OARSI Grade Research Articles

Pattern of Inflammatory Molecules in Cartilage of the Impingement Zone in FAI Hips Suggests Origin of Hip Degeneration

Objectives: Femoroacetabular impingement (FAI) is considered a common cause of articular cartilage damage and early hip osteoarthritis (OA) in the young-adult patients. Molecular inflammation is believed to be one of the main initiators of hip OA. Matrix metalloproteinase (MMP)-13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 are known to function as extracellular matrix degrading enzymes in OA joints and have been shown to increase during the process of OA onset. Interleukin (IL)-1β is considered one of the key cytokines involved in the pathogenesis of OA. The aim of this study is to characterize inflammation and early OA pathways in cartilage from the head-neck impingement area in patients with symptomatic FAI cam. Methods: Cartilage samples were obtained in the head neck-junction area from 37 patients undergoing hip surgery between May 2017 and July 2018. Nine patients had a clinical diagnosis of FAI cam (FAI cam) and 15 patients presented advanced OA secondary to FAI cam (OA FAI). These cartilage samples were compared to cartilage samples obtained from similar head neck-junction area from 13 patients with advanced OA secondary to developmental dysplasia of the hip with no impingement (OA DDH). Radiographically, the α-angle was utilized to confirm hip impingement. All histological sections were stained with Safranin-O to assess cartilage degeneration. OARSI grade and Mankin score were used to quantify degenerative OA changes. Immunohistochemistry was performed for IL-1β, MMP-13 and ADAMTS-4. Quantification of immunopositive cells was performed in a blinded fashion. One-way analysis of variance with Tukey’s post hoc test was applied to analyze differences between three groups. Results: FAI cam patients were significantly younger than OA FAI patients (p<0.001) and OA DDH patients (p=0.0461) (Table 1). The average α-angle was significantly higher in the FAI cam and OA FAI groups than the OA DDH group (p<0.001). Cartilage samples from the FAI cam and the OA FAI groups showed degenerative changes. The average OARSI grade was significantly (p<0.01) higher in FAI cam (4.0±0.4) and OA FAI (3.6±0.9) compared to OA DDH (2.2±0.6). The average Mankin score was significantly (p<0.001) higher in FAI cam (7.6±1.2) and OA FAI (6.9±1.8) than OA DDH (4.1±0.7). IL-1β was expressed in cartilage samples from all groups, although the pattern varied.IL-1β was expressed mainly in the superficial layer in the OA DDH group but throughout all cartilage layers in the FAI cam and OA FAI groups. The % immunopositive cells were significantly (p<0.001) higher in FAI cam (58.1±8.9) and OA FAI (71.3±12.4) than OA DDH (28.9±6.3). Similar pattern of distribution was observed for MMP-13 (72.7±11.3, 70.2±18.2 vs 38.0±8.6; p<0.001, p<0.001) and ADAMTS-4 (73.1±7.3, 82.0±12.3 vs 45.3±12.7; p<0.001, p<0.001) (Figure 1). Conclusion: Osteoarthritic changes are evident in the cartilage from the head-neck area of patients with FAI cam morphology. Inflammatory molecules were evident in both early and late stages of hip impingement, suggesting the head-neck impingement area is a potential mediator of inflammation and joint degeneration. [Figure: see text][Table: see text]

Elastic, Viscoelastic and Fibril-Reinforced Poroelastic Material Properties of Healthy and Osteoarthritic Human Tibial Cartilage

Articular cartilage constituents (collagen, proteoglycans, fluid) are significantly altered during osteoarthritis (OA). A fibril-reinforced poroelastic (FRPE) material model can separate the contribution of each constituent on the mechanical response of cartilage. Yet, these properties and their OA related alterations are not known for human tibial cartilage. To answer this gap in the knowledge, we characterized the FRPE as well as elastic and viscoelastic properties of healthy and osteoarthritic human tibial cartilage. Tibial osteochondral explants (n = 27) harvested from 7 cadavers were mechanically tested in indentation followed by a quantification of elastic, viscoelastic and FRPE properties. Then they were histopathologically OARSI graded for the severity of OA. FRPE modeling revealed that non-fibrillar matrix modulus was higher in the healthy group compared to the early OA (p = 0.003) and advanced OA (p < 0.001) groups. The initial fibril network modulus was also higher in the healthy group compared to the early OA (p = 0.009) and advanced OA (p < 0.001) groups. The permeability correlated with the OARSI grade (p = 0.002, r = 0.56). For the first time, the FRPE properties were characterized for human tibial cartilage. This knowledge is crucial to improve the accuracy of computational knee joint models.

The evolving large-strain shear responses of progressively osteoarthritic human cartilage

The composition and structure of articular cartilage evolves during the development and progression of osteoarthritis (OA) resulting in changing mechanical responses. We aimed to assess the evolution of the intrinsic, large-strain mechanics of human articular cartilage-governed by collagen and proteoglycan and their interactions-during the progression of OA. We completed quasi-static, large-strain shear tests on 64 specimens from ten donors undergoing total knee arthroplasty (TKA), and quantified the corresponding state of OA (OARSI grade), structural integrity (PLM score), and composition (glycosaminoglycan and collagen content). We observed nonlinear stress-strain relationships with distinct hystereses for all magnitudes of applied strain where stiffnesses, nonlinearities, and hystereses all reduced as OA advanced. We found a reduction in energy dissipation density up to 80% in severely degenerated (OARSI grade 4, OA-4) vs normal (OA-1) cartilage, and more importantly, we found that even cartilage with a normal appearance in structure and composition (OA-1) dissipated 50% less energy than healthy (control) load-bearing cartilage (HL0). Changes in stresses and stiffnesses were in general less pronounced and did not allow us to distinguish between healthy load-bearing controls and very early-stage OA (OA-1), or to distinguish consistently among different levels of degeneration, i.e., OARSI grades. Our results suggest that reductions in energy dissipation density can be detected by bulk-tissue testing, and that these reductions precede visible signs of degeneration. We highlight the potential of energy dissipation, as opposed to stress- or stiffness-based measures, as a marker to diagnose early-stage OA.

Role of full-thickness cartilage defects in knee osteoarthritis (OA) incidence and progression: Data from the OA Initiative.

The purpose of this study is to determine whether full-thickness tibiofemoral cartilage defects are predictive of incident radiographic OA, progression of radiographic OA, and progression to severe radiographic OA. Participants in the OA Initiative (n = 1317, 38.1% male, mean age 60.9 years SD 9.2) with baseline MRIs and Kellgren-Lawrence (KL) OA grade 0-3 (none to moderate OA) were included. All participants had follow-up radiographs at mean 4.9 years (max 8.0). The effect of full-thickness defect presence, size, and location on risk of incident OA (KL grade 2+), overall progression of OA (increase in KL grade 1+ points), or compartment-specific OA progression was assessed with Cox proportional hazards modeling with adjustment for demographic factors, weight, and knee alignment. The yearly incidence of tibiofemoral OA was 0.3% (CI 0.2-0.4%); defect presence, size, and location were not associated with incident OA risk. The yearly rate of OA progression was 3.8% in participants without tibiofemoral full-thickness defects, 6.7% with medial defects, and 6.3% with lateral defects. Medial bipolar (kissing) lesions were an independent risk factor for OA progression as well as medial compartment progression. Lateral tibial-sided full-thickness defects increased risk of lateral progression (increase in lateral OARSI grade). In older adults, isolated full-thickness cartilage defects do not increase short-term risk of incident OA. However, in the setting of preexisting mild or moderate OA, medial bipolar (kissing) defects increase risk of overall OA progression (KL grade) as well as progression of medial compartment OA. Lateral tibial defects increase risk of lateral compartment OA progression. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Interleukin-10 and collagen type II immunoexpression are modulated by photobiomodulation associated to aerobic and aquatic exercises in an experimental model of osteoarthritis.

The aim of this study was to compare the effects of photobiomodulation (PBM) associated with an aerobic and an aquatic exercise training on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Fifty male Wistar rats were randomly divided into 5 groups: OA control group (CG), OA plus aerobic training group (AET), OA plus aquatic training group (AQT), OA plus aerobic training associated with PBM group (AETL), OA plus aquatic training associated with PBM group (AQTL). The aerobic training (treadmill; 16m/min; 50min/day) and the aquatic training (water jumping; 50-80% of their body mass) started 4weeks after the surgery and they were performed 3days/week for 8weeks. Moreover, PBM was performed after the physical exercise trainings on the left joint. Morphological characteristics and immunoexpression of IL-10, TGF-β, and collagen type I (Col I) and II (Col II) of the articular cartilage were evaluated. The results showed that all the treated groups (exercise and PBM) presented less intense signs of degradation (measured by histopathological analysis and OARSI grade system). Additionally, aerobic and aquatic exercise training rats (associated or not with PBM) showed increased IL-10 (AET p = 0.0452; AETL p = 0.03; AQTL p = 0.0193) and Col II (AET p = 0.012; AQT p = 0.0437; AETL p = 0.0001; AQTL p = 0.0001) protein expression compared to CG. Furthermore, a statistically higher TGF-β expression was observed in AET (p = 0.0084) and AETL (p = 0.0076) compared to CG. These results suggest that PBM associated with aerobic and aquatic exercise training were effective in mediating chondroprotective effects and maintaining the integrity of the articular tissue in the knees of OA rats.

In vitro method for 3D morphometry of human articular cartilage chondrons based on micro-computed tomography

SummaryObjectiveThe aims of this study were: to 1) develop a novel sample processing protocol to visualize human articular cartilage (AC) chondrons using micro-computed tomography (μCT), 2) develop and validate an algorithm to quantify the chondron morphology in 3D, and 3) compare the differences in chondron morphology between intact and osteoarthritic AC.MethodThe developed protocol is based on the dehydration of samples with hexamethyldisilazane (HMDS), followed by imaging with a desktop μCT. Chondron density and depth, as well as volume and sphericity, were calculated in 3D with a custom-made and validated algorithm employing semi-automatic chondron selection and segmentation. The quantitative parameters were analyzed at three AC depth zones (zone 1: 0–10%; zone 2: 10–40%; zone 3: 40–100%) and grouped by the OARSI histological grades (OARSI grades 0–1.0, n = 6; OARSI grades 3.0–3.5, n = 6).ResultsAfter semi-automatic chondron selection and segmentation, 1510 chondrons were approved for 3D morphometric analyses. The chondrons especially in the deeper tissue (zones 2 and 3) were significantly larger (P < 0.001) and less spherical (P < 0.001), respectively, in the OARSI grade 3–3.5 group compared to the OARSI grade 0–1.0 group. No statistically significant difference in chondron density between the OARSI grade groups was observed at different depths.ConclusionWe have developed a novel sample processing protocol for chondron imaging in 3D, as well as a high-throughput algorithm to semi-automatically quantify chondron/chondrocyte 3D morphology in AC. Our results also suggest that 3D chondron morphology is affected by the progression of osteoarthritis (OA).

Chondroitin sulfate and glucosamine sulfate associated to photobiomodulation prevents degenerative morphological changes in an experimental model of osteoarthritis in rats.

The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM treatments (GS/Gl + PBM). The CS/Gl started 48h after the surgery, and they were performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl administration on the left joint. Morphological characteristics and immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1β) and collagen type II (Col II) of the articular cartilage were evaluated. The results showed that all treated groups (CS/Gl and PBM) presented attenuation signs of degenerative process (measured by histopathological analysis) and lower density chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)]. Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM decreased IL-1β protein expression (p = 0.0359) and increased IL-10 (p = 0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed that CS/Gl associated with PBM was effective in modulating inflammatory process and preventing the articular tissue degradation in the knees OA rats.

Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation?

BackgroundTreatment of meniscus tears within the avascular region represents a significant challenge, particularly in a situation of early osteoarthritis. Cell-based tissue engineering approaches have shown promising results. However, studies have not found a consensus on the appropriate autologous cell source in a clinical situation, specifically in a challenging degenerative environment. The present study sought to evaluate the appropriate cell source for autologous meniscal repair in a demanding setting of early osteoarthritis.MethodsA rabbit model was used to test autologous meniscal repair. Bone marrow and medial menisci were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen-hyaluronan scaffolds before implantation. A punch defect model was performed on the lateral meniscus and then a cell-seeded scaffold was press-fit into the defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were assessed, and menisci were harvested for macroscopic, histological, and immunohistochemical evaluation using a validated meniscus scoring system. In conjunction, human meniscal cells isolated from non-repairable bucket handle tears and human MSCs were expanded and, using the pellet culture model, assessed for their meniscus-like potential in a translational setting through collagen type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay (ELISA), and gene expression analysis.ResultsAfter resections of the medial menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1). However, successful repair of meniscus punch defects was performed using either meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity for meniscal cell treatment. Furthermore, human MSCs had significantly increased collagen type II gene expression and production compared to meniscal cells (p < 0.05).ConclusionsThe regenerative potential of the meniscus by an autologous cell-based tissue engineering approach was shown even in a challenging setting of early osteoarthritis. Autologous MSCs and meniscal cells were found to have improved meniscal healing in an animal model, thus demonstrating their feasibility in a clinical setting. However, donor site morbidity, reduced availability, and reduced chondrogenic differentiation of human meniscal cells from debris of meniscal tears favors autologous MSCs for clinical use for cell-based meniscus regeneration.

Varus knee osteoarthritis: Elevated synovial CD15 counts correlate with inferior biomechanical properties of lateral-compartment cartilage.

The study analyzed the influence of synovitis on the histological and biomechanical properties of lateral-compartment cartilage. In a prospective cohort study, 84 patients (100 knees) with varus deformity of the knee were included. Osteochondral samples from the distal lateral femur underwent biomechanical and histologic analysis. Synovial tissue was sampled for histological (chronic synovitis score) and immunohistochemical evaluation of the degree of synovitis. CD15 (neutrophils), Ki-67 (dividing cells), and CD68 (macrophages) were tested in all synovial samples. While the histological synovitis score did not correlate with the degree of cartilage degeneration (histological OARSI grades), both CD15 (rs = 0.297, p = 0.006) and Ki-67 (rs = 0.249, p = 0.023) correlated with histological OARSI grades. There was a weak negative correlation of CD15 with biomechanical properties of cartilage of the distal lateral femur (aggregate modulus (Ha): rs = -0.125; p = 0.257; dynamic modulus (DM): rs = -0.216; p = 0.048). No correlations were observed for Ki-67 and CD68. In addition, biomechanical properties were inferior in knees with a CD15 of >8/high power field compared to knees with a CD15 of ≤8/high power field (Ha: p = 0.031, d = 0.46; DM: p = 0.005, d = 0.68). The study demonstrates an association of increased inflammatory activity with advanced cartilage degeneration. Lateral-compartment cartilage in knees with elevated synovial CD15 counts has a reduced ability to withstand compressive loads. CD15 might serve as an indicator for inferior biomechanical cartilage properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:841-846, 2018.

Cartilage And Subchondral Bone Histomorphometry In Osteoarthritis Knee.

Importance of subchondral bone in the pathogenesis and management of osteoarthritis retain recently the interest of both clinicians and researchers community. In fact, the integrity of articular cartilage relies on subchondral bone to provide mechanical support and nutrition supply. Herein, we investigated the relation between bone and cartilage structures and the vascular supply in human knee OA. METHODS: 37 osteoarthritic tibial plateaux were collected after a total knee replacement surgery. Samples from macroscopically different ICRS grades were prepared from tibial plateaux. Sample were scanned using the micro-computed tomography at 10μm resolution (Skyscan 1072, Bruker), projections were reconstructed using the manufacturer software. A manual segmentation has been performed on each sample to separate subchondral from trabecular bone and microarchitectural analysis was performed. The same samples were processed for histology, decalcified in 14% EDTA, sectioned into 4μm slides, coloured with HES and scored into 6 groups, based on histological OARSI score. Subchondral bone surface and thickness and articular cartilage surface were calculated. The number of vessels in the subchondral bone area were visually counted by two different operators and a VEGF immunofluorescent staining was performed. RESULTS: bone volume fraction, trabecular thickness, spacing, and number were positvely correlated OARSI grades. Also, blood vessels significantly increased from grade 1 to 5 (p<0.05). Yet, in grade 6 they significanly decreased (p<0.05). Yet, they were significantly less vessels in grade 6 compared to grade 5. CONCLUSION: Taken together, our data indicate an interplay and dynamic load-bearing structures between subchondral bone and cartilage. Understanding the signaling pathways, the cartilage-bone biochemical unit in joints and the intercellular communication between cartilage and subchondral bone may lead to development of more effective strategies for treating OA patients.

Obesity and radiological severity are associated with viscosupplementation failure in patients with knee osteoarthritis.

Viscosupplementation (VS) is still controversial. One of the key points is the lack of well-identified factors of response. We aimed to identify clinical and radiological factors associated with lack of relevant response after intra-articular (IA) hyaluronic acid (HA) injections in symptomatic knee osteoarthritis patients. A post hoc analysis of the HAV-2012 trial, a controlled, multicentre, double-blind, randomized, non-inferiority trial comparing 3 weekly IA injections of HA (HAnox-M or BioHA) for symptomatic tibiofemoral OA was performed. At inclusion, demographic, anthropometric, clinical data (WOMAC score, patient global assessment, presence of knee effusion), and radiological data (OARSI grade, patello-femoral involvement) were recorded. VS response was defined according to OMERACT-OARSI response criteria at month 6. Predictors of response were investigated in univariate then in multivariate analysis. One hundred and sixty-six patients with full available data were included. As baseline characteristics and treatment effectiveness were similar between the 2 HA groups, their data were pooled. The mean age was 65.2 [63.7-66.8] years; 101 (60.8%) were women; 73 (44.0%) had severe TF space narrowing. At 6 months, 113 patients (68.1%) were responders. Multivariate analysis showed that obesity (BMI ≥30 kg/m2) and radiological severity (OARSI grade 3) were significantly associated with VS failure (p = 0.001 and p = 0.008, respectively). Moreover, the association of obesity and severe TF space narrowing significantly increased the risk of VS failure. Baseline pain intensity and functional impairment were not associated with VS response. Consequently, IA injection of HA for knee OA should mainly be considered in subjects with low BMI and mild TF space narrowing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2269-2274, 2017.

Imaging of Osteoarthritic Human Articular Cartilage using Fourier Transform Infrared Microspectroscopy Combined with Multivariate and Univariate Analysis.

The changes in chemical composition of human articular cartilage (AC) caused by osteoarthritis (OA) were investigated using Fourier transform infrared microspectroscopy (FTIR-MS). We demonstrate the sensitivity of FTIR-MS for monitoring compositional changes that occur with OA progression. Twenty-eight AC samples from tibial plateaus were imaged with FTIR-MS. Hyperspectral images of all samples were combined for K-means clustering. Partial least squares regression (PLSR) analysis was used to compare the spectra with the OARSI grade (histopathological grading of OA). Furthermore, the amide I and the carbohydrate regions were used to estimate collagen and proteoglycan contents, respectively. Spectral peak at 1338 cm−1 was used to estimate the integrity of the collagen network. The layered structure of AC was revealed using the carbohydrate region for clustering. Statistically significant correlation was observed between the OARSI grade and the collagen integrity in the superficial (r = −0.55) and the deep (r = −0.41) zones. Furthermore, PLSR models predicted the OARSI grade from the superficial (r = 0.94) and the deep (r = 0.77) regions of the AC with high accuracy. Obtained results suggest that quantitative and qualitative changes occur in the AC composition during OA progression, and these can be monitored by the use of FTIR-MS.

Safety and efficacy of intra-articular injections of a combination of hyaluronic acid and mannitol (HAnOX-M) in patients with symptomatic knee osteoarthritis: Results of a double-blind, controlled, multicenter, randomized trial

BackgroundTo compare both safety and efficacy of a novel intra-articular viscosupplement made of intermediate molecular weight (MW) hyaluronic acid (HA) mixed with high concentration of mannitol with a marketed high MW HA, in patients with knee osteoarthritis (OA). MethodsPatients with symptomatic knee OA, with radiological OARSI grades 1 to 3, were enrolled in a controlled, double-blind, parallel-group, non-inferiority trial. They were randomized to receive three intra-articular injections, at weekly intervals, of either HAnOX-M made of a combination of HA (MW one to 1.5MDa, 31mg/2ml) and mannitol (70mg/2ml) or Bio-HA (MW 2.3 to 3.6MDa, 20mg/2ml). The primary outcome was six-month change in the WOMAC pain subscale (0 to 20). Sample size was calculated according to a non-inferiority margin of 1.35. Secondary endpoints included six-month change in function and walking pain, analgesic consumption and safety. ResultsThe intention-to-treat (ITT) and per-protocol (PP) populations consisted of 205 and 171 patients. HAnOX-M and Bio-Ha groups did not differ statistically at baseline. The primary analysis was conducted in the PP population, then in the ITT population. The average WOMAC pain score at baseline was 9.5 in both groups. Mean (SD) variations in WOMAC pain score were −4.4 (3.8) and −4.5 (4.3) mm, for HAnOX and Bio-HA respectively, satisfying the claim for non-inferiority. Similar results were obtained for all other secondary endpoints. ConclusionTreatment with of HAnOX-M is effective to alleviate knee OA symptoms and to improve joint function over six months, with similar safety than conventional HA viscosupplement.

Association between subchondral bone structure and osteoarthritis histopathological grade.

ABSTRACTDespite increasing evidence that subchondral bone contributes to osteoarthritis (OA) pathogenesis, little is known about local changes in bone structure compared to cartilage degeneration. This study linked structural adaptation of subchondral bone with histological OA grade. Twenty‐five osteochondral samples of macroscopically different degeneration were prepared from tibiae of 14 patients. Samples were scanned with micro‐computed tomography (μCT) and both conventional structural parameters and novel 3D parameters based on local patterns were analyzed from the subchondral plate and trabecular bone. Subsequently, samples were processed for histology and evaluated for OARSI grade. Each bone parameter and OARSI grade was compared to assess structural adaptation of bone with OA severity. In addition, thicknesses of cartilage, calcified cartilage, and subchondral plate were analyzed from histological sections and compared with subchondral bone plate thickness from μCT. With increasing OARSI grade, the subchondral plate became thicker along with decreased specific bone surface, while there was no change in tissue mineral density. Histological analysis showed that subchondral plate thickness from μCT also includes calcified cartilage. Entropy of local patterns increased with OA severity, reflecting higher tissue heterogeneity. In the trabecular compartment, bone volume fraction and both trabecular thickness and number increased with OARSI grade while trabecular separation and structure model index decreased. Also, elevation of local patterns became longitudinal in the subchondral plate and axial transverse in trabecular bone with increasing OARSI grade. This study demonstrates the possibility of radiological assessment of OA severity by structural analysis of bone. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:785–792, 2017.

Quantitative study on morphology of calcified cartilage zone in OARSI 0∼4 cartilage from osteoarthritic knees

ObjectiveTo observe the morphological feature of calcified cartilage zone (CCZ) in mild to moderate degeneration of cartilages from patients with knee osteoarthritis (OA), revealing the pattern of CCZ during OA progression and its correlation to the surrounding structures. MethodsOsteochondral specimens were collected from the center of the lateral tibial plateau of 42 OA patients undergoing total knee replacement. Sections were stained with hematoxylin-eosin and Safranin-O/Fast green. Morphological parameters (thickness of CCZ, hyaline cartilage, and subchondral bone, roughness of tidemark and cement line, number of tidemarks and chondrocytes in CCZ, area and number of vascular channels in CCZ) of OARSI grades 0∼4 cartilages were measured. ResultsThe thickness of CCZ increased with grading except in grade 2. This changing trend of CCZ was in accordance with chondrocyte number and area of vascular channel. The roughness of cement lines increased with the grading, and was correlated with the thickness of subchondral bone. The roughness of tidemarks was associated with thickness of hyaline cartilage in grade 0 to grade 3. ConclusionsIn mild OA, the thickness of CCZ was increased at first and then decreased, the roughness of tidemark and cement line was nearly unchanged, which suggests that the pathological change of CCZ is reversible. However, in moderate OA, the thickness of CCZ, the roughness of tidemark and cement line were progressively increased, which suggests that the pathological change of CCZ is irreversible.

Early osteoarthritis of the knee.

There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50% of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.

Mechanical properties of normal and osteoarthritic human articular cartilage

Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the mechanical properties of normal and osteoarthritic human articular cartilage and enhances our ability to model this tissue using simple isotropic hyperelastic materials.

OARSI osteoarthritis cartilage histopathology assessment system: A biomechanical evaluation in the human knee.

The study compared the OARSI osteoarthritis cartilage histopathology assessment system with the biomechanical quality of human in vivo cartilage samples. In a prospective cohort study, 84 patients (100 knees) with varus deformity of the knee were included between May, 2010 and January, 2012. Osteochondral samples underwent biomechanical and histologic analysis. The dynamic modulus significantly (p < 0.001) decreased with each advancing grade of degeneration from OARSI Grade 0 (surface intact) to OARSI Grade 4 (erosion). For the aggregate modulus, there were significant (p < 0.001) differences between OARSI Grade 0 and OARSI Grade 1 as well as between OARSI Grade 1 and OARSI Grade 2. From OARSI Grade 2 to OARSI Grade 5, no differences in aggregate modulus occurred. The new OARSI grading system provides useful information about the functional properties of cartilage. There is a significant difference in cartilage stiffness between samples with intact surface and no signs of degeneration (OARSI Grade 0) and samples with intact surface and early signs of arthritis (OARSI Grade 1). Surgeons performing joint preserving procedures have to be aware that in knees with an intact cartilage surface (OARSI Grade 0/1), significant differences in the biomechanical properties may exist.

Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint

The pathogenesis of osteoarthritis (OA) is not fully understood, but bone changes are suggested to be important. Bone turnover and bone volume (BV) in human hip OA were investigated in relation to the overlying cartilage degeneration using design-based stereological estimators. Femoral heads were obtained from 25 end-stage OA patients and 24 controls (CTL). Design-based stereological methods were used for sampling and quantification to obtain absolute estimates of volume and surface in the central trabecular and the subarticular bone region. The subarticular bone was further subdivided into regions according to the OARSI-score of the overlying articular cartilage in which erosion and osteoid surfaces were estimated. In the subarticular region, bone volume (BV/TV) was 15.0% higher in OA patients compared to CTL; The fraction of erosive (ES/BS) and osteoid surfaces (OS/BS) were 56.2% and 72.8% higher in OA compared to CTL. In subarticular regions with none to mild cartilage degeneration (OARSI grade 0-2), ES/BS and OS/BS were 48.6% and 59.9% higher in OA compared to CTL, whereas BV/TV did not differ between OA and CTL. In human end-stage hip OA, BV and bone turnover correlate with the degree of local cartilage degeneration. Subarticular bone sclerosis was only present in regions corresponding to end-stage OA. However, in regions with only none to mild cartilage degeneration the underlying bone had significantly higher turnover in OA patients compared to the control group, suggesting that high bone turnover may contribute to the early pathogenesis of OA.

Multiparametric MRI assessment of human articular cartilage degeneration: Correlation with quantitative histology and mechanical properties.

To evaluate the sensitivity of quantitative MRI techniques (T1 , T1,Gd , T2 , continous wave (CW) T1ρ dispersion, adiabatic T1ρ , adiabatic T2ρ , RAFF and inversion-prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration. Osteochondral samples (n = 14) were obtained from the tibial plateaus of patients undergoing total knee replacement. MRI of the specimens was performed at 9.4T and the relaxation time maps were evaluated in the cartilage zones. For reference, quantitative histology, OARSI grading and biomechanical measurements were performed and correlated with MRI findings. All MRI parameters, except T1,Gd , showed statistically significant differences in tangential and full-thickness regions of interest (ROIs) between early and advanced osteoarthritis (OA) groups, as classified by OARSI grading. CW-T1ρ showed significant dispersion in all ROIs and featured classical laminar structure of cartilage with spin-lock powers below 1000 Hz. Adiabatic T1ρ , T2ρ , CW-T1ρ, MT, and RAFF correlated strongly with OARSI grade and biomechanical parameters. MRI parameters were able to differentiate between early and advanced OA. Furthermore, rotating frame methods, namely adiabatic T1ρ , adiabatic T2ρ , CW-T1ρ , and RAFF, as well as MT experiment correlated strongly with biomechanical parameters and OARSI grade, suggesting high sensitivity of the parameters for cartilage degeneration. Magn Reson Med 74:249-259, 2015. © 2014 Wiley Periodicals, Inc.