Infrapatellar fat pad abnormalities are associated with a higher inflammatory synovial fluid cytokine profile in young adults following ACL tear.

OBJECTIVE: To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1ρ and T2 relaxation time measurements. DESIGN: 26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1ρ and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data. RESULTS: The degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-γ (ρpartial = 0.64, 95% CI (0.26-0.85)), IL-10 (ρpartial = 0.47, 95% CI (0.04-0.75)), IL-6 (ρpartial = 0.56, 95% CI (0.16-0.81)), IL-8 (ρpartial = 0.49, 95% CI (0.06-0.76)), TNF-α (ρpartial = 0.55, 95% CI (0.14-0.80)) and of the chondrodestructive markers MMP-1 and -3 (MMP-1: ρpartial = 0.57, 95% CI (0.17-0.81); MMP-3: ρpartial = 0.60, 95% CI (0.21-0.83)). IPFP abnormalities were significantly associated with higher T1ρ and T2 values in the trochlear cartilage (T1ρ: ρpartial = 0.55, 95% CI (0.15-0.80); T2: ρpartial = 0.58, 95% CI (0.18-0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 ≤ ρpartial ≤ 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (ρpartial = 0.57, 95% CI (0.17-0.81)). CONCLUSIONS: This exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.

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.

Magnetic resonance imaging lesions are more severe and cartilage T2 relaxation time measurements are higher in isolated lateral compartment radiographic knee osteoarthritis than in isolated medial compartment disease - data from the Osteoarthritis Initiative.

OBJECTIVE: Isolated lateral compartment tibiofemoral radiographic osteoarthritis (IL-ROA) is an understudied form of knee osteoarthritis (OA). The objective of the present study was to characterize Magnetic Resonance Imaging (MRI) abnormalities and MR-T2 relaxation time measurements associated with IL-ROA and with isolated medial compartment ROA (IM-ROA) compared with knees without OA. METHOD: 200 case subjects with IL-ROA (Kellgren/Lawrence (K/L) grade≥2 and joint space narrowing (JSN) > 0 in the lateral compartment but JSN = 0 in the medial compartment) were randomly selected from the Osteoarthritis Initiative baseline visit. 200 cases with IM-ROA and 200 controls were frequency matched to the IL-ROA cases. Cases and controls were analyzed for odds of having a subregion with >10% cartilage area affected, with ≥25% bone marrow lesions (BML), with meniscal tear or maceration, and for association with cartilage T2 values. RESULTS: IL-ROA was more strongly associated with ipsilateral MRI knee pathologies than IM-ROA (IL-ROA: OR = 135.2 for size of cartilage lesion, 95% CI 42.7-427.4; OR = 145.4 for large size BML, 95% CI 41.5-509.5; OR = 176 for meniscal tears, 95% CI 59.8-517.7; IM-ROA: OR = 28.4 for size of cartilage lesion, 95% CI 14.7-54.7; OR = 38.1 for size of BML, 95% CI 12.7-114; OR = 37.0 for meniscal tears, 95% CI 12-113.6). Cartilage T2 values were higher in both tibial and medial femoral compartments in IL-ROA, but in IM-ROA were only significantly different from controls in the medial femur. CONCLUSION: IL-ROA knees show a greater prevalence and severity of MRI lesions and higher cartilage T2 values than IM-ROA knees compared with controls.

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.

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.

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.

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.

[An unusual case of non-traumatic enophthalmos]. / Ungewöhnlicher Fall eines atraumatischen Enophthalmus.

An extensive spectrum of differential diagnoses has to be considered when a patient presents with enophthalmos. The most common causes of this presentation include orbital trauma or contraction and atrophy of the orbital contents secondary to scleroderma or radiotherapy. However radiologists also have to consider less common causes of enophthalmos, such as the imploding antrum syndrome or the ethmoid silent sinus syndrome. The latter involves the ethmoidal cells and results in medial orbital wall implosion. Along with the case presentation the pathogenesis, incidence and differential diagnoses of ethmoid silent sinus syndrome are elucidated. In particular the differentiation from normal anatomical variants, such as dehiscent lamina papyracea is discussed.

Association of Physical Activity Measured by Accelerometer, Knee Joint Abnormalities, and Cartilage T2 Measurements Obtained From 3T Magnetic Resonance Imaging: Data From the Osteoarthritis Initiative.

OBJECTIVE: To study the cross-sectional association between physical activity measured with an accelerometer, structural knee abnormalities, and cartilage T2 values assessed with 3T magnetic resonance imaging (MRI). METHODS: We included 274 subjects from the Osteoarthritis Initiative cohort without definite radiographic osteoarthritis (Kellgren/Lawrence grades 0 and 1) and with at most mild pain, stiffness, and functional limitation in the study knee (Western Ontario and McMaster Universities Osteoarthritis Index scale 0-1), which had not limited their activity due to knee pain. Physical activity was measured over 7 days with an ActiGraph GT1M accelerometer. Subjects were categorized by quartile of physical activity based on the average daily minutes of moderate to vigorous physical activity (mv-PA). MRI images of the right knee (at 48-month visit) were assessed for structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) and for T2 relaxation times derived from segmented cartilage of 4 femorotibial regions and the patella. WORMS grades and T2 measurements were compared between activity quartiles using a linear regression model. Covariates included age, sex, body mass index, knee injury, family history of knee replacement, knee symptoms, hip and ankle pain, and daily wear time of the accelerometer. RESULTS: Higher mv-PA was associated with increased severity (P = 0.0087) and number of lesions of the medial meniscus (P = 0.0089) and with severity of bone marrow edema lesions (P = 0.0053). No association between cartilage lesions and mv-PA was found. T2 values of cartilage (loss, damage, and abnormalities) tended to be greater in the higher quartiles of mv-PA, but the differences were nonsignificant. CONCLUSION: In knees without radiographic osteoarthritis in subjects with no or mild knee pain, higher physical activity levels were associated with increases in meniscal and bone marrow edema pattern lesions.