, and 2.18 ± 0.45 ms for good, moderate, and nonresponders, respectively. Significant correlations were found between changes in global T1ρ values and changes in DAS28-CRP (rs = 0.683; P = 0.042), MHQ (rs = -0.783; P = 0.013), and HAQ (rs = 0.833; P = 0.010). CONCLUSION: Despite the limited sample size and follow-up time points, there were significant correlations between changes in radiocarpal T1ρ and changes in disease activity as assessed by clinical and patient-reported outcomes. Our findings encourage further research into MR T1ρ assessment of RA disease activity and treatment response. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1514-1522.

Bone Quality-Beyond Bone Mineral Density.

Both bone mass and quality are responsible for bone strength. Whereas bone mass is measured with bone mineral density, quantification of bone quality is more complex and involves bone architecture, texture, and mechanical parameters. Over the last decade, significant progress has been made in developing technologies to measure bone quality. These include novel low-cost modalities such as trabecular bone score measured on dual-energy X-ray absorptiometry images and quantitative ultrasound as well as more advanced imaging modalities such as multidetector computed tomography, magnetic resonance imaging, and high-resolution peripheral quantitative computed tomography. We describe the reasons to measure bone quality and present the different modalities currently used to quantify it. This article also summarizes the strengths and weaknesses as well as the clinical feasibility of these technologies.

Diabetes and Bone.

Skeletal fragility has been recognized as an important feature of diabetes mellitus type 1 (T1D) and type 2 (T2D). While patients with DM1 typically display low bone mineral density (BMD) and concomitant increases in fracture risk, T2D bone disease is more complex and less understood. Although BMD is often normal or even slightly elevated, the risk of fragility fractures is disproportionally high. Alterations in bone quality (i.e., bone microstructure and matrix properties) have been reported by independent groups of researchers. Cortical porosity and the deposition of advanced glycation end-products appear to play key roles. Paired with low bone turnover, another distinct feature of T2D bone disease, secondary complications (including nephropathy, neuropathy, and angiopathy) are adding up to form a complex entity distinct from postmenopausal and age-related osteoporosis. This article offers an overview of current concepts in pathophysiology, clinical features, and imaging features of diabetic bone disease.

Osteoporosis Imaging in the Geriatric Patient.

Given the expected rapid growth of the geriatric world population (=individuals aged >65 years) to 1.3 billion by 2050, age-related diseases such as osteoporosis and its sequelae, osteoporotic fractures, are on the rise. Areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) is the current gold standard to diagnose osteoporosis, to assess osteoporotic fracture risk, and to monitor treatment-induced BMD changes. However, most fragility fractures occur in patients with normal or osteopenic aBMD, indicating that factors beyond BMD impact bone strength. Recent developments in DXA technology such as TBS, VFA, and hip geometry analysis are now available to assess some of these non-BMD parameters from the DXA image. This review will discuss the use of DXA and DXA-assisted technologies and their respective advantages and disadvantages. Special attention is given to if and how each method is indicated in the geriatric population, and the latest ISCD 2015 guidelines have been incorporated.

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro.

Standard DXA measurements, including Fracture Risk Assessment Tool (FRAX) scores, have shown limitations in assessing fracture risk in Type 2 Diabetes (T2D), underscoring the need for novel biomarkers and suggesting that other pathomechanisms may drive diabetic bone fragility. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity and were recently found to be crucial to bone homeostasis and T2D. Here, we studied, if and which circulating miRNAs or combinations of miRNAs can discriminate best fracture status in a well-characterized study of diabetic bone disease and postmenopausal osteoporosis (n = 80 postmenopausal women). We then tested the most discriminative and most frequent miRNAs in vitro. Using miRNA-qPCR-arrays, we showed that 48 miRNAs can differentiate fracture status in T2D women and that several combinations of four miRNAs can discriminate diabetes-related fractures with high specificity and sensitivity (area under the receiver-operating characteristic curve values [AUCs], 0.92 to 0.96; 95% CI, 0.88 to 0.98). For the osteoporotic study arm, 23 miRNAs were fracture-indicative and potential combinations of four miRNAs showed AUCs from 0.97 to 1.00 (95% CI, 0.93 to 1.00). Because a role in bone homeostasis for those miRNAs that were most discriminative and most present among all miRNA combinations had not been described, we performed in vitro functional studies in human adipose tissue-derived mesenchymal stem cells to investigate the effect of miR-550a-5p, miR-188-3p, and miR-382-3p on osteogenesis, adipogenesis, and cell proliferation. We found that miR-382-3p significantly enhanced osteogenic differentiation (p < 0.001), whereas miR-550a-5p inhibited this process (p < 0.001). Both miRNAs, miR-382-3p and miR-550a-5p, impaired adipogenic differentiation, whereas miR-188-3p did not exert an effect on adipogenesis. None of the miRNAs affected significantly cell proliferation. Our data suggest for the first time that miRNAs are linked to fragility fractures in T2D postmenopausal women and should be further investigated for their diagnostic potential and their detailed function in diabetic bone. © 2016 American Society for Bone and Mineral Research.

MRI findings associated with development of incident knee pain over 48 months: data from the osteoarthritis initiative.

PURPOSE: The purpose of this nested case-control study was to identify baseline, incident, and progressive MRI findings visible on standard MRI clinical sequences that were associated with development of incident knee pain in subjects at risk for OA over a period of 48 months. METHODS: We analyzed 60 case knees developing incident pain (WOMAC(pain) = 0 at baseline and WOMAC(pain) ≥ 5 at 48 months) and 60 control knees (WOMAC(pain) = 0 at baseline and WOMAC(pain) = 0 at 48 months) from the Osteoarthritis Initiative. 3 T knee MRIs were analyzed using a modified WORMS score (cartilage, meniscus, bone marrow) at baseline and after 48 months. Baseline and longitudinal findings were grouped into logistic regression models and compared using likelihood-ratio tests. For each model that was significant, a stepwise elimination was used to isolate significant MRI findings. RESULTS: One baseline MRI finding and three findings that changed from baseline to 48 months were associated with the development of pain: at baseline, the severity of a cartilage lesion in the medial tibia was associated with incident pain--(odds ratio (OR) for incident pain = 3.05; P = 0.030). Longitudinally, an incident effusion (OR = 9.78; P = 0.005), a progressive cartilage lesion of the patella (OR = 4.59; P = 0.009), and an incident medial meniscus tear (OR = 4.91; P = 0.028) were associated with the development of pain. CONCLUSIONS: Our results demonstrate that baseline abnormalities of the medial tibia cartilage as well as an incident joint effusion, progressive patella cartilage defects, and an incident medial meniscus tear over 48 months may be associated with incident knee pain. Clinically, this study helps identify MRI findings that are associated with the development of knee pain.