Knee Joint Destruction Research Articles

Synergic effect of combined xenogeneic mesenchymal stem cells and ceftriaxone on acute septic arthritis.

This study tested the hypothesis that combined ceftriaxone (Cef) and human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) was better than either therapy for alleviating acute septic arthritis (ASA). Adult-male C57BL/6 mice were categorized into control group (Clt), group A (ASA only), group B [ASA + Cef (5 mg/kg, IM per day, at days 2 to 16 after ASA induction)], group C [ASA + HUCDMSCs (5 × 105 per mice at days 2, 3, 4 after ASA induction)], and group D (ASA + Cef + HUCDMSCs). Animals were euthanized by day 28. The result demonstrated that the body weight was significantly lower, whereas the ratio of kidney or spleen weight to WB, circulatory WBC count, bacterial colony-formation-unit from circulatory/kidney extraction were significantly higher in group A than in other groups (all P < .001). The proinflammatory cytokines (IL-6/TNF-α) of knee joint fluid were lowest in Clt and significantly and progressively reduced from groups A to D, whereas the circulatory levels of these 2 parameters at the time points of days 3/7/28 exhibited an identical pattern as knee joint fluid among the groups (all P-value < .0001). The scores of vertebral-bone destructions/inflamed synovium were lowest in Clt, highest in group A, significantly higher in group C than in groups B/D, and significantly higher in group C than in group D (all P < .0001). Combined antibiotics and Cef and HUCDMSCs was superior to just one therapy for suppressing circulatory and tissue levels of inflammation and knee joint destruction in ASA.

Changes in knee joint destruction patterns among patients with rheumatoid arthritis undergoing total knee arthroplasty in recent decades.

This study aimed to investigate the trend of joint destruction patterns on knee radiographs of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) over the past 16years. Medial joint space, lateral joint space, medial spur area, lateral spur area (L-spur), and femoro-tibial angle were obtained from 831 preoperative knee radiographs of patients with RA who underwent TKA between 2006 and 2021 using software capable of automatic measurements. Non-hierarchical clustering was performed based on these five parameters. Trends in the five individual radiographic parameters and the ratio of each cluster were investigated during the target period. Moreover, clinical data from 244 cases were compared among clusters to identify factors associated with this trend. All parameters, except for L-spur, showed significant increasing trends from 2006 to 2021. The radiographs were clustered into groups according to the characteristic pattern of radiographic findings: cluster 1 (conventional RA type), with bicompartmental joint space narrowing (JSN), less spur formation, and valgus alignment; cluster 2 (osteoarthritis type), with medial JSN, medial osteophytes, and varus alignment; and cluster 3 (less destructive type), with mild bicompartmental JSN, less spur formation, and valgus alignment. The ratio of cluster 1 showed a significantly decreasing trend contrary to the significantly increasing trend in clusters 2 and 3. The DAS28-CRP of cluster 3 was higher than those of clusters 1 and 2. Radiographs of TKA recipients with RA are increasingly presenting osteoarthritic features in recent decades. Key Points • Using automated measurement software, morphological parameters were measured from radiographs of 831 patients with rheumatoid arthritis who had undergone TKA in the past 16years. • Cluster analysis based on the radiographic parameters revealed that the radiographs of patients with end-stage knee arthritis requiring total knee arthroplasty were classified into three groups. • In patients with rheumatoid arthritis who have undergone total knee arthroplasty in the past 16years, the proportion of clusters with features of osteoarthritis and difficult-to-treat rheumatoid arthritis has increased, while the proportion of conventional rheumatoid arthritis has decreased.

Surgery for chronic arthropathy in people with haemophilia.

Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the absence or deficiency of a clotting factor protein. Staging classifications, such as the Arnold-Hilgartner classification for haemophilic arthropathy of the knee, radiologically reflect the extent of knee joint destruction with underlying chronic synovitis. Management of this highly morbid disease process involves intensive prophylactic measures, and chemical or radioisotope synovectomy in its early stages. However, failure of non-surgical therapy in people with progression of chronic arthropathy often prompts surgical management, including synovectomy, joint debridement, arthrodesis, and arthroplasty, depending on the type of joint and extent of the damage. To date, management of people with mild to moderate chronic arthropathy from haemophilia remains controversial; there is no agreed standard treatment. Thus, the benefits and disadvantages of non-surgical and surgical management of mild to moderate chronic arthropathy in people with haemophilia needs to be systematically reviewed. OBJECTIVES: To assess the efficacy and safety of surgery for mild to moderate chronic arthropathy in people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, and two trial registers to August 2022. We also handsearched relevant journals and conference abstract books. Randomized controlled trials (RCTs) and quasi-RCTs comparing surgery and non-surgical interventions, for any joint with chronic arthropathy, in people with haemophilia, who were at least 12 years old. The review authors did not identify any trials to include in this review. The review authors did not identify any trials to include in this review. The review authors did not identify any trials to include in this review. Due to a lack of research in this particular area, we plan to update the literature search every two years, and will update review if any new evidence is reported. There is a need for a well-designed RCT that assesses the safety and efficacy of surgical versus non-surgical interventions for chronic arthropathy in people with haemophilia.

Repurposing an anti-epilepsy glutamate receptor antagonist for the prevention of post-traumatic osteoarthritis

Purpose: Osteoarthritis (OA) affects 27 million people in the US and has no disease modifying treatments. Since joint injuries lead to OA, intervention at the time of injury could prevent injury-induced OA. Synovial fluid (SF) glutamate concentrations increase in arthritis. We previously found that activation of kainate (KA) and AMPA glutamate receptors (GluRs) increases interleukin-6 release and causes pain, that AMPA and KA GluRs localise to osteoarthritic bone, cartilage and synovium and that NBQX (AMPA/KA GluR antagonist) reduces knee swelling, gait abnormalities and joint destruction in a rat inflammatory arthritis model, and two models of post-traumatic OA (PTOA): rat medial meniscal transection (MNX), mouse anterior cruciate ligament (ACL) rupture.

A Novel Phytochemical, DIM, Inhibits Proliferation, Migration, Invasion and TNF-α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway.

In rheumatoid arthritis(RA) pathogenesis, activated RA fibroblast-like synoviocytes (RA-FLSs) exhibit similar proliferative features as tumor cells and subsequent erosion to cartilage will eventually lead to joint destruction. Therefore, it is imperative to search for compounds, which can effectively inhibit the abnormal activation of RA-FLSs, and retard RA progression.3′3-Diindolylmethane (DIM), the major product of the acid-catalyzed oligomerization of indole-3-carbinol from cruciferous vegetables, has been reported to be functionally relevant to inhibition of migration, invasion and carcinogenesis in some solid tumors. In this study, we explored the anti-proliferation, anti-metastasis and anti-inflammation effects of DIM on RA-FLSs as well as the underlying molecular mechanisms. To do this, primary RA-FLSs were isolated from RA patients and an animal model. Cell proliferation, migration and invasion were measured using CCK-8, scratch, and Transwell assays, respectively. The effects of DIM on Matrix metalloproteinases (MMPs) and some inflammatory factors mRNA and key molecules such as some inflammatory factors and those involved in aberrantly-activated signaling pathway in response to tumor necrosis factor α(TNF-α), a typical characteristic mediator in RA-FLS, were quantitatively measured by real-time PCR and western blotting. Moreover, the effect of DIM on adjuvant induced arthritis(AIA) models was evaluated with C57BL/6 mice in vivo. The results showed that DIM inhibited proliferation, migration and invasion of RA-FLS in vitro. Meanwhile, DIM dramatically suppressed TNF-α–induced increases in the mRNA levels of MMP-2, MMP-3, MMP-8, and MMP-9; as well as the proinflammatory factors IL-6, IL-8, and IL-1β. Mechanistic studies revealed that DIM is able to suppress phosphorylated activation not only of p38, JNK in MAPK pathway but of AKT, mTOR and downstream molecules in the AKT/mTOR pathway. Moreover, DIM treatment decreased expression levels of proinflammatory cytokines in the serum and alleviated arthritis severity in the knee joints of AIA mice. Taken together, our findings demonstrate that DIM could inhibit proliferation, migration and invasion of RA-FLSs and reduce proinflammatory factors induced by TNF-α in vitro by blocking MAPK and AKT/mTOR pathway and prevent inflammation and knee joint destruction in vivo, which suggests that DIM might have therapeutic potential for RA.

Correlation between the effect of increasing body weight with plantar pressure and ankle-knee radiographic angle parameters changes

Background: Understanding the biomechanical structure of the body is important to preventing and treating the musculoskeletal system problems. The increase in body mass index contributes to the elevated peak plantar pressure and decreased longitudinal arch of the foot. This condition, consequently, may cause mal-alignment of the lower extremity, leading to promote cartilage breakdown, osteophyte formation, subchondral bone hypertrophy, lead to progression of knee joint destruction and functional deficits. Objective: The aim of the study was to examine the correlation between body weight, plantar pressures, ankle and knee angle measurement parameters. Methods: The research study sample included 30 female who met inclusion and exclusion criteria. In order to evaluate the structural characteristic of plantar foot, we used the blueprint method on bare-foot and also when carrying 15 and 25 kilogram of load. Furthermore, to measure knee-angle parameters, we also performed a bilateral standing radiograph approach of lower extremity. Results: This study showed a significant correlation between BMI/Body mass index and HW/heel width (p = 0,00) with low positive correlation for both sides. Furthermore, BMI and PAW/plantar arch width (p = 0,00) showed a moderate positive correlation for both sides. In contrast to that, BMI and MFA/mid-foot area (p = 0,00) showed a moderate positive correlation for the right side but low positive correlation for the left side. Another measurement such as BMI and AI/arch index (p = 0,00) had a strong positive correlation on the right side and moderate positive correlation on the left side. Moreover, BMI and AAL/Ankle angle alignment (p = 0,00) revealed a strong positive correlation for both sides, BMI and XCTP/trans-condylar tibial plateau angle (p < 0,05) had a low positive correlation for both sides, meanwhile BMI and AA/ankle angle (p = 0,00) showed a low positive correlation for both sides. Conclusion: Increasing axial load was statistically significant correlated with increasing plantar pressure and ankle-knee radiographic angle parameter. The results also revealed that increasing axial load was found to have strong correlation to the arch index (AI) and ankle angle alignment (AAL). It was a compensatory phenomenon, which can cause structural disturbances and function of the lower limb.

Repurposing glutamate receptor antagonists to prevent post-traumatic osteoarthritis

Purpose: Synovial fluid glutamate concentrations increase in arthritis and after joint injury. Activation of kainate (KA) and AMPA glutamate receptors (GluRs) increase interleukin-6 release by synoviocytes and cause joint pain. We previously found that AMPA and KA GluRs localise to osteoarthritic bone, cartilage and synovium and that NBQX (AMPA/KA GluR antagonist) reduced knee swelling, gait abnormalities and joint destruction in a rat inflammatory arthritis model and two models of post-traumatic osteoarthritis: rat medial meniscal transection (MNX), mouse non-invasive anterior cruciate ligament (ACL) rupture. Since NBQX is not approved for use in humans, we have tested 4 AMPA/KA GluR antagonists (anonymised to A, B, C and D), which have passed Phase 1 clinical trials, and compared these to current approved treatments: hyaluronic acid (HA) and steroid intra-articular injections. HA and steroids have not previously been tested in rodent models intra-articularly at the time of injury. We hypothesise that drugs A-D will reduce pain, inflammation and degeneration in the mouse ACL rupture post-traumatic osteoarthritis model. Methods: The right stifle of 12-week-old C57Bl6 mice was held in flexion and a 12N load (ElectroForce® 3200, BOSE) applied under anaesthetic until ACL rupture (in accordance with Animals (Scientific Procedures) Act 1986. Project License number: P287E87DF). A single 10μl intra-articular injection of drug A (n=4), B (n=3), C (n=3), D (n=4), hyaluronic acid (HA) (n=8, Durolane, 8mg/kg, Bioventus) or steroid (n=7, Depo-medrone, 10mg/kg, Pfizer) was administered to mice immediately following ACL rupture, whilst additional mice received an intra-articular injection of vehicle (100mM NaOH vehicle for drug A, n=4; DMSO vehicle for drugs B, C and D, n=4; saline for HA and steroid, n=7) immediately following ACL rupture. Contralateral knees (intact ACL) were used as controls. All mice received analgesia (Temgesic) prior to ACL-rupture. Over 21 days, lameness was scored and stifle swelling measured (electronic calipers, mean of 3 measurements, days 0, 1, 2, 3, 7, 14, 21). On day 21, all animals were culled and knees scored for degradation (OARSI score). Measurements are mean of 2 observers blinded to treatment. Results: By day 2, drug A had reduced mean knee swelling by ∼50% and did not differ significantly from day 0 pre-ACL rupture measurements, whereas vehicle control knee swelling was significantly increased until day 7 (p<0.01, general linear model (GLM)) (Fig. 1a). Drug C also reduced knee swelling to day 0 levels by day 2, whereas drug D (p<0.05, GLM) and vehicle control (p<0.001, GLM) were significantly increased until day 7. Drug B did not reduce swelling until day 14 (Fig. 1b). On day 1, steroid injection significantly reduced knee swelling (∼50% reduction) compared to vehicle (p<0.001, GLM) and HA (p<0.05, GLM), but this was short-lived with no reductions from day 2 onwards (Fig. 1c). HA did not reduce knee swelling (Fig. 1c). Lameness scores were reduced by drugs A-D, with significant reductions compared to vehicle control (4.13±0.13) on day 3 by drug B (1.83±0.17, p<0.001, GLM), drug C (2.33±0.6, p<0.05, GLM) and drug D (2.5±0.2, p<0.05, GLM). HA and steroid injections did not significantly reduce lameness at any time point. Drug A showed ∼40% reduction in mean degradation score at day 21, whereas HA had no effect and depo-medrone significantly increased degeneration by ∼50% (p<0.05, one-way ANOVA). Conclusions: This study provides evidence that AMPA/KA GluR antagonists, already approved for use in humans, relieve inflammation, lameness and joint degradation in post-traumatic OA. GluR antagonists exceeded anti-nociceptive and anti-inflammatory effects of HA and steroids. Drugs A and C reduced knee swelling to control levels by day 2, whereas HA did not reduce swelling at all, and steroid effects were not apparent beyond day 1. All GluR antagonists reduced lameness scores whereas HA or steroid injections did not. Drug A reduced mean degeneration whereas HA had no effect and depo-medrone significantly increased degeneration. An estimated 52.5 million adults in the United States are reported to have some form of arthritis, with OA (approximately 27 million) being the most prevalent (Centers for Disease Control and Prevention). Joint injuries, such as ACL rupture or meniscal tear, are extremely common, with 50-90% of these patients going on to develop OA within 5-15 years. There is currently no cure for OA and where pain/disability is intolerable, joint replacement is performed. Surgery is costly, carries significant risks, with 20% of knee replacements unsuccessful. Although not yet fully powered, our data indicate that AMPA/KA GluR antagonists, already approved for human use, have exciting potential for rapid repurposing as new disease modifying drugs to prevent and treat OA.

Investigation of protein content of synovial fluids with DSC in different arthritides

In the case of joint diseases, as a result of the process induced by the pathophysiological factors, the small articular structures that have pilled result in a qualitative and quantitative modification of the composition of the synovial fluid (SF). The analysis of this fluid offers a unique opportunity to study the joint diseases. In our study, 28 cases of acute knee joint meniscus injuries, transient knee joint synovitis, or degenerative knee joint destruction were studied. Following the collection and storage of SF, removed on the basis of the sample collection protocol, they were denatured in a SETARAM Micro DSC-II calorimeter with a scanning rate 0.3 K min−1 in the 20–90 °C temperature range. 4–4 samples from the “normal” SF batch were inoculated by two different strains of bacteria [Staphylococcus aureus and Staphylococcus epidermidis] with 10−3 colony-forming unit. Thermoanalytical changes of the proteins found in the SF were studied by a SETARAM Micro DSC-II, in the laboratory of the Biophysical Institute. The maximum denaturation temperature of the proteins being in the SF with different severity varied according to the criterion of the radiological scaling of osteoarthritis made by the Kellgren–Lawrence criterion. The decomposition of the scans showed the degree of the damage in case of SF as well as in the inoculated samples. Knowing the denaturing properties of temperature-dependent protein molecules in SF, DSC can be used to design and develop intra-articular lubricant additives that effectively enhance protein stability and contribute to a reduction in joint wear.

Smoothness of the knee joint movement during the stance phase in patients with severe knee osteoarthritis

BackgroundPatients with knee osteoarthritis can significantly affect the function of the knee joint in terms of joint range and mobility and have a stereotypical pattern of knee stiffness during gait, caused by an increased resistance in the muscles and soft tissues during the stance phase of knee joint movement. Smoothness in movement, such as during walking and running, is assumed to be attained by adulthood; however, disruptions in gait pattern due to injury or performance enhancement can alter the smoothness of the movement, and this is often quantified in terms of “jerk”. A higher jerk value is linked with a decrease in smoothness. However few have reported to evaluate the smoothness of the knee joint movement during walking in patients with knee osteoarthritis. The purpose of the present study was to quantify the smoothness of the knee joint movement during walking in people with knee osteoarthritis. MethodsPatients were classified as having early or severe knee osteoarthritis. There were eight patients in each group (16 knees; three males, five females). The normalized angular jerk was calculated as an indicator of the walking knee joint smoothness in each of the four periods of the stance phase. Two-way ANOVA was performed to compare the smoothness of knee joint movement between groups and between each period of the stance phase. ResultsThe angular change in the sagittal plane of those with severe knee osteoarthritis was smaller than that of those with early knee osteoarthritis in all periods of the stance phase. Normalized angular jerk did not significantly differ between groups in all periods. In both groups, the normalized angular jerk in the sagittal plane was significantly larger in the mid-stance and terminal stance periods than in the early stance and pre-swing periods. Only in patients with severe knee osteoarthritis, there was a significantly larger jerk in the frontal plane in the mid-stance period. ConclusionThe present results revealed that the smoothness of joint movement decreases during the single leg supporting phase of the stance phase in the frontal plane with severe knee osteoarthritis, although there is no difference in smoothness of joint movement according to the severity of knee osteoarthritis The instability during single leg support due to increase of the knee joint load and destruction cause the impaired smoothness of the knee joint movement.

Assessing joint destruction in the knees of patients with rheumatoid arthritis by using a semi-automated software for magnetic resonance imaging: therapeutic effect of methotrexate plus etanercept compared with methotrexate monotherapy

Objectives: To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated software for magnetic resonance imaging (MRI) scan analysis.Materials and methods: This study enrolled patients with active moderate-to-severe RA who displayed an inadequate response to oral MTX at screening. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (≥10 mg/week). The primary endpoint was the quantitative knee cartilage volume using our software developed for MRI scan analysis.Results: A total of 18 female patients were enrolled in this study and allocated to the MTX + ETN group (n = 9) or the MTX monotherapy group (n = 9). At 52 weeks, the quantitative knee cartilage volume was significantly reduced compared with baseline in both groups (MTX plus ETN group: 2.3 ± 2.3 cm3; MTX monotherapy group: 2.4 ± 1.6 cm3); however, the difference was not significant.Conclusion: The semi-automated software for MRI scan analysis can reveal useful and potentially clinically important information about the characteristics of knee joint destruction in patients with RA.

Total knee replacement with tibial tubercle osteotomy in rheumatoid patients with stiff knee.

Total knee arthroplasty (TKA) is a well-proven modality that can provide pain relief and restore mobility for rheumatoid arthritis (RA) patients with advanced joint destruction. Patellar ligament avulsion, especially in presence of poor bone quality and knee stiffness, is one of the special considerations that must be addressed in this unique population of patients. This study aimed to determine the functional results in a series of rheumatoid patients with stiff knee and end-stage joint destruction who underwent tibial tubercle osteotomy during TKA. Twenty-three knees in 20 patients (16 women; four men) at a mean age of 54years with end-stage arthritis and knee stiffness due to RA were operated upon for TKA using tibial tubercle osteotomy as a step during the operation. Patients were reviewed clinically and radiographically with a minimum follow-up of twoyears. Complications were noted. Hospital for Special Surgery (HSS) score was recorded pre-operatively and at six and 12months postoperatively. Union occurred at the osteotomy site in 21 of 23 cases. One case had deep venous thrombosis (DVT). There was no infection or periprosthetic fracture, and at last follow-up, no patient required revision. HSS score improved from 46 (15-60) pre-operatively to 85 (71-96) post-operatively. Tibial tubercle osteotomy during TKA in patients with RA and stiff knee is technically demanding yet proved to be effective in improving post-operative range of movement and minimising the complication of patellar ligament avulsion.

Insulin-Like Growth Factor II (IGF-II) Inhibits IL-1β-Induced Cartilage Matrix Loss and Promotes Cartilage Integrity in Experimental Osteoarthritis.

Osteoarthritis (OA) is a widespread chronic joint disease characterized by articular cartilage destruction and accompanied by pain and disability. In this study, we found that the expression of Insulin-like Growth Factor II (IGF-II) was reduced in articular cartilage in human OA patients as well as in the murine experimental OA model of destabilization of the medial meniscus (DMM). In primary human articular chondrocytes, ectopic expression of lentiviral IGF-II inhibited pro-inflammatory cytokine IL-1β-induced NF-κB activation as well as catabolic gene expression. Interestingly, IGF-II did not significantly alter the phosphorylation states of ERK1/2 or Akt, which are kinases typically activated by IGF-I. Instead, it induced the activity of phospholipase C (PLC) and a PLC inhibitor blocked the inhibitory activity of IGF-II against IL-1β, suggesting that this activity is mediated through PLC. Furthermore, IGF-II increased cartilage matrix levels and decreased MMP13 protein expression in explanted human OA cartilage cultures in vitro. In the in vivo DMM model, intraarticular injection of lentiviral IGF-II led to enhanced cartilage matrix levels and decreased MMP13 protein expression, as well as reduced osteophyte formation and subchondral bone sclerosis. Therefore, our results suggest that IGF-II can promote cartilage integrity and halt knee joint destruction in OA.

FRI0241 Assessment of Joint Destruction at the Knee in Rheumatoid Arthritis Using Semi-Automated Software for Magnetic Resonance Image Analysis

BackgroundMagnetic resonance (MR) imaging is widely used to assess the joints of patients with rheumatoid arthritis (RA).ObjectivesTo evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX)...

SAT0154 MRI evaluation of the knees in assessing rhuematoid arthritis patients on etanercept

BackgroundBiologics improved Rheumatoid Arthritis (RA) treatment dramatically and we have abundant evidence on its high efficacy, especially on preventing joint destruction. However, we do not have enough evidence on its...

Myofascial trigger point, falls in the elderly, idiopathic knee pain and osteoarthritis: An alternative concept

Knee malalignment and associated pathological abnormal forces transmitted through the knee is thought to provoke joint protective mechanism in reflex arthrogenous muscle inhibition (AMI) and the start of the idiopathic knee osteoarthritis process. The current prevailing hypothesis is AMI initiates quadriceps muscle weakness, cause aberrant loading of the knee joint and focal cartilage destruction. This paper investigates for evidence in the literature if this conceptual framework is consistent with the clinical evidence, and if there is an alternative explanation to AMI hypothesis for the pathogenesis of idiopathic knee osteoarthritis.One crucial question yet to be answered by the AMI hypothesis is; where are the initial aggravating factors of reflex AMI emanate from? AMI hypothesis relies on joint damage and changes in joint homeostasis to provoke a reflex arthrogenous response which can be found later in the development of knee OA. Myofascial trigger point (MTrP) hypothesis only relies on muscle tightness, pain and weakness to detect early pathological neuromuscular changes including knee instability and falls in the elderly.AMI is implicated in the knee OA pathological process but much later on when there are changes in joint homeostasis and joint cartilage damage have occurred. Falls in the elderly is a result of early pathological neuromuscular changes. The MTrP hypothesis is more sensitive and advanced in the early detection of neuromuscular impairment and pathological changes, allowing early intervention, prevention of falls in the elderly and idiopathic knee osteoarthritis.

Knee joint destruction driven by residual local symptoms after anti-tumor necrosis factor therapy in rheumatoid arthritis

In patients with rheumatoid arthritis who had symptomatic knee joints at the start of anti-tumor necrosis factor (TNF) therapy, the relationship between local symptoms and knee joint destruction at 94 weeks was retrospectively investigated. Among the patients with rheumatoid arthritis and received anti-TNF therapy, the 32 patients (52 joints) having swollen and/or tender knee joints were included in this study. Changes of disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) and knee joint destruction using Larsen's grading system 94 weeks after anti-TNF therapy were evaluated. Furthermore, the differences of the DAS28-CRP, swollen and tender knee joints between the patients who showed progression of joint destruction (Progression group) and those who did not (Non-progression group) were investigated. DAS28-CRP showed time-dependent, favorable results. However, progression of joint destruction was observed in 12 out of 52 joints. DAS28-CRP at 0 and 94 weeks after anti-TNF therapy were not different between Progression and Non-progression groups. However, the rate of swollen knee joints was higher in Progression group from 0 week. In addition, the ratio of swollen and/or tender knee joints was higher in Progression group from 22 to 94 weeks after anti-TNF therapy. The disease activity evaluated using DAS28-CRP was improved by anti-TNF therapy, but residual local symptoms in the knee joints were associated with a high incidence of joint destruction progression. We should treat rheumatoid arthritis patients with consideration for the possibility of joint destruction in the knee joints having residual local symptoms to progress.

Prevention of knee joint destruction in rheumatoid patients treated with Infliximab

Prevention of knee joint destruction in rheumatoid patients treated with Infliximab

Replacement arthroplasty for patients with rheumatoid arthritis

Replacement arthroplasty is an excellent method to improve activities of daily living (ADL) and quality of life (QOL) in patients with rheumatoid arthritis (RA) . In many cases of RA, prosthetic surgery is carried out on multiple joints. When prosthetic surgery is performed in cases with severe knee contracture or joint destruction, surgical invasion can be extensive. Regarding timing of surgery, it is better while the joint is still somewhat intact, and as long as the operability conditions can be met, age is irrelevant. It is important not to delay the timing of surgery. This article mainly considers total knee arthroplasty (TKA).

Suppression of pain and joint destruction by inhibition of the proteasome system in experimental osteoarthritis

Osteoarthritis is a degenerative joint disease with pain and loss of joint function as major pathological features. Recent studies show that proteasome inhibitors reduce pain in various pathological conditions. We evaluated the effects of MG132, a reversible proteasome inhibitor on pain and joint destruction in a rat model of osteoarthritis. Osteoarthritis was induced by intraarticular injection of monosodium iodoacetate into the rat knee. Knee joint stiffness was scored and nociception was evaluated by mechanical pressure applied to the respective hind paw. Knee joint destruction was assessed by radiological and histological analyses. Expression of matrix metalloproteinase-3 (MMP-3) was analyzed by quantitative reverse transcription polymerase chain reaction in the knee articular cartilage. Expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was studied in the dorsal root ganglia (L4–L6) by quantitative reverse transcription polymerase chain reaction and in the knee joints by immunohistochemistry. Our results indicate that daily treatment of osteoarthritic rats with MG132 significantly increases their mobility while the swelling, pain thresholds, and pathological features of the affected joints were reduced. Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the arthritic rats was normalized by MG132 administration. We conclude that the proteasome inhibitor MG132 reduces pain and joint destruction, probably by involving the peripheral nervous system, and that changes in SP and CGRP expression correlate with alterations in behavioural responses. Our findings suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy for osteoarthritis.

Total Knee Arthroplasty in a Patient with Erdheim-Chester Disease with Massive Joint Destruction

Erdheim-Chester disease was named after William Chester, who described the disease in 1930, and the Viennese pathologist Jakob Erdheim. Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis that causes a systemic disease with involvement of the tubular long bones, sparing the axial skeleton, as well as the hands and feet1. The prognosis depends in large part on the extent and distribution of extraosseous manifestations, which most commonly includes diabetes insipidus; these manifestations can also include involvement of the retroperitoneum, skin, lung, and heart and include painless bilateral exophthalmus in >50% of cases2-4. Together with bone pain that arises from bone destruction affecting nociceptors within periosteum and bone marrow, mainly of the lower limbs, these clinical symptoms lead to the diagnosis of Erdheim-Chester disease. The diagnosis is usually based on typical radiographic findings, with symmetric bilateral osteosclerosis involving metaphyseal and diaphyseal regions of the long bones with sparing of the epiphyses. Bone scintigraphy reveals increased tracer uptake in Erdheim-Chester disease lesions, while magnetic resonance imaging shows replacement of the normal fatty bone marrow as well as periostitis2-6. Our report highlights a case of severe bilateral knee joint destruction and varus deformity in a fifty-eight-year-old man with Erdheim-Chester disease and describes the clinical details, technical aspects of surgery, and short-term outcome one year after surgery. To our knowledge, this is the first report of a joint arthroplasty (specifically, bilateral total knee replacement) in a patient with Erdheim-Chester disease. The patient was informed that data concerning the case would be submitted for publication, and he consented. This fifty-eight-year-old male winegrower with a body-mass index of 39.5 kg/m2 and a five-year history of Erdheim-Chester disease developed progressive motion-dependent pain and varus deformity in both knees two years prior to presentation. There was no …