Arthroscopic partial meniscectomy versus placebo surgery for a degenerative meniscus tear : a 2-year follow-up of the randomised controlled trial

Objective To assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus. Methods In this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35-65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out. Results In the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, -4.3; 95% CI, -11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (-3.2; -8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (-0.4; -1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups. Conclusions In this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.Peer reviewe

Synovial fluid fatty acid profiles are differently altered by inflammatory joint pathologies in the shoulder and knee joints

Abstract Anomalies of fatty acid (FA) metabolism characterize osteoarthritis (OA) and rheumatoid arthritis (RA) in the knee joint. No previous study has investigated the synovial fluid (SF) FA manifestations in these aging-related inflammatory diseases in the shoulder. The present experiment compared the FA alterations between the shoulder and knee joints in patients with end-stage OA or end-stage RA. SF samples were collected during glenohumeral or knee joint surgery from trauma controls and from OA and RA patients (n = 42). The FA composition of SF total lipids was analyzed by gas chromatography with flame ionization and mass spectrometric detection and compared across cohorts. The FA signatures of trauma controls were mostly uniform in both anatomical locations. RA shoulders were characterized by elevated percentages of 20:4n-6 and 22:6n-3 and with reduced proportions of 18:1n-9. The FA profiles of OA and RA knees were relatively uniform and displayed lower proportions of 18:2n-6, 22:6n-3 and total n-6 polyunsaturated FAs (PUFAs). The results indicate location- and disease-dependent differences in the SF FA composition. These alterations in FA profiles and their potential implications for the production of PUFA-derived lipid mediators may affect joint lubrication, synovial inflammation and pannus formation as well as cartilage and bone degradation and contribute to the pathogeneses of inflammatory joint diseases

Near-infrared spectroscopy for mapping of human meniscus biochemical constituents

Abstract Degenerative changes in meniscus are diagnosed during surgery by means of mechanical testing and visual evaluation. This method is qualitative and highly subjective, providing very little information on the internal state of the meniscus. Thus, there is need for novel quantitative methods that can support decision-making during arthroscopic surgery. In this study, we investigate the potential of near-infrared spectroscopy (NIRS) for mapping the biochemical constituents of human meniscus, including water, uronic acid, and hydroxyproline contents. Partial least squares regression models were developed using data from 115 measurement locations of menisci samples extracted from 7 cadavers and 11 surgery patient donors. Model performance was evaluated using an independent test set consisting of 55 measurement locations within a meniscus sample obtained from a separate cadaver. The correlation coefficient of calibration (ρtraining), test set (ρtest), and root-mean-squared error of test set (RMSEP) were as follows: water (ρtraining = 0.61, ρtest = 0.39, and RMSEP = 2.27 percentage points), uronic acid (ρtraining = 0.68, ρtest = 0.69, and RMSEP = 6.09 basis points), and hydroxyproline (ρtraining = 0.84, ρtest = 0.58, and error = 0.54 percentage points). In conclusion, the results suggest that NIRS could enable rapid arthroscopic mapping of changes in meniscus biochemical constituents, thus providing means for quantitative assessment of meniscus degeneration

Elastic, viscoelastic and fibril-reinforced poroelastic material properties of healthy and osteoarthritic human tibial cartilage

Abstract 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

Structure–function relationships of healthy and osteoarthritic human tibial cartilage:experimental and numerical investigation

Abstract Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (> 0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension

Raman microspectroscopic analysis of the tissue-specific composition of the human osteochondral junction in osteoarthritis:a pilot study

Abstract This study investigates the influence of osteoarthritis (OA) disease severity on the bio-composition of the osteochondral junction at the human tibial plateau using Raman microspectroscopy. We specifically aim to analyze the spatial composition of mineralized osteochondral tissues, i.e., calcified cartilage (CC) and subchondral bone plate (SBP) from unfixed, hydrated specimens. We hypothesize that the mineralization of CC and SBP decreases in advanced OA. Twenty-eight cylindrical osteochondral samples (d = 4 mm) from tibial plateaus of seven cadaveric donors were harvested and sorted into three groups following histopathological grading: healthy (n = 5), early OA (n = 8), and advanced OA (n = 15). Raman spectra were subjected to multivariate cluster analyses to identify different tissues. Finally, the tissue-specific composition was analyzed, and the impact of OA was statistically evaluated with linear mixed models. Cluster analyses of Raman spectra successfully distinguished CC and SBP as well as a tidemark region and uncalcified cartilage. CC was found to be more mineralized and the mineral was more crystalline compared with SBP. Both tissues exhibited similar compositional changes as a function of histopathological OA severity. In early OA, the mineralization tends to increase, and the mineral contains fewer carbonate substitutions. Compared with early OA, mineral crystals are rich in carbonate while the overall mineralization decreases in advanced OA. This Raman spectroscopic study advances the methodology for investigating the complex osteochondral junction from native tissue. The developed methodology can be used to elucidate detailed tissue-specific changes in the chemical composition with advancing OA

Characterization of hyaluronan-coated extracellular vesicles in synovial fluid of patients with osteoarthritis and rheumatoid arthritis

Abstract Background: Hyaluronic acid (HA) is the major extracellular matrix glycosaminoglycan with a reduced synovial fluid (SF) concentration in arthropathies. Cell-derived extracellular vesicles (EV) have also been proposed to contribute to pathogenesis in joint diseases. It has recently been shown that human SF contains HA-coated EV (HA–EV), but their concentration and function in joint pathologies remain unknown. Methods: The aim of the present study was to develop an applicable method based on confocal laser scanning microscopy (CLSM) and image analysis for the quantification of EV, HA-particles, and HA–EV in the SF of the human knee joint. Samples were collected during total knee replacement surgery from patients with end-stage rheumatoid arthritis (RA, n = 8) and osteoarthritis (OA, n = 8), or during diagnostic/therapeutic arthroscopy unrelated to OA/RA (control, n = 7). To characterize and quantify EV, HA-particles, and HA–EV, SF was double-stained with plasma membrane and HA probes and visualized by CLSM. Comparisons between the patient groups were performed with the Kruskal–Wallis analysis of variance. Results: The size distribution of EV and HA-particles was mostly similar in the study groups. Approximately 66% of EV fluorescence was co-localized with HA verifying that a significant proportion of EV carry HA. The study groups were clearly separated by the discriminant analysis based on the CLSM data. The intensities of EV and HA-particle fluorescences were lower in the RA than in the control and OA groups. Conclusions: CLSM analysis offers a useful tool to assess HA–EV in SF samples. The altered EV and HA intensities in the RA SF could have possible implications for diagnostics and therapy

Quantitative dual contrast CT technique for evaluation of articular cartilage properties

Impact injuries\ua0of cartilage may initiate post-traumatic degeneration, making early detection of injury imperative for timely surgical or pharmaceutical interventions. Cationic (positively-charged) CT contrast agents detect loss of cartilage proteoglycans (PGs) more sensitively than anionic (negatively-charged) or non-ionic (non-charged, i.e., electrically neutral) agents. However, degeneration related loss of PGs and increase in water content have opposite effects on the diffusion of the cationic agent, lowering its sensitivity. In contrast to cationic agents, diffusion of non-ionic agents is governed only by steric hindrance and water content\ua0of cartilage. We hypothesize that sensitivity of\ua0an iodine(I)-based cationic agent may be enhanced by simultaneous use of a non-ionic gadolinium(Gd)-based agent. We introduce a quantitative dual energy CT technique (QDECT) for simultaneous quantification of two contrast agents in cartilage. We employ this technique to improve the sensitivity of cationic CA4+ (q =+4) by normalizing its partition in cartilage with that of non-ionic gadoteridol. The technique was evaluated with measurements of contrast agent mixtures of known composition and human osteochondral samples (n = 57) after immersion (72\ua0h) in mixture of CA4+ and gadoteridol. Samples were arthroscopically graded and biomechanically tested prior to QDECT (50/100\ua0kV). QDECT determined contrast agent mixture compositions correlated with the true compositions (R = 0.99, average error = 2.27%). Normalizing CA4+ partition in cartilage with that of gadoteridol improved correlation with equilibrium modulus (from ρ = 0.701 to 0.795). To conclude, QDECT enables simultaneous quantification of I and Gd contrast agents improving diagnosis of cartilage integrity and biomechanical status

High-resolution infrared microspectroscopic characterization of cartilage cell microenvironment

Abstract The lateral resolution of infrared spectroscopy has been inadequate for accurate biochemical characterization of the cell microenvironment, a region regulating biochemical and biomechanical signals to cells. In this study, we demonstrate the capacity of a high-resolution Fourier transform infrared microspectroscopy (HR-FTIR-MS) to characterize the collagen content of this region. Specifically, we focus on the collagen content in the cartilage cell (chondrocyte) microenvironment of healthy and osteoarthritic (OA) cartilage. Human tibial cartilage samples (N = 28) were harvested from 7 cadaveric donors and graded for OA severity (healthy, early OA, advanced OA). HR-FTIR-MS was used to analyze the collagen content of the chondrocyte microenvironment of five distinct zones across the tissue depth. HR-FTIR-MS successfully showed collagen content distribution across chondrocytes and their environment. In zones 2 and 3 (10 - 50% of the tissue thickness), we observed that collagen content was smaller (P < 0.05) in early OA compared to the healthy tissue in the vicinity of cells (pericellular region). The collagen content loss was extended to the extracellular matrix in advanced OA tissue. No significant differences in the collagen content of the chondrocyte microenvironment were observed between the groups in the most superficial (0–10%) and deep zones (50–100%). HR-FTIR-MS revealed collagen loss in the early OA cartilage pericellular region before detectable changes in the extracellular matrix in advanced OA. HR-FTIR-MS-based compositional assessment enables a better understanding of OA-related changes in tissues. This technique can be used to identify new disease mechanisms enabling better intervention strategies

Quantifying Subresolution 3D Morphology of Bone with Clinical Computed Tomography

| openaire: EC/H2020/336267/EU//3D-OA-HISTOThe aim of this study was to quantify sub-resolution trabecular bone morphometrics, which are also related to osteoarthritis (OA), from clinical resolution cone beam computed tomography (CBCT). Samples (n = 53) were harvested from human tibiae (N = 4) and femora (N = 7). Grey-level co-occurrence matrix (GLCM) texture and histogram-based parameters were calculated from CBCT imaged trabecular bone data, and compared with the morphometric parameters quantified from micro-computed tomography. As a reference for OA severity, histological sections were subjected to OARSI histopathological grading. GLCM and histogram parameters were correlated to bone morphometrics and OARSI individually. Furthermore, a statistical model of combined GLCM/histogram parameters was generated to estimate the bone morphometrics. Several individual histogram and GLCM parameters had strong associations with various bone morphometrics (|r| > 0.7). The most prominent correlation was observed between the histogram mean and bone volume fraction (r = 0.907). The statistical model combining GLCM and histogram-parameters resulted in even better association with bone volume fraction determined from CBCT data (adjusted R-2 change = 0.047). Histopathology showed mainly moderate associations with bone morphometrics (|r| > 0.4). In conclusion, we demonstrated that GLCM- and histogram-based parameters from CBCT imaged trabecular bone (ex vivo) are associated with sub-resolution morphometrics. Our results suggest that sub-resolution morphometrics can be estimated from clinical CBCT images, associations becoming even stronger when combining histogram and GLCM-based parameters.Peer reviewe