Cartilage Degeneration In Patients Research Articles

Evaluation of articular cartilage degeneration in patients with osteonecrosis of the femoral head using T2 mapping magnetic resonance imaging.

To evaluate and characterise articular cartilage degeneration in patients with osteonecrosis of the femoral head (ONFH) using T2 mapping magnetic resonance imaging (MRI). We reviewed 35 patients with ONFH (20 males and 15 females, mean age 45.7±12.9 years) without obvious cartilage abnormalities on plain MRI (ONFH group) and 25 healthy volunteers (9 males and 16 females, mean age 42.9±5.8 years) (control group). All patients underwent T2 mapping MRI after ONFH onset. The region of interest was defined as the weight-bearing portion of the articular cartilage in the femoral head and acetabulum in the coronal view. The T2 values of the articular cartilage of the acetabulum and femoral head, including necrotic and normal regions, were significantly higher in the ONFH group than those in the control group. These T2 values of the acetabulum and femoral head in stages 3A and 2 were significantly higher in the ONFH group than those in the control group. The articular cartilage of the acetabulum and femoral head can deteriorate after the onset of ONFH, which may affect the natural history of ONFH and ONFH treatment. Our findings suggest the need for early intervention in joint preservation surgery.

Effects of Diclofenac Etalhyaluronate (SI-613/ONO-5704) on Cartilage Degeneration in Arthritic Rats and Inflammatory Cytokine-Stimulated Human Chondrocytes.

Cartilage degeneration is a key feature of osteoarthritis (OA) and rheumatoid arthritis and is thought to negatively impact patients' quality of life. Diclofenac etalhyaluronate (DEH, SI-613/ONO-5704) is a hyaluronic acid (HA) derivative chemically bound to diclofenac (DF) that has been reported to improve OA symptoms; however, its effect on cartilage degeneration remains unknown. In the present study, we investigated the chondroprotective effect of DEH in rats with collagen-induced arthritis and interleukin-1β-stimulated human chondrocytes. Rats with collagen-induced arthritis were administered DEH and HA intra-articularly, and DF orally. Knee joint swelling, histological scores of articular cartilage, and inflammatory (Il1b) and catabolic (Mmp3 and Mmp13) gene expression in the synovial tissue and cartilage were evaluated. In vitro direct effects of DEH on matrix metalloproteinase (MMP)-3 and MMP-13 expression were examined in interleukin-1β-stimulated human chondrocytes. In a rat model of collagen-induced arthritis, a single intra-articular dose of DEH inhibited knee joint inflammation and cartilage degeneration. Daily oral administration of DF had similar effects. Conversely, HA administered as a single intra-articular dose had no effect. Only DEH inhibited Mmp3 gene expression in the cartilage, whereas DEH and DF inhibited Mmp3 and Mmp13 mRNA expression in the synovial tissue. In interleukin-1β-stimulated human chondrocytes, DEH and HA inhibited MMP-3 and MMP-13 production, whereas DF had no effect. In this study, we demonstrated the chondroprotective effect of DEH in rats with collagen-induced arthritis and in interleukin-1β-stimulated human chondrocytes. Thus, DEH may suppress cartilage degeneration in patients with musculoskeletal diseases, such as OA.

Chronically elevated contact stress exposure correlates with intra-articular cartilage degeneration in patients with concurrent acetabular dysplasia and femoroacetabular impingement.

Hip dysplasia is known to lead to premature osteoarthritis. Computational models of joint mechanics have documented elevated contact stresses in dysplastic hips, but elevated stress has not been directly associated with regional cartilage degeneration. The purpose of this study was to determine if a relationship exists between elevated contact stress and intra-articular cartilage damage in patients with symptomatic dysplasia and femoroacetabular impingement. Discrete element analysis was used to compute hip contact stresses during the stance phase of walking gait for 15 patients diagnosed with acetabular dysplasia and femoral head-neck offset deformity. Contact stresses were summed over the duration of the walking gait cycle and then scaled by patient age to obtain a measure of chronic cartilage contact stress exposure. Linear regression analysis was used to evaluate the relationship between contact stress exposure and cartilage damage in each of six acetabular subregions that had been evaluated arthroscopically for cartilage damage at the time of surgical intervention. A significant correlation (R2 = 0.423, p < 0.001) was identified between chondromalacia grade and chronic stress-time exposure above both a 1 MPa damage threshold and a 2 MPa-years accumulated damage threshold. Furthermore, an over-exposure threshold of 15% regional contact area exceeding the 1 and 2 MPa-years threshold values resulted in correct identification of cartilage damage in 83.3% (55/66) of the acetabular subregions loaded during gait. These results suggest corrective surgery to alleviate impingement and reduce chronic contact stress exposures below these damage-inducing thresholds could mitigate further cartilage damage in patients with hip dysplasia.

Nano Drug Delivery Platforms for Dental Application: Infection Control and TMJ Management-A Review.

The oral cavity is an intricate environment subjected to various chemical, physical, and thermal injuries. The effectiveness of the local and systemically administered drugs is limited mainly due to their toxicities and poor oral bioavailability that leads to the limited effectiveness of the drugs in the target tissues. To address these issues, nanoparticle drug delivery systems based on metals, liposomes, polymeric particles, and core shells have been developed in recent years. Nano drug delivery systems have applications in the treatment of patients suffering from temporomandibular joint disorders such as preventing degeneration of cartilage in patients suffering from rheumatoid arthritis and osteoarthritis and alleviating the pain along with it. The antibacterial dental applications of nano-drug delivery systems such as silver and copper-based nanoparticles include these agents used to arrest dental caries, multiple steps in root canal treatment, and patients suffering from periodontitis. Nanoparticles have been used in adjunct with antifungals to treat oral fungal infections such as candida albicans in denture wearers. Acyclovir being the most commonly used antiviral has been used in combination with nanoparticles against an array of viral infections such as the herpes simplex virus. Nanoparticles based combination agents offer more favorable drug release in a controlled manner along with efficient delivery at the site of action. This review presents an updated overview of the recently developed nanoparticles delivery systems for the management of temporomandibular joint disorders along with the treatment of different oral infections.

Understanding Early Hemophilic Arthropathy in Children and Adolescents Through MRI T2 Mapping.

Persons with hemophilia experience hemarthrosis, which can lead to cartilage degeneration, causing physical impairment. MRI T2 mapping has the potential to be used as a tool to evaluate early arthropathic changes and cartilage degeneration in patients with hemophilia. To assess the value of MRI-T2 mapping as a tool for investigating the cartilage status of children and adolescents with hemophilic arthropathy. Prospective, cross-sectional. Twenty-eight boys with hemophilia (aged 5-17 years) and 23 healthy boys (aged 7-17 years). A multiecho spin-echo T2 -weighted gradient echo sequence was used on a 3.0T magnet. MRI-T2 maps of ankle (tibia-talus) (n = 19) or knee (femur-tibia) (n = 9) cartilage were assessed in hemophilia and healthy groups. An anatomically-based MRI score was also assigned to each ankle/knee. Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC), and analysis of variance (ANOVA) test. Negative associations between age and ankle/knee cartilage T2 relaxation times were found in hemophilia (r = -0.72 [P = 0.03] to -0.55 [P = 0.01]) and healthy (r = -0.84 [P < 0.001] to -0.55 [P = 0.20]) groups. There were nonsignificant associations between ankle cartilage T2 relaxation times and MRI scores (r = -0.15 [P = 0.54] to 0.31 [P = 0.19]). Results of this clinical investigation emphasize the potential importance of MRI-T2 maps as a tool to understand the functional status of cartilage in children and adolescents with hemophilic arthropathy, while holding promise for the detection of early cartilage degeneration prior to macroscopic characterization by conventional MRI. MRI-T2 mapping may provide novel information that is not reflected in the anatomically-based MRI scoring system. 3 TECHNICAL EFFICACY STAGE: 2.

Predictors of cartilage degeneration in patients with subchondral insufficiency fracture of the femoral head: a retrospective study

BackgroundThere is evidence that the cause of primary osteoarthritis (OA) is related to the changes in subchondral bone; however, the influence of subchondral insufficiency fracture (SIF) of the femoral head on the degeneration of the hip joint and the prognostic factors related to joint degeneration remain unclear. The objectives of this study were (1) to investigate the natural history of joint space width after the occurrence of SIF and (2) to investigate the associations between joint space narrowing and bone metabolic markers as well as magnetic resonance imaging (MRI) among the patients with SIF.MethodsBetween January 2010 and December 2019, 238 patients in whom band pattern of the femoral head were observed on MRI visited Hokkaido University Hospital. Among these patients, 44 hips in 41 patients were diagnosed with SIF and eligible for this retrospective study. We evaluated the joint space width (JSW) of the hip on the radiograph obtained at the first and last visits, length of the band lesion on MRI, bone mineral density by dual-energy X-ray absorptiometry, and bone metabolism markers. Similarly, the factors associated with the necessity of surgery and the progression of the narrowing of the joint space were evaluated.ResultsFifteen of the 44 hips required total hip arthroplasty (THA). A significant decrease was observed in the JSW from the first visit to the final follow-up. Changes in the JSW were associated with the length of band patterns, serum type 1 procollagen-N-propeptide (P1NP), and tartrate-resistant acid phosphatase 5b (TRACP-5b) during diagnosis. Additionally, bone metabolic markers tended to be associated with the length of the band pattern.ConclusionsSIF could cause joint space narrowing and hip OA. In addition to MRI findings as prognostic predictors of SIF, as previously described, bone metabolic markers were equally associated with changes in JSW, suggesting that these parameters could be useful in predicting the prognosis of SIF. Considering that bone metabolic markers trended to be associated with the length of band pattern, they might reflect the local severity.

Evaluation of humeral head cartilage using magnetic resonance imaging T1 rho mapping for patients with small-to-medium rotator cuff tears: A pilot study

BackgroundIt is unclear whether smaller rotator cuff tears cause cartilage degeneration. This study was designed to detect early humeral head cartilage degeneration in patients with small-to-medium cuff tears using magnetic-resonance-imaging T1 rho mapping. MethodsFive male and 5 female volunteers without shoulder symptoms (control group) and 5 male and 5 female patients with small-to-medium (<3 cm) rotator cuff tears underwent 3.0-T magnetic resonance imaging of a single shoulder. T1 rho values of the humeral head cartilage were measured and analyzed. ResultsThe total mean T1 rho value was 40.4 ± 3.4 ms for the control group and 45.0 ± 5.3 ms for the patient group. In the control group, the T1 rho values in the inferior articular cartilage were significantly higher than those in the superior and middle articular cartilage. In the patient group, there was no significant difference between all regions. A comparison between the patient and control groups showed that the mean T1 rho values in the superior-to-middle articular cartilage were significantly higher for the patient group than for the control group. However, in the inferior articular cartilage, there was no significant difference between both groups. ConclusionsThis study showed the possibility of early cartilage degenerative changes in the superior-to-middle humeral head articular cartilage of patients with small-to-medium rotator cuff tears.

Added Value of Preoperative Computed Tomography for Determining Cartilage Degeneration in Patients With Osteochondral Lesions of the Talar Dome

Background: Osteochondral lesions of the talar dome (OLTs) involve the articular cartilage and subchondral bone. The subchondral bone plate (SBP) plays a crucial role in cartilage metabolism, and computed tomography (CT) can provide more precise information on subchondral bone. CT image prediction of the histological findings on OLT will be useful to determine the most appropriate therapeutic strategy. Purpose: To evaluate the unique features of the CT findings that relate to the condition of the articular cartilage in OLT. Study Design: Cohort study; Level of evidence, 3. Methods: Thirty ankles in 29 patients who had OLT with an osteochondral fragment were retrospectively reviewed. At surgery, the osteochondral fragment of 19 ankles could be preserved (preservation group) by fixation or drilling, and in the remaining 11 ankles, the osteochondral fragment was removed (excision group). Preoperative CT findings were compared between the 2 groups. Biopsies of the osteochondral fragment from 13 ankles were performed. The relationship between the CT and histological findings were evaluated. Results: The area of lesion in the preservation group was significantly larger than that in the excision group. The CT images of the lesion showed the rate of absorption of the SBP in the preservation group to be lower than that in the excision group. As for the lesion bed absorption, it was higher in the preservation group than in the excision group. All cases in the excision group showed bed sclerosis, compared with 42.1% in the preservation group. The specimens with disruption of the SBP exhibited cartilage degeneration and abundant chondrocyte cloning. OLT with absorption of the SBP on CT showed severe cartilage degeneration, while the remaining SBP on CT showed low-grade cartilage degeneration. Conclusion: This study shows the features of preoperative CT and histological findings in OLT with osteochondral fragments. The condition of the SBP affects the cartilage degeneration. CT findings provide important information for the determination of surgical treatment.

Coenzyme Q10 Prevents the Interleukin-1 Beta Induced Inflammatory Response via Inhibition of MAPK Signaling Pathways in Rat Articular Chondrocytes.

Preclinical Research Osteoarthritis (OA) is a widely prevalent degenerative joint disease that severely impairs the health of the elderly population resulting in a heavy economic burden worldwide. Coenzyme Q10 (CoQ10) has shown anti-inflammatory effects in some diseases. The present study aimed to investigate if CoQ10 would suppress catabolic responses of interleukin (IL)-1β-induced chondrocytes. Rat chondrocytes were cultured and pretreated with CoQ10, and then stimulated with or without IL-1β (10 ng/ml). The expression and production of matrix metalloproteinase (MMP)-3, MMP-9, and MMP13 were determined using real-time PCR and Western blotting. CoQ10 suppressed MMP-3, MMP-9, and MMP13 production induced by IL-1β, and markedly inhibited IL-1β-induced MAPK pathways in rat chondrocytes. The present study provides insight into potential mechanisms by which CoQ10 protects against degeneration of cartilage in patients with OA, which may lead to new approaches for the treatment of OA.Drug Dev Res 78 : 403-410, 2017. © 2017 Wiley Periodicals, Inc.

Severe cartilage degeneration in patients with developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a developmental disorder that has long-term chronic pain and limited hip joint mobility as major pathological characteristics. This study aims to access the association between the development of DDH and cartilage metabolic disorders. Cartilage tissue samples were acquired from patients with DDH, osteoarthritis (OA) and femoral neck fracture. The proteoglycan level was evaluated by safranin O-fast green, toluidine blue and hematoxylin-eosin (HE) staining. The levels of collagen-II (Col-II), collagen-X (Col-X) and metal matrix proteinase-13 (MMP-13) were evaluated by immunohistochemistry (IHC) and Western blotting analysis. The morphologic evaluation of cartilage was conducted by transmission electron microscopy (TEM). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA level of aggrecan, Col-II, Col-X and MMP-13. The aggrecan level in the cartilage matrix was significantly decreased in DDH patients by safranin O-fast green and toluidine blue staining in comparison with that in the OA and control groups. In contrast with the OA group, the Col-II expression was reduced while the MMP-13 expression increased in DDH patients, as shown by IHC and Western blotting analysis. The collagenous fibrils in cartilage of DDH patients appeared significantly sparse and disordered in the TEM analysis. In DDH patients, the mRNA expression levels of Col-II and aggrecan were markedly reduced, while the mRNA expression of Col-X was markedly increased, compared with the OA patients. There is severe articular cartilage degeneration in DDH patients. This observation provides us with new insight into cartilage metabolic regulation in DDH. © 2017 IUBMB Life, 69(3):179-187, 2017.

Composite metric R2 - R1ρ (1/T2 - 1/T1ρ ) as a potential MR imaging biomarker associated with changes in pain after ACL reconstruction: A six-month follow-up.

This study looked to investigate a new quantitative metric, R2 - R1ρ (1/T2 - 1/T1ρ ), using magnetic resonance (MR) images and voxel-based relaxometry (VBR) for detecting early cartilage degeneration and explore the association with patient-reported outcomes measures (PROMs) in patients 6 months after ACL reconstruction. Sixty-four patients from three sites were bilaterally scanned on a 3T MR with a combined T1ρ /T2 protocol to calculate R1ρ (1/T1ρ ) and R2 (1/T2 ) values at baseline and 6 months after reconstructive surgery. Non-rigid registration was applied to align images onto a template, allowing VBR to determine VBR rate differences and explore cross-sectional and longitudinal differences between injured and uninjured knees, generating Statistical Parametric Maps (SPMs). Baseline R2 - R1ρ differences were further correlated with change in PROMs from the Knee Injury and Osteoarthritis Outcome Score (KOOS) from baseline to 6 months. Cross-sectional results demonstrated low relaxation rate differences in the injured patella (baseline: 21%, p = 0.01; 6-months: 18%, p = 0.02), lateral tibia (baseline: 25%, p = 0.01; 6-months: 24%, p = 0.01), and weight-bearing regions of the tibia and femur. The uninjured patella showed significant longitudinal changes (17%, p = 0.02). R2 - R1ρ differences showed significant correlations with KOOS PROMs, particularly in the lateral tibia, patella, and trochlea. R2 - R1ρ difference VBR analyses provide new and highly sensitive parameters for assessing early cartilage degeneration in patients after ACL injury by integrating findings from both T1ρ and T2 , commonly used relaxation time parameters, into a single metric. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:718-729, 2017.

Prospective In Vivo Comparison of Damaged and Healthy-Appearing Articular Cartilage Specimens in Patients With Femoroacetabular Impingement: Comparison of T2 Mapping, Histologic Endpoints, and Arthroscopic Grading

To describe T2 mapping values in arthroscopically determined International Cartilage Repair Society (ICRS) grades in damaged and healthy-appearing articular cartilage waste specimens from arthroscopic femoroacetabular impingement (FAI) treatment. Furthermore, we sought to compare ICRS grades of the specimens with biochemical, immunohistochemistry and histologic endpoints and assess correlations with T2 mapping. Twenty-four patients were prospectively enrolled, consecutively, between December 2011 and August 2012. Patients were included if they were aged 18years or older and met criteria that followed the clinical indications for arthroscopy to treat FAI. Patients with prior hip trauma including fracture or dislocation or who have undergone prior hip surgery were excluded. All patients received a preoperative sagittal T2 mapping scan of the hip joint. Cartilage was graded intraoperatively using the ICRS grading system, and graded specimens were collected as cartilage waste for histologic, biochemical, and immunohistochemistry analysis. Forty-four cartilage specimens (22 healthy-appearing, 22 damaged) were analyzed. Median T2 values were significantly higher among damaged specimens (55.7 ± 14.9ms) than healthy-appearing specimens (49.3 ± 12.3ms; P= .043), which was most exaggerated among mild (grade 1 or 2) defects where the damaged specimens (58.1 ± 16.4ms) were significantly higher than their paired healthy-appearing specimens (48.7 ± 15.4ms; P=.026). Severely damaged specimens (grade 3 or 4) had significantly lower cumulative H&E than their paired healthy-appearing counterparts (P= .02) but was not statistically significant among damaged specimens with mild (grade 1 or 2) defects (P= .198). Among healthy-appearing specimens, median T2 and the percentage of collagen fibers oriented parallel were significantly correlated (rho= 0.425, P= .048). This study outlines the potential for T2 mapping to identify early cartilage degeneration in patients undergoing arthroscopy to treat FAI. Findings in ICRS grade 1 and 2 degeneration corresponded to an increase in T2 values. Further biochemical evaluation revealed a significant difference between healthy-appearing cartilage and late degeneration in cumulative H&E as well as significantly lower percentage of collagen fibers oriented parallel and a higher percentage of collagen fibers oriented randomly when considering all grades of cartilage damage. Level II, prospective comparative study.

Corticosteroids and low bone mineral density affect hip cartilage in systemic lupus erythematosus patients: Quantitative T2 mapping

The purpose of this diagnostic study was to quantify the effect of high-dose corticosteroid treatment on hip joint cartilage degeneration in patients with systemic lupus erythematosus (SLE), with and without osteonecrosis, using magnetic resonance imaging (MRI). T2 mapping, with a 3.0 Tesla Discovery MR750 (GE Healthcare) MRI scanner, was performed in 12 volunteers without hip pathology (control group, 12 hips), in 11 patients with SLE without osteonecrosis, who were receiving corticosteroid therapy (corticosteroid-ON group, 17 hips), and in 15 patients with SLE receiving corticosteroids, who had noncollapsed and asymptomatic osteonecrosis (corticosteroid+ON group, 26 hips). The distribution of T2 values in the femoral head and acetabular cartilage were compared among the three groups. Step-wise multiple regression analysis was performed to determine the prognostic factors for T2 values indicative of femoral head cartilage degeneration. Mean T2 values of femoral head cartilage were significantly higher in the corticosteroid-ON (40.3 ms) and corticosteroid+ON (35.2 ms) groups than in the control group (30.1 ms, P = 0.001). T2 values of acetabular cartilage were significantly higher in the corticosteroid-ON group (41.8 ms) versus the control (33.4 ms) and the corticosteroid+ON groups (37.0 ms; P = 0.001). Low bone mineral density was a significant prognostic factor for high T2 values of cartilage at the femoral head in patients treated with corticosteroids, regardless of whether they had osteonecrosis. T2 mapping suggests that corticosteroid therapy and osteoporosis are independent risk factors for cartilage degeneration at the femoral head in patients with SLE.

Synovial Fluid α-MSH Levels are Inversely Correlated with Articular Cartilage Degeneration in Anterior Cruciate Ligament Deficient Knees.

Secondary osteoarthritis after ligament or meniscus injury generally causes great burdens to patients. Alpha-melanocyte-stimulating hormone (α-MSH ), a 13 amino acid neuropeptide produced by intracellular cleavage of the proopiomelanocortin (POMC) hormone, has been proven to suppress inflammation and protect cartilage from damage. The present study was carried out to explore the relationship between synovial fluid α-MSH levels and articular cartilage degeneration in patients with anterior cruciate ligament (ACL) deficiency. 51 patients with ACL deficiency admitted to our hospital were enrolled. The Noyes score method was used to assess articular cartilage damage arthroscopically. Synovial fluid α-MSH levels were examined using a double antibody radioimmunoassay method. Inflammation markers such as IL-6, MMP-3, and degradation biomarker of collagen type II (CTX-II) were also explored by enzyme-linked immunosorbent assay (ELISA). The articular cartilage in ACL deficiency patients deteriorated significantly with time after injury (r = 0.673, p < 0.001). Synovial fluid α-MSH levels are inversely associated with Noyes scores (r = -0.682, p < 0.001), levels of inflammation markers IL-6 (r = -0.302, p = 0.035), MMP-3 (r = -0.652, p < 0.001) and degradation biomarker CTX-II (r = -0.584, p < 0.001). Synovial fluid α-MSH levels showed an independent and negative correlation with articular cartilage degeneration in patients with knee ACL deficiency. Supplementing with a-MSH may serve as a possible adjuvant therapy for delaying cartilage degeneration after ACL injury.

Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group

ObjectiveThe aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methodsSagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. ResultsThere were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ=0.737 and ρ=0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. ConclusionsOur study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.

T2 relaxation times of the glenohumeral joint at 3.0 T MRI in patients with and without primary and secondary osteoarthritis.

Quantitative magnetic resonance imaging (MRI) of cartilage has recently been applied to patients with osteoarthritis (OA). T2 mapping is a sensitive method of detecting changes in the chemical composition and structure of cartilage. To establish baseline T2 values of glenohumeral joint cartilage at 3.0 T and compare T2 values among subjects with and without OA. The study involved 30 patients (18 women, 12 men; median age, 67 years; age range, 51-78 years) with primary (n = 7) and secondary OA (n = 23) in the glenohumeral joint and 34 subjects without OA (19 women, 15 men; median age, 49 years; age range, 23-63 years). All subjects were evaluated by radiography and 3.0 T MRI including a multi-echo T2-weighted spin echo pulse sequence. The T2 value of the cartilage was measured by manually drawing the region of interest on the T2 map. Per-zone comparison of T2 values was performed using Mann-Whitney U test. Median T2 values differed significantly between subjects without OA (36.00 ms [interquartile range, 33.89-37.31 ms]) and those with primary (37.52 ms [36.84-39.11], P = 0.028), but not secondary (36.87 ms [34.70-41.10], P = 0.160) OA. Glenohumeral cartilage T2 values were higher in different zones between patients with primary and secondary OA than in subjects without OA. These T2 values can be used for comparison to assess cartilage degeneration in patients with shoulder OA. Significant differences in T2 were observed among subjects without OA and those with primary and secondary OA.

Alterations in the chondroitin sulfate chain in human osteoarthritic cartilage of the knee

To determine whether the structure of chondroitin sulfate (CS) in cartilage is reflected by the degree of cartilage degeneration in patients with osteoarthritis (OA) of the knee and to determine how CS biosynthesis affects cartilage degeneration. Two osteoarthritic cartilage samples were obtained from medial femoral condyle (MFC) and lateral femoral condyle (LFC) of 24 knees with end-stage OA. The samples were assigned to two groups as follows: lesion and remote cartilage were adjacent to and remote from the osteoarthritic cartilage, respectively. Histological grade was determined according to the Mankin score. The CS concentration and chain length were determined using high-performance liquid chromatography (HPLC) and gel filtration chromatography, respectively. Expression of the gene encoding CS glycosyltransferase was evaluated using a real-time quantitative polymerase chain reaction (qPCR) assay. These results were compared between lesion and remote cartilage. The Mankin score indicated that lesion cartilage was more degraded compared with remote cartilage. Although the CS levels varied among individuals, the mean CS concentration and chain length were significantly lower and shorter in lesion cartilage than in remote cartilage, respectively (concentration: 12.04 vs 14.84 μg/mg wet weight, P = 0.021; chain length: 5.36 vs 6.19 kDa, P = 0.026). Three genes encoding CS glycosyltransferases (CHPF, CSGALNACT1, CSGALNACT2) were expressed at lower levels in lesion cartilage. In the osteoarthritic knee, the CS concentration and chain length were reduced closer to the more degraded cartilage with decreasing CS glycosyltransferase gene expression. Inhibition of CS glycosyltransferase gene expression may reduce CS chain length, which may contribute to OA progression.

T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of glenohumeral cartilage in asymptomatic volunteers at 3 T

To establish baseline T2* and T1Gd values of glenohumeral cartilage at 3 T. Forty asymptomatic volunteers (mean age: 24.8 ± 2.2 years) without shoulder abnormalities were included. The MRI protocol comprised a double-echo steady-state (DESS) sequence for morphological cartilage evaluation, a gradient-echo multiecho sequence for T2* assessment, and a gradient-echo dual-flip-angle sequence for T1Gd mapping. Statistical assessment involved a one-way analysis of variance (ANOVA) to identify the differences between various regions of the glenohumeral joint and intraclass correlation (ICC) analysis comparing repetitive T2* and T1Gd measures to assess intra- and interobserver reliability. Both techniques revealed significant differences between superior and inferior glenohumeral cartilage demonstrating higher T2* (26.2 ms vs. 23.2 ms, P value < 0.001) and T1Gd (750.1 ms vs. 720.2 ms, P value = 0.014) values in the superior regions. No trend was observed in the anterior-posterior measurement (P value range: 0.279-1.000). High intra- and interobserver agreement (ICC value range: 0.895-0.983) was noted for both T2* and T1Gd mapping. T2* and T1Gd mapping are reliable in the assessment of glenohumeral cartilage. The values from this study can be used for comparison to identify cartilage degeneration in patients suffering from shoulder joint abnormalities. • T2* mapping and dGEMRIC are sensitive to collagen degeneration and proteoglycan depletion. • This study aimed to establish baseline T2*/dGEMRIC values of glenohumeral cartilage. • Both techniques revealed significant differences between superior and inferior glenohumeral cartilage. • High intra-/interreader agreement was noted for both T2* mapping and dGEMRIC. • These baseline normal values should be useful when identifying potential degeneration.

A fully automated system for quantification of knee bone marrow lesions using MRI and the osteoarthritis initiative cohort

Background/Objective: Bone marrow lesions (BMLs) have been associated with pain and cartilage degeneration in patients with knee osteoarthritis; their specific detection and quantification is therefore of primary importance. This study aimed at developing a fully automated quantitative BML assessment technology for human knee osteoarthritis using magnetic resonance images (MRI) and two sequences, a T1/T2*-weighted gradient echo (DESS) and a water-sensitive intermediate-weighted turbo spin echo (IW-TSE). Methods: The automated BML quantification first characterizes the bone and cartilage domains in the DESS sequence using our already published automated technology, then proceeds to the BML quantification which was developed as a four-stage process: selection of structured bright areas corresponding to BMLs, geometric filtering of unrelated structures, segmentation of the BML, and quantification of BML proportion within bone regions. For the IW-TSE sequence, the first step consists of the transfer of the bone and cartilage objects from the DESS to the IW-TSE images, followed by the BML detection and quantification as for the DESS. Validation was performed on 154 OA patients from a subset of the Osteoarthritis Initiative (OAI) cohort (public data sets) in which BML manual segmentation intra- and inter-reader reliability was done for each sequence (DESS and IW-TSE) using the intraclass correlation (ICC). BML comparison between the newly developed automated method with a manual segmentation was performed with ICC for the proportion of BML and Dice similarity coefficient (DSC) for BML localization and geometric extent. Finally, comparisons between the DESS and the IW-TSE sequences were performed for BML incidence and proportion. Results: Excellent to very good correlations were obtained for both MRI sequences for intra- and inter-reader reliability of the manual BML segmentation. Comparison between the developed automated method and the manual BML segment- ation showed excellent to very good correlations in the global knee and regions (ICC=0.99 to 0.68 for DESS and 0.99 to 0.77 for IW-TSE sequences) as well as very good to good similarity for the BML geometrical agreement (DESS, 0.60 to 0.41; IW-TSE, 0.59 to 0.41). Data revealed greater BML incidence at the sites of high articular constraints: lateral femoropatellar and medial tibiofemoral articulation. Average BML proportion revealed a scaling factor of about 4.5-fold more for the IW-TSE compared to the DESS. Conclusions: The newly developed fully automated MRI based BML assessment technology not only detects the absence/ presence of these pathological signals in the osteoarthritic human knee, but also provides accurate quantitative assessment of BMLs in the global knee and knee regions. Such automated system will enable large scale studies to be conducted within shorter durations, as well as increase stability of the reading.

Highly sensitive ELISA for determining serum keratan sulphate levels in the diagnosis of OA

There have been a large number of reports on alterations in the serum level of keratan sulphate (KS), a potential marker of articular cartilage degeneration in patients with arthropathy. Such studies have commonly employed ELISA using the anti-KS monoclonal antibody 1/20/5D4 (5D4-ELISA) to determine KS levels. Recently, a highly sensitive KS ELISA (HS-ELISA) kit has been developed, allowing determination of serum KS levels even in small animals, which were formerly undetectable with 5D4-ELISA. However, the effectiveness of this kit in humans has not been demonstrated. The objective of this study was to assess the usefulness of the HS-ELISA for the analysis of human serum samples. Serum samples were collected from 28 patients with knee OA and 23 healthy volunteers. KS was determined by 5D4-ELISA and HS-ELISA, and measurements were compared with those obtained by HPLC. KS levels in serum samples with protease pretreatment were also determined by HS-ELISA. KS levels determined by HS-ELISA exhibited a better correlation with those determined by HPLC, and a higher diagnostic sensitivity for OA compared with 5D4-ELISA. Protease pretreatment of serum further improved the correlation between the values obtained by HS-ELISA and HPLC, as well as the diagnostic sensitivity of HS-ELISA for OA. HS-ELISA proved useful for determining KS level in serum and the diagnosis of OA. Pretreatment of serum samples with a protease further improved the performance of HS-ELISA.