Osteoarthritis Research Society International Grading Research Articles

Intra-articular Injection of Chloramphenicol Reduces Articular Cartilage Degeneration in a Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Studies have found that enhancement of autophagy, an intracellular catabolic process, may limit the pathologic progression of OA. Chloramphenicol is a potent activator of autophagy; however, the effects of chloramphenicol on articular cartilage are unknown. Using human OA knee chondrocytes in vitro, we asked, does chloramphenicol (1) activate autophagy in chondrocytes; (2) protect chondrocytes from IL-1β-induced apoptosis; and (3) reduce the expression of matrix metallopeptidase (MMP)-13 and IL-6 (markers associated with articular cartilage degradation and joint inflammation). Using an in vivo rabbit model of OA, we asked, does an intra-articular injection of chloramphenicol in the knee (4) induce autophagy; (5) reduce OA severity; and (6) reduce MMP-13 expression? Human chondrocytes were extracted from 10 men with OA undergoing TKA. After treatment with 25 μg/mL, 50 μg/mL, or 100μg/mL chloramphenicol, the autophagy of chondrocytes was detected with Western blotting, transmission electron microscopy, or an autophagy detection kit. There were four groups in our study: one group was untreated, one was treated with 100 μg/mL chloramphenicol, another was treated with 10 ng/mL of IL-1β, and the final group was treated with 10 ng/mL of IL-1β and 100 μg/mL of chloramphenicol. All groups were treated for 48 hours; cell apoptosis was detected with Western blotting and flow cytometry. Inflammation marker IL-6 in the cell culture supernatant was detected with an ELISA. Articular cartilage degradation-related enzyme MMP-13 was analyzed with Western blotting. A rabbit model of OA was induced by intra-articular injection of type II collagenase in 20 male 3-month-old New Zealand White rabbits' right hind leg knees; the left hind leg knees served as controls. Rabbits were treated by intra-articular injection of saline or chloramphenicol once a week for 8 weeks. Autophagy of the articular cartilage was detected with Western blotting and transmission electron microscopy. Degeneration of articular cartilage was analyzed with Safranin O-fast green staining and the semi-quantitative index Osteoarthritis Research Society International (OARSI) grading system. Degeneration of articular cartilage was evaluated using the OARSI grading system. The expression of MMP-13 in articular cartilage was detected with immunohistochemistry. Chloramphenicol activated autophagy in vitro in the chondrocytes of humans with OA and in an in vivo rabbit model of OA. Chloramphenicol inhibited IL-1-induced apoptosis (flow cytometry results with chloramphenicol, 25.33 ± 3.51%, and without chloramphenicol, 44.00 ± 3.61%, mean difference, 18.67% [95% CI 10.60 to 26.73]; p = 0.003) and the production of proinflammatory cytokine IL-6 (ELISA results, with chloramphenicol, 720.00 ± 96.44 pg/mL, without chloramphenicol, 966.67 ± 85.05 pg/mL; mean difference 74.24 pg/mL [95% CI 39.28 to 454.06]; p = 0.029) in chondrocytes. After chloramphenicol treatment, the severity of cartilage degradation was reduced in the treatment group (OARSI 6.80 ± 2.71) compared with the control group (12.30 ± 2.77), (mean difference 5.50 [95% CI 1.50 to 9.50]; p = 0.013). Furthermore, chloramphenicol treatment also decreased the production of MMP-13 in vitro and in vivo. Chloramphenicol reduced the severity of cartilage degradation in a type II collagen-induced rabbit model of OA, which may be related to induction of autophagy and inhibition of MMP-13 and IL-6. Our study suggests that an intra-articular injection of chloramphenicol may reduce degeneration of articular cartilage and that induction of autophagy may be a method for treating OA. The animal model we used was type II collagen-induced OA, which was different from idiopathic OA and post-traumatic OA. Therefore, we need to use other types of OA models (idiopathic OA or a surgically induced OA model) to further verify its effect, and the side effects of chloramphenicol also need to be considered, such as myelosuppression.

Predictors of Radiographic Osteoarthritis 2 to 3 Years After Anterior Cruciate Ligament Reconstruction: Data From the MOON On-site Nested Cohort.

Background:Multiple studies have shown that patients are susceptible to posttraumatic osteoarthritis (PTOA) after an anterior cruciate ligament (ACL) injury, even with ACL reconstruction (ACLR). Prospective studies using multivariable analysis to identify risk factors for PTOA are lacking.Purpose/Hypothesis:This study aimed to identify baseline predictors of radiographic PTOA after ACLR at an early time point. We hypothesized that meniscal injuries and cartilage lesions would be associated with worse radiographic PTOA using the Osteoarthritis Research Society International (OARSI) atlas criteria.Study Design:Cohort study; Level of evidence, 3.Methods:A total of 421 patients who underwent ACLR returned on-site for standardized posteroanterior semiflexed knee radiography at a minimum of 2 years after surgery. The mean age was 19.8 years, with 51.3% female patients. At baseline, data on demographics, graft type, meniscal status/treatment, and cartilage status were collected. OARSI atlas criteria were used to grade all knee radiographs. Multivariable ordinal regression models identified baseline predictors of radiographic OARSI grades at follow-up.Results:Older age (odds ratio [OR], 1.06) and higher body mass index (OR, 1.05) were statistically significantly associated with a higher OARSI grade in the medial compartment. Patients who underwent meniscal repair and partial meniscectomy had statistically significantly higher OARSI grades in the medial compartment (meniscal repair OR, 1.92; meniscectomy OR, 2.11) and in the lateral compartment (meniscal repair OR, 1.96; meniscectomy OR, 2.97). Graft type, cartilage lesions, sex, and Marx activity rating scale score had no significant association with the OARSI grade.Conclusion:Older patients with a higher body mass index who have an ACL tear with a concurrent meniscal tear requiring partial meniscectomy or meniscal repair should be advised of their increased risk of developing radiographic PTOA. Alternatively, patients with an ACL tear with an articular cartilage lesion can be reassured that they are not at an increased risk of developing early radiographic knee PTOA at 2 to 3 years after ACLR.

Predictors of Radiographic Osteoarthritis 2-3 Years after ACL Reconstruction: Data from MOON Onsite Nested Cohort

Objectives: Multiple studies have shown patients are susceptible to post-traumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury even with ACL reconstruction (ACLR). Prospective studies using multivariate analysis to identify risk factors for PTOA are lacking. This study aims to identify baseline predictors of radiographic PT OA after ACLR at an early time point and hypothesizes that meniscal injury and cartilage lesions will be associated with worse radiographic OA using the Osteoarthritis Research Society International (OARSI) atlas criteria. Methods: 421 patients who underwent ACLR returned onsite for standardized posteroanterior metatarsophalangeal radiographs a minimum of 2 years after surgery. At baseline, demographics, graft type, meniscal status/treatment, and cartilage status were collected. OARSI atlas criteria were used to grade all knee radiographs. Multivariable ordinal regression models identified baseline predictors of radiographic OARSI grades at follow-up. Results: The mean age was 19.8 years with 51.3% females. Higher age (odds ratio (OR) 1.06) and BMI (OR 1.05) were statistically significantly associated with higher OARSI grade in the medial compartment. Patients with a meniscal repair and a partial meniscectomy had statistically significantly higher OARSI grades in the medial compartment (meniscal repair OR 1.92 and meniscectomy OR 2.11) and in the lateral compartment (meniscal repair OR 1.96 and meniscectomy OR 2.97). Graft type, cartilage lesion, sex, and Marx activity scales had no significant association with OARSI grade. Conclusion: Older patients with a higher BMI who have an ACL tear with concurrent meniscal tear requiring partial meniscectomy or meniscal repair should be advised of their increased risk of developing radiographic OA. Alternatively, patients with an ACL tear with an articular cartilage lesion can be reassured that they are not at increased risk of developing radiographic knee OA at 2-3 years following ACLR.

The role of intra-articular administration of Fetuin-A in post-traumatic knee osteoarthritis: an experimental study in a rat model

BackgroundThe purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic secondary osteoarthritis in rats, and also its effect on the systematic levels of interleukins (ILs)-2,4,7, bone morphogenetic proteins (BMPs) 2, 4, 7, C-Reactive Protein (CRP) and Fetuin-A.MethodsThirty male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only the surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly, intra-operatively. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Osteoarthritic lesions of the knee were classified according to the Osteoarthritis Research Society International Grading System and the Modified Mankin Score, by histologic examination.ResultsIL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance.ConclusionsIntra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group.

Through-thickness patterns of shear strain evolve in early osteoarthritis

Given the structural changes associated with the progression of Osteoarthritis (OA), we hypothesized that patterns of through-thickness, large-strain shear evolve with early-stage OA. We therefore aimed to determine whether and how patterns of shear strains change during early-stage OA to 1) gain insight into the progression of OA by quantifying changes in local deformations; 2) gauge the potential of patterns in shear strain to serve as image-based biomarkers of early-stage OA; and 3) provide high-resolution, through-thickness data for proposing, fitting, and validating constitutive models for cartilage. We completed displacement-driven, large-strain shear tests (5, 10, 15%) on 44 specimens of variably advanced osteoarthritic human articular cartilage as determined by both Osteoarthritis Research Society International (OARSI) grade and PLM-CO score. We recorded the through-thickness deformations with a stereo-camera system and processed these data using digital image correlation (DIC) to determine full-thickness patterns of strains and relative zonal recruitments, i.e., the average shear strain in a through-thickness zone weighted by its relative thickness and normalized by the applied strain. We observed three general shapes for the curves of averaged through-thickness, Green-Lagrange shear strains during progression of OA. We also observed that during the progression of OA only the deep zone is recruited differently under shear in a statistically significant way. We propose that changes in through-thickness patterns of shear strain could provide sensitive biomarkers for early clinical detection of OA. The relative zonal recruitment of the deep zone decreases with progressing OA (OARSI grade) and microstructural remodeling (PLM-CO score), which do not consistently affect recruitment of the superficial and middle zones.

VEGF-A is associated with early degenerative changes in cartilage and subchondral bone

Paired cartilage and subchondral bone of subjects with no clinical history of joint disorders were analyzed to determine whether antioxidant enzymes, inflammatory cytokines and growth factors can be linked to a pre-osteoarthritis. Tissue explants were phenotyped according to Osteoarthritis Research Society International grading and micro-computed tomography, and also screened for the expression of several markers using quantitative polymerase chain reaction. The expression of these same genes was measured in SW1353 cells treated with hydrogen peroxide, to gain insight into the pathways involved with oxidative stress responses. Vascular endothelial growth factor A (VEGF-A) was up-regulated in the cartilage samples that showed early cartilage or bone degeneration. Oxidative stress in chondrocytes provoked up-regulation of interleukin-1β, interleukin-6, aggrecan, and SRY-box containing gene 9. Our results confirm the hitherto evidence of the deteriorating effects of the oxidative stress on cartilage and suggest the link between VEGF-A and pre-osteoarthritis.

Thickness of the bone-cartilage unit in relation to osteoarthritis severity in the human hip joint

ObjectiveBone formation is a hallmark of osteoarthritis (OA). It has been speculated that bone formation may occur because of ossification at the bone-cartilage unit, that is, bone formation directly involving...

Comparison of Cytotoxic Effects of Intra-Articular Use of Tranexamic Acid versus Epinephrine on Rat Cartilage.

BackgroundAdequate visualization is known to be essential to perform arthroscopic procedures effectively and efficiently. We hypothesized that tranexamic acid may be considered as an alternative agent to reduce intra-articular bleeding during arthroscopic procedures, after comparing its potential chondrotoxicity with that of epinephrine.Material/MethodsSeventy-two rats were randomized into 3 groups with 24 rats each. The injections were performed in the right knees, as follows: Group 1: 0.25 mL of tranexamic acid solution, Group 2: 0.25 mL of epinephrine solution, and Group 3: 0.25 mL of 0.9% saline, serving as control. One week after the injections, the animals were euthanized. Samples were evaluated histologically based on the Osteoarthritis Research Society International (OARSI) Histopathology Grading and Staging System and the “live/dead” staining technique to determine chondrocyte viability.ResultsComparison of epinephrine and tranexamic acid revealed significantly higher OARSI scores in the epinephrine group (epinephrine: 3.42±1.31, TA: 0.92±0.90; P<0.001). The most significant difference between the 2 groups was in the number of joints diagnosed with OARSI grade III. The percentage of viability was significantly higher in the tranexamic acid group when compared with the epinephrine group (tranexamic acid: 79.74±3.343; epinephrine: 63.81±1.914; P<0.05).ConclusionsBased on the histologic parameters and chondrocyte viability, tranexamic acid is less cytotoxic than epinephrine in rat chondrocytes at the doses typically used in irrigation fluid, and may be a good alternative to epinephrine in arthroscopic surgery.

Viability and Tissue Quality of Cartilage Flaps From Patients With Femoroacetabular Hip Impingement: A Matched-Control Comparison.

Background:Chondrolabral damage is commonly observed in patients with cam-type femoroacetabular impingement (FAI). Chondral flap reattachment has recently been proposed as a possible preservation technique.Purpose/Hypothesis:The purpose of this study was to determine the viability and tissue quality of chondral flaps from patients with FAI at the time of arthroscopy. It was hypothesized that chondral flaps from patients with cam lesions of the hip would exhibit less viability and greater tissue degeneration than would those of a matched control group.Study Design:Cohort study; Level of evidence, 2.Methods:Patients with cam-type FAI who were treated with hip arthroscopy between 2014 and 2016 were asked to participate in this study. The cartilage lesions were localized and classified intraoperatively according to Beck classification. A chondral flap (study group) and a cartilage sample (control group) were obtained from each patient for histologic evaluation. Cellular viability and tissue quality were examined and compared in both groups. Cellular viability was determined with live/dead staining, and tissue quality was evaluated using safranin O/fast green, hematoxylin and eosin (H&E) staining, and immunohistochemistry for collagen II. Osteoarthritis Research Society International (OARSI) grading was used for quality assessment, and Image J software was used to calculate the percentage of tissue viability and Col II stain.Results:A total of 10 male patients with a mean age of 38.4 years (range, 30-55 years) were enrolled. All chondral flaps were classified as Beck grade 4. The mean cellular viability of the chondral flaps was reduced (54.6% ± 25.6%), and they were found to be degenerated (OARSI grade, 4 ± 1.27). Control samples also had reduced viability (38.8% ± 30.3%) and were degenerative (OARSI grade, 3.5 ± 1.38). There was no statistically significant intergroup difference for viability (P = .203) or OARSI grade (P = .645), nor was there an intragroup correlation between viability and OARSI grade (P > .05). A significant negative correlation (r = −0.9, P = .035) was found between OARSI grade and collagen II percentage scale in 5 selected samples.Conclusion:Despite appearing normal macroscopically, the chondral flaps from patients with cam-type FAI displayed loss of viability and tissue degeneration. In addition, control samples obtained away from the injury area also displayed cartilage damage and degeneration. Careful consideration should be taken when attempting to reattach the chondral flap.

Histological Features of the Distal Third Metacarpal Bone in Thoroughbred Racehorses, With and Without Lateral Condylar Fractures

A detailed histopathological study of the distal third metacarpal bone of Thoroughbred racehorses was undertaken to characterize lesions observed previously on magnetic resonance imaging (MRI). The bones were selected and grouped on the basis of MRI features. Representative sections in different planes were processed for histopathology. All lesions observed in the articular cartilage (AC) and subchondral bone (SCB) were recorded and graded with a scoring system, based partially on the Osteoarthritis Research Society International grading system. The scoring system included the severity of the lesion. Descriptive statistics and linear mixed effects models were performed. A positive correlation was observed between the severity of histopathological changes in the superficial and deeper osteochondral tissues, and between the number of race starts and AC score. Age was not correlated with AC or SCB score. A moderate variation in AC and SCB scores was observed between the groups; however, there were differences within individual bones. Bones with focal palmar necrosis (FPN) showed significant differences in the histological scoring of the AC compared with bones without FPN. Bones with incomplete fractures or larger areas of bone remodelling showed significant differences in SCB pathology when compared with bones with FPN. Haematoidin was detected in areas with excessive SCB and cancellous bone sclerosis and/or irregular bone density. This finding is suggestive of poor blood perfusion in these areas.

Different doses of strontium ranelate and mechanical vibration modulate distinct responses in the articular cartilage of ovariectomized rats.

To investigate the effects of different strontium ranelate (SrR) doses alone or in combination with low-intensity and high-frequency mechanical vibration (MV) on articular cartilage in ovariectomized rats. Fifty 6-month-old female Wistar rats underwent ovariectomy (OVX) and after 3months were divided into: control group (Control); SrR 300mg/kg/day (SrR300); SrR 625mg/kg/day (SrR625); MV; SrR 625mg/kg/day plus MV (SrR625+MV). The vehicle and the SrR were administered by gavage 7 days/week and vibration (0.6g/60Hz) was performed for 20min/day, 5days/week. Bone mineral density (BMD) and body composition were evaluated by densitometry. Changes in cartilage were assessed 90 days after treatment by histomorphometry; immunohistochemistry analysis evaluating cell death (caspase-3), tumor necrosis factor-α (TNF-α), metalloproteinase 9 (MMP-9) and type II collagen; Osteoarthritis Research Society International (OARSI) grading system and glycosaminoglycans (GAGs) analyses. SrR-treated groups exhibited a lower OARSI grade, a smaller number of chondrocyte clusters, increased levels of chondroitin sulfate (CS) and decreased expression of caspase-3. Additionally, compared to all the groups, SrR300 exhibited increased levels of hyaluronic acid (HA). Vibration applied alone or in combination accelerated cartilage degradation, as demonstrated by increased OARSI grade, reduced number of chondrocytes, increased number of clusters, elevated expression of type II collagen and cell death, and was accompanied by decreased amounts of CS and HA; however, MV alone was able to reduce MMP-9. SrR and vibration modulate distinct responses in cartilage. Combined treatment accelerates degeneration. In contrast, SrR treatment at 300mg/kg/day attenuates osteoarthritis (OA) progression, improving cartilage matrix quality and preserving cell viability in ovariectomized rats.

Meniscal Surgery: Risk of Radiographic Joint Space Narrowing Progression and Subsequent Knee Replacement-Data from the Osteoarthritis Initiative.

Purpose To investigate the risk of radiographic joint space narrowing (JSN) progression evaluated in subjects with and those without underlying osteoarthritis at baseline and knee replacement (KR) associated with meniscal surgery in subjects with and those without a reported history of preceding knee trauma. Materials and Methods The HIPAA-compliant protocol was approved by the institutional review boards of the participating centers. Written informed consent was obtained from all participants. Subjects who underwent meniscal surgery with a preceding knee trauma at baseline (n = 564) and those without (n = 147) were drawn from the Osteoarthritis Initiative cohort (n = 4796). Radiographic JSN progression was evaluated by using Osteoarthritis Research Society International grading (progression in 1st-, 2nd-, 3rd-, 4th-, 6th-, or 8th-year radiographic findings compared with baseline). KR was assessed up to the 9th year of study (days passed from inclusion to KR or last follow-up). Cox hazard analysis was used to extract the adjusted hazard ratios (HRs) with adjustments for baseline age, sex, body mass index, physical activity, symptoms, and radiographic osteoarthritis features (Kellgren and Lawrence [KL] grade). Results Meniscal surgery with a history of preceding knee trauma was not associated with radiographic progression of JSN (adjusted HR, 0.91 [95% confidence interval {CI}: 0.78, 1.07]) or KR (adjusted HR, 1.02 [95% CI: 0.79, 1.34]; P = .854). However, meniscal surgery without a history of preceding knee trauma was associated with radiographic progression of JSN (adjusted HR, 1.27 [95% CI: 1.00, 1.63]) and KR (adjusted HR, 2.09 [95% CI: 1.52, 2.89]; P < .001). Additionally, there was a higher risk of KR in subjects with radiographic KL grade of less than 2 (adjusted HR, 6.97 [95% CI: 3.56, 13.64]; P < .001) at baseline in comparison with KL grade of at least 2 (adjusted HR, 1.76 [95% CI: 1.22, 2.54]; P < .05). Conclusion In contrast to subjects without a reported preceding trauma, meniscal surgery is not independently associated with increased risk of radiographic JSN progression and KR in patients with a reported preceding trauma. © RSNA, 2016 Online supplemental material is available for this article.

Nociceptive phenotype alterations of dorsal root ganglia neurons innervating the subchondral bone in osteoarthritic rat knee joints

Subchondral bone plays a role in generating knee joint pain in osteoarthritis (OA). The objective of this study was to clarify nociceptive phenotype alterations of subchondral bone afferents of the distal femur in mono-iodoacetate (MIA)-induced OA rats. OA was induced by intra-articular injection of MIA in rats. Two different retrograde tracers were separately injected into the knee joint cavity and the subchondral bone to identify joint and subchondral bone afferents. Immunohistochemistry was used at 2 weeks (early stage) and 6 weeks (advanced stage) after MIA injection to determine the expression of nociceptive markers (calcitonin gene-related peptide (CGRP) and tyrosine receptor kinase A (TrkA)) and the soma size distribution of CGRP-immunoreactive (IR) neurons. Histological subchondral bone and cartilage damage was scored according to the Osteoarthritis Research Society International grading system. Pain-related behavior was evaluated using weight distribution and mechanical sensitivity of the hind paw. OA caused an up-regulation of CGRP, TrkA and enlargement of soma size of CGRP-IR neurons in both joint and subchondral bone afferents. CGRP and TrkA expression in subchondral bone afferents gradually increased over 6 weeks. Furthermore, up-regulation of CGRP and TrkA in subchondral bone afferents displayed a strong correlation with the subchondral bone damage score. Up-regulation of nociceptive markers in subchondral bone afferents correlated with subchondral bone damage, suggesting that subchondral bone is a therapeutic target, especially in the case of advanced stage knee OA. In particular, CGRP and TrkA are potentially molecular therapeutic targets to treat joint pain associated with subchondral lesions.

No Association between Daily Walking and Knee Structural Changes in People at Risk of or with Mild Knee Osteoarthritis. Prospective Data from the Multicenter Osteoarthritis Study.

We investigated the association between objectively measured daily walking and knee structural change, defined either as radiographic worsening or as cartilage loss, in people at risk of or with knee osteoarthritis (OA). Participants from the Multicenter Osteoarthritis Study (MOST) with Kellgren-Lawrence grades 0-2 and daily walking (measured with the StepWatch) at the 60-month visit were included. Participants had fixed-flexion, weight-bearing radiographs and knee magnetic resonance images (MRI) at 60 and 84 months. Radiographic worsening was read in both knees using the Osteoarthritis Research Society International grading, and MRI were read for 1 knee using the Whole-Organ MRI Score semiquantitative scoring. OR and 95% CI were calculated comparing those in the middle tertile against the lowest and highest tertiles of daily walking using logistic regression models and generalized estimating equations. Data on walking with moderate to vigorous intensity (min with > 100 steps/min/day) were associated to structural change using multivariate and logistic regression models. The 1179 study participants (59% women) were 67.0 years old (± 7.6), with a mean (± SD) body mass index of 29.8 kg/m(2) (± 5.3) who walked 6981 (± 2630) steps/day. After adjusting for confounders, we found no significant associations between daily walking and radiographic worsening or cartilage loss. More time spent walking at a moderate to vigorous intensity was not associated with either radiographic worsening or cartilage loss. Results from the MOST study indicated no association between daily walking and structural changes over 2 years in the knees of people at risk of or with mild knee OA.

Insertional Achilles tendinopathy is associated with arthritic changes of the posterior calcaneal cartilage: a retrospective study.

BackgroundTo characterize the histological changes within the posterior calcaneal cartilage in patients with insertional Achilles tendinopathy (IAT) and test the relationships between severity of the histological changes and level of functional impairment.MethodsSixteen posterior calcaneal wall specimens of patients with IAT who had posterior calcaneal ostectomy were investigated. Hematoxylin-eosin stain, Toluidine-blue stain, Polarized light microscopy, and Masson Trichrome stain were used to characterize histological changes. Changes within the posterior calcaneal wall cartilage were graded according to Osteoarthritis Research Society International (OARSI) criteria. Functional scores were completed at the time of surgery according to the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score.ResultsMean age of patients was 48.9 years. Histological findings within the posterior calcaneal wall cartilage specimens were consistent with arthritic changes. OARSI grading indicated Grade 2 changes in one specimen, mean AOFAS score 60; Grade 3 changes in three specimens, AOFAS score 73.7 ± 2.5; Grade 4 changes in four specimens, AOFAS score 44 ± 21.4; Grade 5 changes in eight specimens, AOFAS score 48 ± 9.9. Higher OARSI grades were correlated with lower AOFAS scores (rho = −0.65, p < 0.01).ConclusionsDegenerative arthritic changes of the posterior calcaneal wall cartilage characterize patients with IAT and the severity of such changes is directly correlated to the degree of functional impairment.

Osteoarthritic cartilage lesions in the bovine patellar groove: A macroscopic, histological and immunohistological analysis

A high percentage of osteoarthritis (OA)-like patellar groove lesions in the stifle joint in calcium-deficient bulls has been recently reported. The prevalence of these lesions in bulls deficient in or supplemented with calcium was compared to findings in culled and healthy bulls to determine whether they represent normal anatomical variations, developmental anomalies or OA. It was hypothesized that the patellar groove lesions may represent OA. Distal cartilage samples from 160 femurs were analysed using a macroscopic Société Française d’Arthroscopie (SFA) OA grading system. Samples representing different SFA grades were subjected to Osteoarthritis Research Society International (OARSI) histological and high-mobility group box 1 (HMGB1) immunohistological OA grading. For a qualitative analysis three OA samples were immunostained for interleukin (IL)-1β, matrix metalloproteinase (MMP)-13 and collagenase-produced COL2-3/4M neoepitopes.Patellar groove lesions were found in 48% of the femurs and were highest in calcium-deficient animals (71%, P<0.001). All three different grading systems disclosed OA in culled bulls, but no focal areas of cartilage necrosis. OARSI and HMGB1 grades were fairly concordant (Spearman’s ρ=0.95, P<0.001; Cohen’s κ=0.23, P<0.005), both with a slight disparity with the SFA grade (ρ=0.80 and 0.87, P<0.01; κ=0.36 and 0.46, P<0.001). IL-1β, MMP-13 and COL2-3/4M staining patterns were compatible with OA. The study showed that patellar groove lesions are common in bulls. In all SFA, OARSI and HMGB1 graded samples the lesions clearly demonstrated OA and showed OA-typical pathophysiology. Arthroscopic SFA grading showed similar changes in calcium-deficient and calcium-supplemented bulls, but in the absence of a time course study and histological data the primary nature of these lesions could not be established with certainty.

Diffusion-Tensor Imaging of Human Articular Cartilage Specimens with Early Signs of Cartilage Damage

To assess the use of diffusion-tensor (DT) imaging of articular cartilage to detect and grade early cartilage damage in human specimens with early signs of cartilage damage. This study was approved by the institutional review board. Forty-three cartilage-on-bone samples drilled from 21 human patellae were examined with 17.6-T magnetic resonance (MR) imaging and a diffusion-weighted spin-echo sequence (spatial resolution, 50 × 100 × 800 μm). Subsequently, samples underwent histologic analysis with safranin O staining. Cartilage damage on safranin O histologic slides was quantified with Osteoarthritis Research Society International (OARSI) grades; grades ranged from 0 (healthy) to 6 (bone remodeling). Maps of longitudinal diffusivity (λ(l)), transverse diffusivity (λ(t)), mean diffusivity (MD), and fractional anisotropy (FA) were calculated. Cartilage was segmented, and region of interest (ROI) analysis was performed and compared with histologic findings. Significant differences in MR parameters between the OARSI groups were assessed with the Tukey test. The value of DT imaging in the diagnosis and grading of cartilage damage was assessed with logistic regression analysis. Samples had OARSI grades of 0 (n = 14), 1 (n = 11), 2 (n = 12), 3 (n = 4), and 4 (n = 2). Samples with an OARSI grade greater than 0 had significantly increased λ(l), λ(t), and MD (7%-25% increase) in the superficial cartilage growing deeper into cartilage with increasing OARSI grade. Samples with an OARSI grade greater than 0 showed significantly decreased FA in the deep cartilage (-25% to -35% decrease), suggesting that changes in the collagen architecture may occur early in cartilage degradation. DTI showed excellent performance in the detection of cartilage damage (accuracy, 0.95; 41 of 43 samples) and good performance in the grading of cartilage damage (accuracy, 0.74; 32 of 43 samples). DT imaging of articular cartilage can enable physicians to detect and grade early cartilage damage.

Different thresholds for detecting osteophytes and joint space narrowing exist between the site investigators and the centralized reader in a multicenter knee osteoarthritis study—data from the Osteoarthritis Initiative

To evaluate how the reading of knee radiographs by site investigators differs from that by an expert musculoskeletal radiologist who trained and validated them in a multicenter knee osteoarthritis (OA) study. A subset of participants from the Osteoarthritis Initiative progression cohort was studied. Osteophytes and joint space narrowing (JSN) were evaluated using Kellgren-Lawrence (KL) and Osteoarthritis Research Society International (OARSI) grading. Radiographs were read by site investigators, who received training and validation of their competence by an expert musculoskeletal radiologist. Radiographs were re-read by this radiologist, who acted as a central reader. For KL and OARSI grading of osteophytes, discrepancies between two readings were adjudicated by another expert reader. Radiographs from 96 subjects (49 women) and 192 knees (138 KL grade ≥ 2) were included. The site reading showed moderate agreement for KL grading overall (kappa = 0.52) and for KL ≥ 2 (i.e., radiographic diagnosis of "definite OA"; kappa = 0.41). For OARSI grading, the site reading showed substantial agreement for lateral and medial JSN (kappa = 0.65 and 0.71), but only fair agreement for osteophytes (kappa = 0.37). For KL grading, the adjudicator's reading showed substantial agreement with the centralized reading (kappa = 0.62), but only slight agreement with the site reading (kappa = 0.10). Site investigators over-graded osteophytes compared to the central reader and the adjudicator. Different thresholds for scoring of JSN exist even between experts. Our results suggest that research studies using radiographic grading of OA should use a centralized reader for all grading.