Trapeziectomy and tendon suspension with or without a mitek anchor fixation in the thumb basal joint osteoarthritis.

Partial trapeziectomy with suspension ligamentoplasty is a commonly performed treatment of thumb osteoarthritis. Nevertheless, the post-operative recovery remains long and critical reason for which different modifications of the surgical technique have been proposed. To compare two suspension ligamentoplasty techniques, one with a mitek anchor and another without, a retrospective study of 55 consecutive operated patients was performed. A detailed clinical analysis of pain, function and a radiologic assessment of the trapeziometacarpal space were performed. Mitek anchor fixation was associated with a shorter convalescence period. However, in spite of an improved radiological maintenance of the scaphometacarpal space, mitek anchor fixation was associated with an impaired postoperative function and residual pain when compared with the conventional suspension ligamentoplasty procedure. Patient's satisfaction was comparable in both groups. In our series stabilization of the suspension ligamentoplasty procedure by the insertion of a mitek anchor did not bring the hoped benefits to the patients with a trapeziometacarpal arthritis.

Anatomical distribution of areas of preserved cartilage in advanced femorotibial osteoarthritis using CT arthrography (Part 1).

OBJECTIVE: To determine subregions of normal and abnormal cartilage in advanced stages of femorotibial osteoarthritis (OA) by mapping the entire femorotibial joint in a cohort of pre-total knee replacement (TKR) OA knees. DESIGN: We defined an areal subdivision of the femorotibial articular cartilage surface on CT arthrography (CTA), allowing the division of the femorotibial articular surface into multiple (up to n = 204 per knee) subregions and the comparison of the same areas between different knees. Two readers independently classified each cartilage area as normal, abnormal or non-assessable in 41 consecutive pre-TKR OA knees. RESULTS: A total of 6447 cartilage areas (from 41 knees) were considered assessable by both readers. The average proportion of preserved cartilage was lower in the medial femorotibial joint than in the lateral femorotibial joint for both readers (32.0/69.8% and 33.9/68.5% (medial/lateral) for reader 1 and 2 respectively, all P < 0.001). High frequencies of normal cartilage were observed at the posterior aspect of the medial condyle (up to 89%), and the anterior aspect of the lateral femorotibial compartment (up to 100%). The posterior aspect of the medial condyle was the area that most frequently exhibited preserved cartilage in the medial femorotibial joint, contrasting with the high frequency of cartilage lesions in the rest of that compartment. CONCLUSIONS: Cartilage at the posterior aspect of the medial condyle, and at the anterior aspect of the lateral femorotibial compartment, may be frequently preserved in advanced grades of OA.

Imagerie et arthrose [Imaging in osteoarthritis].

Plain radiography remains useful for the diagnosis of osteoarthritis, even if it is not always essential. It is moreover poorly correlated with symptoms, as it reflects rather the accumulation of damage then active processes. Similarly, it is a poor indicator of the progression of osteoarthritis. Modem imaging, particularly MRI, has allowed us to understand better the evolving processes, demonstrating a good correlation with symptoms and a better predictive value of clinical course. It has gradually replaced standard radiography in the study because it directly demonstrates sequelae and the active processes in all the structures of the joint. It remains clinically indicated only to exclude an alternative diagnosis or to determine a possible complication of osteoarthritis.

Outcome evaluation of ankle osteoarthritis treatments using spatio-temporal gait parameters and plantar pressure during unconstrained long distance walking : P25

Introduction: Ankle arthrodesis (AD) and total ankle replacement (TAR) are typical treatments for ankle osteoarthritis (AO). Despite clinical interest, there is a lack of their outcome evaluation using objective criteria. Gait analysis and plantar pressure assessment are appropriate to detect pathologies in orthopaedics but they are mostly used in lab with few gait cycles. In this study, we propose an ambulatory device based on inertial and plantar pressure sensors to compare the gait during long-distance trials between healthy subjects (H) and patients with AO or treated by AD and TAR. Methods: Our study included four groups: 11 patients with AO, 9 treated by TAR, 7 treated by AD and 6 control subjects. An ambulatory system (Physilog®, CH) was used for gait analysis; plantar pressure measurements were done using a portable insole (Pedar®-X, DE). The subjects were asked to walk 50 meters in two trials. Mean value and coefficient of variation of spatio-temporal gait parameters were calculated for each trial. Pressure distribution was analyzed in ten subregions of foot. All parameters were compared among the four groups using multi-level model-based statistical analysis. Results: Significant difference (p <0.05) with control was noticed for AO patients in maximum force in medial hindfoot and forefoot and in central forefoot. These differences were no longer significant in TAR and AD groups. Cadence and speed of all pathologic groups showed significant difference with control. Both treatments showed a significant improvement in double support and stance. TAR decreased variability in speed, stride length and knee ROM. Conclusions: In spite of a small sample size, this study showed that ankle function after AO treatments can be evaluated objectively based on plantar pressure and spatio-temporal gait parameters measured during unconstrained walking outside the lab. The combination of these two ambulatory techniques provides a promising way to evaluate foot function in clinics.

A systems view of risk factors for knee osteoarthritis reveals insights into the pathogenesis of the disease.

Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g., mechanical) becomes abnormal, and it is the interaction with the other components (e.g., biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a 5 year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.

Role of basic calcium phosphate crystals in osteoarthritis

L'arthrose est une maladie dégénérative des articulations due à une dégradation progressive du cartilage. La calcification de l'articulation (essentiellement due à des dépôts de cristaux de phosphate de calcium basique -cristaux BCP-) est une caractéristique de cette maladie. Cependant, le rôle des cristaux BCP reste à déterminer. Nous avons tout d'abord déterminé en utilisant des cultures primaires de chondrocytes que les cristaux de BCP induisaient la production de la cytokine IL-6, via une signalisation intracellulaire implicant les kinase Syk, PI3 et Jak et Stat3. Les cristaux de BCP induisent également la perte de protéoglycanes et l'expression de IL-6 dans des explants de cartlage humain et ces deux effets peuvent être bloqués par un inhibiteur de IL-6, le Tocilizumab. Par ailleurs, nous avons trouvé que l'IL-6 ajouté à des chondrocytes, favorisait la formation de cristax de BCP et augmentait l'expression de gènes impliqués dans le processus de minéralisation : Ank (codant pour un transporteur de pyrophooshate), Annexin5 (codant pour un canal calcique) et Pit-1 (codant pour un transporteur de phoshate). In vivo, les cristaux de BCP injectés dans l'articulation de souris induisent une érosion du cartilage. Dans un modèle murin d'arthrose du genou induit par ménisectomie, nous avons observé la formation progressive de cristaux de BCP. Fait intéressant, la présence de ces cristaux dans l'articulation précédait la destruction du cartilage. Un agent susceptible de bloquer les calcifications tel que le sodium thiosulfate (STS), administré à des souris ménisectomisées, inhibait le dépôt intra-articulaire de ces cristaux ainsi que l'érosion du cartilage. Nous avons identifié ainsi un cercle vicieux dans l'arthrose, les cristaux induisant l'interleukine-6 et l'interleukine-6 induisant la formation de ces cristaux. Nous avons étudié si on pouvait bloquer cette boucle cristaux de BCP-IL6 soit par des agents décalcifiants, soit par des inhibiteurs d'IL-6. In vitro, des anticorps anti IL- 6 ou des inhibiteurs de signalisation, inhibaient significativement IL-6 et la minéralisation induite par IL-6. De même le STS inhibait la formation de ces cristaux et la production de l'IL-6. Tout récemment, nous avons trouvé que des inhibiteurs de la xanthine oxidoréductase étaient aussi capables d'inhiber à la fois la production d'IL-6 et la minéralization des chondrocytes. Finalement, nous avons pu exclure un rôle du système IL-1 dans le modèle d'arthrose induite par ménisectomie, les souris déficientes pour IL-1a/ß, MyD88 et l'inflammasome NLRP3 n'étant pas protégées dans ce modèle d'arthrose. L'ensemble de nos résultats montre que les cristaux BCP sont pathogéniques dans l'arthrose et qu'un inhibiteur de minéralisation tel que le STS ou un inhibiteur de l'interleukine-6 constitueraient des nouvelles thérapies pour l'arthrose. -- Osteoarthritis (OA), the most common degenerative disorder of the joints, results from an imbalance between the breakdown and repair of the cartilage and surrounding articular structures. Joint calcification (essentially due to basic calcium phosphate (BCP) crystal deposition) is a characteristic feature of OA. However, the role of BCP crystal deposition in the pathogenesis of OA remains unclear[1][1]. We first demonstrated that in primary murine chondrocytes exogenous BCP crystals led to IL-6 up-modulation and that BCP crystal signaling pathways involved Syk and PI3 kinases, and also gp130 associated molecules, Jak2 and Stat3. BCP crystals also induced proteoglycan loss and IL-6 expression in human cartilage expiants, (which were significantly reduced by an IL-6 inhibitor). In addition, we found that in chondrocytes exogenous IL-6 promoted calcium-containing crystal formation and up- regulation of genes codifying for proteins involved in the calcification process: the inorganic pyrophosphate transport channel Ank, the calcium channel Annexinö and the sodium/phosphate cotransporter Piti. In vivo, BCP crystals injected into murine knee joints induced cartilage erosion. In the menisectomy model, increasing deposits, identified as BCP crystals, were progressively observed around the joint before cartilage erosion. These deposits strongly correlated with cartilage degradation and IL-6 expression. These results demonstrated that BCP crystals deposition and IL-6 production are mutually reinforcing in the osteoarthritic pathogenic process. We then investigated if we could block the BCP-IL6 loop by either targeting IL-6 production or BCP crystal deposits. Treatment of chondrocytes with anti-IL-6 antibodies or inhibitors of IL-6- signaling pathway significantly inhibited IL-6-induced crystal formation. Similarly, sodium thiosulfate (STS), a well-known systemic calcification inhibitor, decreased crystal deposition as well as HA-induced IL-6 secretion in chondrocytes and, in vivo, it decreased crystal deposits size and cartilage erosion in menisectomized knees. Interestingly, we also found that xanthine-oxidoreductase (XO) inhibitors inhibited both IL-6 production and calcium crystal depositis in chondrocytes. We began to unravel the mechanisms involved in this coordinate modulation of IL-6 and mineralization. STS inhibited Reactive Oxygen Species (ROS) generation and we are currently investigating whether XO represents a major source of ROS in chondrocyte mineralization. Finally, we ruled out that IL-1 activation/signaling plays a role in the murine model of OA induced by menisectomy, as IL-1a/ß, the IL-1 R associated molecule MyD88 and NLRP3 inflammasome deficient mice were not protected in this model of OA. Moreover TLR-1, -2, -4,-6 deficient mice had a phenotype similar to that of wild-type mice. Altogether our results demonstrated a self-amplification loop between BCP crystals deposition and IL-6 production, which represents an aggravating process in OA pathogenesis. As currently prescribed OA drugs are addressing OA symptoms,our results highlight a potential novel treatment strategy whereby inhibitors of calcium- containing crystal formation and IL-6 could be combined to form the basis of a disease modifying treatment and alter the course of OA.

New insight in the relationship between regional patterns of knee cartilage thickness, osteoarthritis disease severity, and gait mechanics.

To test if the relationship between knee kinetics during walking and regional patterns of cartilage thickness is influenced by disease severity we tested the following hypotheses in a cross-sectional study of medial compartment osteoarthritis (OA) subjects: (1) the peak knee flexion (KFM) and adduction moments (KAM) during walking are associated with regional cartilage thickness and medial-to-lateral cartilage thickness ratios, and (2) the associations between knee moments and cartilage thickness data are dependent on disease severity. Seventy individuals with medial compartment knee OA were studied. Gait analysis was used to determine the knee moments and cartilage thickness was measured from magnetic resonance imaging. Multiple linear regression analyses tested for associations between cartilage thickness and knee kinetics. Medial cartilage thickness and medial-to-lateral cartilage thickness ratios were lower in subjects with greater KAM for specific regions of the femoral condyle and tibial plateau with no associations for KFM in patients of all disease severities. When separated by severity, the association between KAM and cartilage thickness was found only in patients with more severe OA, and KFM was significantly associated with cartilage thickness only for the less severe OA subjects for specific tibial plateau regions. The results support the idea that the KAM is larger in patients with more severe disease and the KFM has greater influence early in the disease process, which may lessen as pain increases with disease severity. Each component influences different regions of cartilage. Thus the relative contributions of both KAM and KFM should be considered when evaluating gait mechanics and the influence of any intervention for knee OA.

Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis.

OBJECTIVES: Basic calcium phosphate (BCP) crystal and interleukin 6 (IL-6) have been implicated in osteoarthritis (OA). We hypothesise that these two factors may be linked in a reciprocal amplification loop which leads to OA. METHODS: Primary murine chondrocytes and human cartilage explants were incubated with hydroxyapatite (HA) crystals, a form of BCP, and the modulation of cytokines and matrix-degrading enzymes assayed. The ability of IL-6 to stimulate chondrocyte calcification was assessed in vitro. The mechanisms underlying the effects of HA on chondrocytes were investigated using chemical inhibitors, and the pathways mediating IL-6-induced calcification characterised by quantifying the expression of genes involved in chondrocyte mineralisation. The role of calcification in vivo was studied in the meniscectomy model of murine OA (MNX), and the link between IL-6 and cartilage degradation investigated by histology. RESULTS: In chondrocytes, BCP crystals stimulated IL-6 secretion, further amplified in an autocrine loop, through signalling pathways involving Syk and PI3 kinases, Jak2 and Stat3 molecules. Exogenous IL-6 promoted calcium-containing crystal formation and upregulation of genes involved in calcification: the pyrophosphate channel Ank, the calcium channel Annexin5 and the sodium/phosphate cotransporter Pit-1. Treatment of chondrocytes with IL-6 inhibitors significantly inhibited IL-6-induced crystal formation. In meniscectomised mice, increasing deposits of BCP crystals were observed around the joint and correlated with cartilage degradation and IL-6 expression. Finally, BCP crystals induced proteoglycan loss and IL-6 expression in human cartilage explants, which were reduced by an IL-6 inhibitor. CONCLUSIONS: BCP crystals and IL-6 form a positive feedback loop leading to OA. Targeting calcium-containing crystal formation and/or IL-6 are promising therapeutic strategies in OA.

Octacalcium Phosphate (OCP) Crystals Induce Synovial Inflammation and Cartilage

Introduction: The presence of intra-articular basic calcium phosphate (BCP) crystals, including OCP, carbonated-apatite, hydroxyapatite and tricalcium phosphate crystals, is associated with severe osteoarthritis and destructive arthropathies such as Milwaukee shoulder. Although BCP crystals displayed, in vitro, mitogenic, anabolic and catabolic responses, their intra-articular effect was never assessed.Objective: To determine the effects of OCP crystals in joints in vivo.Methods: OCP crystals (200 ug in 20 ml PBS) were injected into the right knee joint (the contra-lateral knee joint injected with 20 ul of PBS serving as a control) of wild-type mice treated or not by the IL1R antagonist Anakinra or mice deficient for the inflammasome proteins ASC and NALP3. 4 days and 17 days after crystal injection, mice were sacrificed and knee joints dissected. Histological scoring for synovial inflammation and characterisation of macrophages, neutrophils and T cells were performed. Technetium (Tc) uptake was measured at 6h, 1 and 4 days after OCP injection. Cartilage degradation was evaluated by Safranin O staining and VDIPEN immunohistochemistry. Intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining.Results: The intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining performed on non-decalcified samples embedded in methyl-metacrylate. Injection of OCP crystals into knee joints led at day 4 to an inflammatory response with intense macrophage staining and also some neutrophil recruitment in the synovial membrane. This synovitis was not accompanied by increased Tc uptake into the knee joint, Tc uptake being similar in OCP crystal injected knee or control knee at all time points investigated (6h, 1 day, 4 days). The histological modifications persisted over 17 days, with an additional fibrosis evidenced at this later time-point. The OCP crystal-induced synovitis was totally IL-1a and IL-1 independent as shown by the absence of inhibitory effects of anakinra injected into wild-type mice. Accordingly, OCP crystal-induced synovitis was similar in ASC-/- and NALP3-/- mice as no alterations of inflammation were demonstrated between these mice groups. Concerning cartilage matrix degradation, OCP crystals induced a strong breakdown of proteoglycans 4 and 17 days after injection, as measured by loss of red staining from Safranin O-stained sections of cartilage surfaces. In addition, we also measured advanced cartilage matrix destruction mediated by MMPs, as evidenced by VDIPEN staining of cartilage. OCP-mediated cartilage degradation was similar in all experimental conditions tested (WT+Anakinra, or ASC or NALP3 deficient mice).Conclusion: These data indicate in vivo that the intra-articular presence of OCP crystals is associated with cartilage destruction along with synovial inflammation. This is an interesting and new model of destructive arthropathy related to BCP crystals which will allow to assess new therapies in this disease.

Traitement de la coxarthrose par des prothèses totales de hanche sur mesure [Treatment of coxarthrosis with fitted total hip prostheses replacement]

The treatment of hip osteoarthritis with total hip arthroplasty has continuously evolved since it was first introduced in the sixties. The problem of aseptic loosening of the cemented prostheses, mainly in young active patients, has stimulated two different types of research: on one side the improvement of cementing techniques and on the other side the development of cementless osteoinegrable implants. We discuss the problems of these cementless hip prostheses. Recently published anatomic and biomechanic studies have led to the development of personalized custom femoral stems for each patient. The conception technique and first clinical results are described.

Multi-segment foot kinematics after total ankle replacement and ankle arthrodesis during relatively long-distance gait.

This study aimed to investigate the influence of ankle osteoarthritis (AOA) treatments, i.e., ankle arthrodesis (AA) and total ankle replacement (TAR), on the kinematics of multi-segment foot and ankle complex during relatively long-distance gait. Forty-five subjects in four groups (AOA, AA, TAR, and control) were equipped with a wearable system consisting of inertial sensors installed on the tibia, calcaneus, and medial metatarsals. The subjects walked 50-m twice while the system measured the kinematic parameters of their multi-segment foot: the range of motion of joints between tibia, calcaneus, and medial metatarsals in three anatomical planes, and the peaks of angular velocity of these segments in the sagittal plane. These parameters were then compared among the four groups. It was observed that the range of motion and peak of angular velocities generally improved after TAR and were similar to the control subjects. However, unlike AOA and TAR, AA imposed impairments in the range of motion in the coronal plane for both the tibia-calcaneus and tibia-metatarsals joints. In general, the kinematic parameters showed significant correlation with established clinical scales (FFI and AOFAS), which shows their convergent validity. Based on the kinematic parameters of multi-segment foot during 50-m gait, this study showed significant improvements in foot mobility after TAR, but several significant impairments remained after AA.

Ambulatory measurement of ankle kinetics for clinical applications.

This study aimed to design and validate the measurement of ankle kinetics (force, moment, and power) during consecutive gait cycles and in the field using an ambulatory system. An ambulatory system consisting of plantar pressure insole and inertial sensors (3D gyroscopes and 3D accelerometers) on foot and shank was used. To test this system, 12 patients and 10 healthy elderly subjects wore shoes embedding this system and walked many times across a gait lab including a force-plate surrounded by seven cameras considered as the reference system. Then, the participants walked two 50-meter trials where only the ambulatory system was used. Ankle force components and sagittal moment of ankle measured by ambulatory system showed correlation coefficient (R) and normalized RMS error (NRMSE) of more than 0.94 and less than 13% in comparison with the references system for both patients and healthy subjects. Transverse moment of ankle and ankle power showed R>0.85 and NRMSE<23%. These parameters also showed high repeatability (CMC>0.7). In contrast, the ankle coronal moment of ankle demonstrated high error and lower repeatability. Except for ankle coronal moment, the kinetic features obtained by the ambulatory system could distinguish the patients with ankle osteoarthritis from healthy subjects when measured in 50-meter trials. The proposed ambulatory system can be easily accessible in most clinics and could assess main ankle kinetics quantities with acceptable error and repeatability for clinical evaluations. This system is therefore suggested for field measurement in clinical applications.

Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.

BACKGROUND: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. Objective: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. METHODS: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. RESULTS: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. CONCLUSIONS: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.