Bone Erosion Research Articles

Radiological features of Stafne mandibular bone cavity in panoramic image and cone beam computed tomography

BackgroundStafne mandibular bone cavity (SMBC) is an asymptomatic radiolucent lesion observed in the mandible on X-ray images, with well-defined borders. This lesion does not require treatment, and size changes are very rare. The purpose of this article is to summarize the radiological and clinical features of SMBC, aiming to prevent misinterpretation of this benign lesion as other pathologies and aid in differential diagnosis within the field of dental practice.MethodsA total of 32 patients who visited our hospital and were radiologically diagnosed with SMBC based on cone-beam computed tomography (CBCT) and panoramic images between 2005 and 2021 were included in this study. Among them, surgical intervention was performed in one case. Gender and age distribution of the patients, radiographic location and size of the lesion, relationship with the mandibular canal in CBCT, presence of cortical bone erosion in the mandibular lingual area in panoramic images, and the amount of residual cortical bone on the affected side in CBCT were investigated.ResultPatients were 26 men (81.3%) and 6 women, with a mean age of 54.3 years. The average horizontal and vertical length was 16.6 mm and 10.6 mm. Out of a total of 32 cases, 29 cases were found in the posterior region of the mandibular body, while 3 cases were in the angle of the mandible. Lesions located below the mandibular canal were observed in 29 cases, while lesions involving the mandibular canal were present in 3 cases. Erosion of the mandibular lingual cortical bone was observed in 11 cases (34.4%), while 21 cases (65.6%) showed no erosion on panoramic images. Among the total of 14 cases (43.8%) where the cortical bone on the affected side was invaded, the average residual cortical bone thickness was 1.1 mm.ConclusionSMBC is a benign lesion primarily found in the mandibular angle and posterior body of the mandible. In most cases, treatment is not necessary, and differentiation from other lesions can be achieved by understanding its clinical characteristics and features on panoramic radiographs and CBCT.

Biomimetic nanoparticles for effective Celastrol delivery to targeted treatment of rheumatoid arthritis through the ROS-NF-κB inflammasome axis

Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA. LEUKO were synthesized using membrane proteins purified from activated J774 macrophage. LEUKO and Cel-loaded LEUKO (Cel@LEUKO) were characterized using dynamic light scattering and transmission electron microscopy. Our results demonstrated that Cel@LEUKO can inhibit the inflammatory response of lipopolysaccharide (LPS) induced mouse monocyte macrophage leukemia cells (RAW264.7 cells) and human rheumatoid arthritis synovial fibroblasts (MH7A) cells through the inhibition of reactive oxygen species (ROS)-NF-κB pathway. In addition, research has shown that LEUKO effectively targets and transports Cel to the inflammatory site of RA, increased drug concentration in affected areas, reduced systemic toxicity of Cel, and reduced clinical symptoms, inflammatory infiltration, bone erosion, and serum inflammatory factors in collagen-induced arthritis (CIA) rats.

Performance of cone-beam computed tomography (CBCT) in comparison to conventional computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone invasion in oral squamous cell cancer (OSCC): a prospective study

BackgroundOral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC.MethodsWe investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction (“0”), cortical bone erosion (“1”), or medullary bone invasion (“2”). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities.ResultsOur results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI.ConclusionOur data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.

A Review of Some the Physiological Effects of Methotrexate on Rheumatoid Arthritis

Rheumatoid arthritis is one of the most prevalent autoimmune diseases at the present time, and it affects both sexes and is characterized by the incidence of women more than men about 1:3. Arthritis causes many negative effects in the various body systems, represented by the lymphatic, respiratory, muscular and blood systems, in addition to its effect on the heart, blood vessels and kidneys. Cytokines have an important role in stimulating the occurrence of rheumatoid arthritis, and these cytokines (IL-1, TNF-α, IL-8) attract inflammatory cells to the synovial membrane due to the erosion of bones and joints. Amethopterin, 4-amino 4-deoxy-N10-methylpteroyl-glutamic acid is a folate antagonist) developed more than 50 years ago in combination with several antifolate therapies used to fight malignant tumors. This review study Further elucidation of the mechanism of methotrexate to treat RA in the patients Methotrexate remains the mainstay of RA treatment and it important to identify the patients in whom the drug is effective and those in which toxicity may be an issue. Genetic and biomarkers may help to stratify patients and possibly shed light on the mechanism for efficacy and for toxicity of methotrexate for RA.

Concomitant Sjögren’s disease as a biomarker for treatment effectiveness in rheumatoid arthritis - results from the Swiss clinical quality management cohort

ObjectiveTo investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren’s disease (SjD).MethodsIn this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders.ResultsWe identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07–1.6]; OMA HR 1.12 [0.91–1.37]; JAKi HR 0.97 [0.62–1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46–0.84]) and JAKi (HR 0.52 [0.28–0.96]).ConclusionRA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi.

Lack of Syndecan-1 promotes the pathogenesis of experimental rheumatoid arthritis.

Syndecan-1 (Sdc-1), a transmembrane heparan sulfate protein, is implicated in several pathophysiological processes including rheumatoid arthritis (RA). The exact role of Syndican-1 in this autoimmune disease is still undetermined. This study explores the involvement level of Sdc-1 in the development of RA in a collagen II-induced arthritis mice model. RA was induced in two mice strains (wild-type BALB/c group and Sdc-1 knockout) by collagen II. Mice underwent regular clinical observations and scoring. After sacrifice, leg biopsies were taken from mice for histological examination, using a variety of stains. In addition, proteins were extracted, and molecular assessment of TNF-α was performed using the western blot technique. In the Sdc-1 knockout group, clinical scoring results showed a significantly more severe experimental RA; histology showed a significant increase in bone erosion, cartilage destruction, inflammation, and less granulated mast cells than the wild-type. In addition, molecular assessment of TNF-α showed more increase in expression in the Sdc-1 knockout models compared to the wild-type. Data suggest that lack of Sdc-1 enhances the inflammatory characteristics in RA. However, more molecular studies and investigations are needed to determine its exact role and possible mechanisms involved.

Interleukin-35 protein inhibits osteoclastogenesis and attenuates collagen-induced arthritis in mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features include synovial inflammation, bone erosion, and joint structural damage. Our previous studies have shown that interleukin (IL)-35 is involved in the pathogenesis of bone loss in RA patients. In this study, we are further evaluating the efficacy of IL-35 on collagen-induced arthritis (CIA) in the mouse model.Male DBA/1J mice (n = 10) were initially immunized, 2 μg/mouse IL-35 was injected intraperitoneally every week for 3 weeks after the establishment of the CIA model. Clinical arthritis, histopathological analysis, and three-dimensional micro-computed tomography (3D micro-CT) were determined after the mice were anesthetized on the 42th day. In vitro, RANKL/M-CSF induced mouse preosteoclasts (RAW264.7 cells line) was subjected to antiarthritis mechanism study in the presence of IL-35.The results of clinical arthritis, histopathological analysis, and 3D micro-CT, the expression of RANK/RANKL/OPG axis, inflammatory cytokines, and osteoclastogenesis-related makers demonstrated decreasing severity of synovitis and bone destruction in the ankle joints after IL-35 treatment. Furthermore, IL-35 attenuated inflammatory cytokine production and the expression of osteoclastogenesis-related makers in a mouse preosteoclasts cell line RAW264.7. The osteoclastogenesis-related makers were significantly reduced in IL-35 treated RAW264.7 cells line after blockage with the JAK/STAT1 signaling pathway. These results demonstrated that IL-35 protein could inhibits osteoclastogenesis and attenuates CIA in mice.We concluded that IL-35 can exhibit anti-osteoclastogenesis effects by reducing the expression of inflammatory cytokines and osteoclastogenesis-related makers, thus alleviating bone destruction in the ankle joint and could be a potential therapeutic target for RA.

Pott's puffy tumor of the upper eyelid misdiagnosed as simple abscess: a case report and literature review.

A 76-year-old woman, initially thought to have a simple abscess on her right upper eyelid, presented to our department of plastic and reconstructive surgery. Enhanced three-dimensional facial computed tomography (CT) revealed an abscess on the right upper lid, with a pyomucocele present in the right frontal sinus, accompanied by bone erosion in the superior wall of the right orbit. Based on the results of the CT scan, we diagnosed an atypical Pott's puffy tumor (PPT) with an abscess on the upper lid originating from the frontal sinusitis. First, surgical incision and drainage were performed in our department, and a percutaneous vacuum drain was placed. To provide a more definitive treatment, endoscopic sinus surgery (ESS) was subsequently performed by otorhinolaryngologists. The patient was discharged without any complications 5 days after ESS. At a 1-year follow-up, no recurrence or notable neurological symptoms were observed. In the case we observed, the patient presented with an upper eyelid abscess and cellulitis, indicating possible orbital involvement. For such patients, a CT scan is necessary. Given the possibility of PPT, it is critical to perform a comprehensive differential diagnosis rather than defaulting to a straightforward approach involving abscess treatment.

Nlrp3 inflammasome drives regulatory T cell depletion to accelerate periapical bone erosion.

Apical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome-mediated immune response on the apical periodontitis was investigated. RNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through invitro experiments. Invivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis. Our findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune-related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL-dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF-κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3-deficient and wild-type Treg cells effectively prevent the bone erosion during apical periodontitis. Together, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion.

Clinical characteristics and risk factors associated with bone erosion in patients with tophi

IntroductionIf a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi.MethodsA total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion.ResultsCompared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion.ConclusionsTophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.

Apoptotic extracellular vesicles restore homeostasis of the articular microenvironment for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a severe autoimmune disease with symptoms including synovial inflammation, cartilage erosion, and bone loss in RA lesions, which eventually lead to joint deformity and function loss. Most current treatments fail to achieve satisfying therapeutic outcomes with some adverse effects. Extracellular vesicles derived from apoptotic cells (apoEVs) have emerged as important mediators in intercellular communication regulating diverse physiological and pathological processes. In this study, we investigated the therapeutic efficacy of macrophage-derived and osteoclast-derived apoEVs (Mφ-apoEVs and OC-apoEVs) on RA. The in vitro results showed that both Mφ-apoEVs and OC-apoEVs induced macrophage repolarization toward the anti-inflammatory M2 phenotype, promoted chondrocyte functions and chondrogenesis, and inhibited osteoclast formation and maturation. In addition, OC-apoEVs promoted osteogenic differentiation. The in vivo study on the CIA mouse model further demonstrated that apoEVs could couple various functions and exert synergistic effects on the joint with RA, as evidenced by the regression of synovial inflammation, the reversal of cartilage damage and bone erosion, and the preservation of joint structure. These findings demonstrated that Mφ-apoEVs and OC-apoEVs contributed to restoring the homeostasis of the overall microenvironment in the RA joint and highlighted their potential application as a promising alternative to treat RA.

Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT

ObjectiveMonosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored. MethodsPatients received pegloticase (8mg every 2weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (VMSU)<0.5cm3 were excluded to minimize artifact contributions. VMSU and bone-erosion remodeling were assessed. ResultsEight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week 52, VMSU had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation. ConclusionRapid VMSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, VMSU reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT. Clinical trial registrationNCT03994731.

Foot involvement in psoriatic arthritis: Prevalence, clinical and radiological features

BackgroundThe purpose of this study was to evaluate the prevalence of foot involvement in psoriatic arthritis and to describe its different clinical and radiological features. Patients and MethodsWe conducted a cross sectional study including 40 patients with psoriatic arthritis over a period of 12 months. Anamnesis, clinical examination of feet, podoscopic examination, X-rays of feet and heels, and ultrasound in B mode and power Doppler mode were done for each patient. ResultsFoot involvement was found in 95% of cases. It was symptomatic in 70% and inaugural of the disease in 20% of cases. The hindfoot and the forefoot were the sites most affected (77.5% and 47.5% respectively). The involvement of the midfoot was rarer (25%). Dactylitis was found in 17.5% and deformities of forefoot were found in 22.5% of cases. Antalgic gait was noted in 17.5% and static disorders of foot at podoscopic examination were identified in 35% of cases. Feet dermatological manifestations were found in 45% of cases. Diagnosis of different rheumatological manifestations was based on clinical findings and caracteristic radiological images on X-rays. We demonstrate he sensitivity of ultrasound in the detection and the diagnosis of different foot lesions including enthesitis, synovitis and tenosynovitis, dactylitis, bone erosions and psoriatic nail dystrophy.

Correlation of US-7 and US-9 Scores with Disease Activity Score using 28 Joint Counts (DAS28) in Patients with Rheumatoid Arthritis.

The attentive management of rheumatoid arthritis (RA) has attracted particular attention. The German 7-joint Ultrasound (US-7) is the first scoring system that combines bone erosions and soft tissue lesions in a single composite scoring system. This study aimed to assess the correlation between US-7 and Disease Activity Score Using 28 Joint Counts (DAS28) in clinically active RA patients. The efficacy of a novel ultrasound score-based system, the US-9 score (joints assessed with US-7 plus knees), was also compared with the standard US-7 score. All the RA patients referred to the outpatient rheumatology clinic of Ghaem Hospital, Mashhad, Iran, during 2019-2020 were included. 28 joints were clinically examined to calculate DAS28. Nine joints were assessed comprising the German US-7 plus knees using grayscale ultrasonography (GSUS) and power Doppler ultrasonography (PDUS). Retrieved data were analyzed by SPSS software, version 22. The Spearman Correlation test was used to find the correlation between DAS28 and ultrasonographic findings. The statistical significance level was set at P<0.05. This study was composed of thirty-five RA patients with a mean age of 49.1±12.0 years. US-7 synovitis scores in GSUS and PDUS were significantly correlated with DAS28 (P=0.02, r=0.38 and P=0.003, r=0.48, respectively). US-9 synovitis scores in GSUS and PDUS were also significantly correlated with DAS28 (P=0.003, r=0.49 and P=0.006, r=0.45, respectively). The synovitis score measured by GSUS was significantly correlated with the GSUS knee synovial score (P=0.01, r=0.42). Ultrasound assessment of large joints such as knees can be an effective approach to determining RA severity. However, it can be proposed that adding more involved joints into the sonographic assessment does not necessarily provide a better clinical correlation.

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, pannus formation and bone erosion. Various immune cells, including macrophages, are involved in RA pathogenesis. The heterogeneity and plasticity of macrophages render them pivotal regulators of both the induction and resolution of the inflammatory response. Predominantly, two different phenotypes of macrophages have been identified: classically activated M1 macrophages exacerbate inflammation via the production of cytokines, chemokines and other inflammatory mediators, while alternatively activated M2 macrophages inhibit inflammation and facilitate tissue repair. An imbalance in the M1/M2 macrophage ratio is critical during the initiation and progression of RA. Macrophage polarization is modulated by various transcription factors, epigenetic elements and metabolic reprogramming. Curcumin, an active component of turmeric, exhibits potent immunomodulatory effects and is administered in the treatment of multiple autoimmune diseases, including RA. The regulation of macrophage polarization and subsequent cytokine production as well as macrophage migration is involved in the mechanisms underlying the therapeutic effect of curcumin on RA. In this review, we summarize the underlying mechanisms by which curcumin modulates macrophage function and polarization in the context of RA to provide evidence for the clinical application of curcumin in RA treatment.

Osteoimmunology: The Crosstalk between T Cells, B Cells, and Osteoclasts in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an ongoing inflammatory condition that affects the joints and can lead to severe damage to cartilage and bones, resulting in significant disability. This condition occurs when the immune system becomes overactive, causing osteoclasts, cells responsible for breaking down bone, to become more active than necessary, leading to bone breakdown. RA disrupts the equilibrium between osteoclasts and osteoblasts, resulting in serious complications such as localized bone erosion, weakened bones surrounding the joints, and even widespread osteoporosis. Antibodies against the receptor activator of nuclear factor-κB ligand (RANKL), a crucial stimulator of osteoclast differentiation, have shown great effectiveness both in laboratory settings and actual patient cases. Researchers are increasingly focusing on osteoclasts as significant contributors to bone erosion in RA. Given that RA involves an overactive immune system, T cells and B cells play a pivotal role by intensifying the immune response. The imbalance between Th17 cells and Treg cells, premature aging of T cells, and excessive production of antibodies by B cells not only exacerbate inflammation but also accelerate bone destruction. Understanding the connection between the immune system and osteoclasts is crucial for comprehending the impact of RA on bone health. By delving into the immune mechanisms that lead to joint damage, exploring the interactions between the immune system and osteoclasts, and investigating new biomarkers for RA, we can significantly improve early diagnosis, treatment, and prognosis of this condition.

Rates of subacromial notching are low following reverse shoulder arthroplasty with a 135° inlay humeral component and a lateralized glenoid

BackgroundLateralization in reverse shoulder arthroplasty (RSA) decreases bony impingement and improves rotational range of motion, but has been theorized to increase the risk of subacromial notching (SaN). The purpose of this study was to evaluate the presence of SaN following RSA and its relationship with lateralization with a 135° inlay humeral component. The secondary purpose was to assess the association of SaN with functional outcomes. MethodsA retrospective review was performed from a multicenter prospectively collected database on patients who underwent primary RSA from 2015-2021. All RSAs were performed with a 135° inlay humeral component. SaN was defined as bony erosion with sclerotic margins on the undersurface of the acromion on final follow-up radiographs not present preoperatively. Postoperative implant positioning (inclination, distalization, and lateralization) were evaluated on minimum 1 year postoperative radiographs. Regression analyses were performed on implant and clinical variables to assess for risk factors. A separate analysis was performed to determine the association of SaN with clinical outcomes. ResultsSaN was identified in 13 out of 442 shoulders (2.9%). Age, sex, body mass index, smoking status, diabetes mellitus, arm dominance had no relationship with SaN. Neither glenoid sided lateralization nor humeral offset were associated with SaN risk. Other implant characteristics such as distalization, glenosphere size, and postoperative inclination did not influence SaN risk. The presence of SaN did not affect patient reported outcomes (PROs) (ASES: p = 0.357, VAS: p = 0.210) or range of motion. ConclusionThe rate of SaN is low and not associated with glenoid or humeral prosthetic lateralization when using a 135° inlay humeral component. When SaN occurs, it is not associated with functional outcomes or range of motion at short term follow-up.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice

Background: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. Purpose: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. Study Design: Controlled laboratory study. Methods: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro−computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. Results: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. Conclusion: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. Clinical Relevance: TXA might be beneficial in patients with posttraumatic OA of the knee.

Time- and Concentration-Dependent Stimulation of Oxidative Stress in Chondrocytes by Intracellular Soluble Urate.

Gout could result in irreversible bone erosion, and chondrocyte might be involved in the process. Increased soluble urate is the early stage of gout and is strongly oxidative. To explore the effect of intracellular urate on the oxidative status of chondrocytes. A chondrocyte model was used. Serial concentrations of exogenous urate were incubated with chondrocytes for increasing amounts of time. Reactive oxygen species (ROS), oxidant, and anti-oxidant molecules were measured with biochemical assays, rt-PCR, and western blot. A urate transport inhibitor and oxidative inhibitors were used to confirm the effect of exogenous urate. All concentrations of exogenous urate stimulated the production of ROS in a time- and concentration-dependent manner, as well as oxidant molecules, including hydrogen peroxide (H2O2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nitric oxide (NO) inducible nitric oxide synthase (iNOS), and these effects, could be inhibited by oxidant inhibitors. However, anti-oxidant molecules, including acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), ataxia-telangiectasia mutated (ATM), heme oxygenase-1 (HO-1), and the transcription factor nuclear factor erythroid 2 (NF-E2)-related (Nrf2), was decreased by high concentrations of exogenous urate after prolonged incubation, but not by low to medium concentrations of exogenous urate. By inhibiting soluble urate trafficking, benzbromarone significantly suppressed the effect of urate stimulus on the oxidant and anti-oxidant molecules. Intracellular soluble urate could regulate chondrocyte redox balance in a time and concentration-dependent manner, and would be a target for regulating and protecting chondrocyte function in the early gout stage.

Transdermal delivery and exploration of preclinical anti-rheumatoid efficacy of pirfenidone embedded nanoemulgel in adjuvant-induced rat model

To avoid adverse effects associated with non-site-specific delivery and target major signaling pathways responsible for the inflammation in rheumatoid arthritis, the current study aims to formulate and evaluate the transdermally administered potential of pirfenidone nanoemulgel in rheumatoid arthritis. The pirfenidone was initially loaded into nanoemulsion by spontaneous nanoemulsification method. The optimized pirfenidone-loaded nanoemulsion diluted with distilled water has shown a droplet size of 9.46 ± 0.01 nm with uniform size distribution evaluated by photon correlation spectroscopy. The optimized pirfenidone nanoemulsion was converted into gel formulation by adding SEPINEO™ P600 gel base with the help of magnetic stirring. The optimized pirfenidone-loaded nanoemulgel has shown a viscosity of 769 ± 05 Pa s with an antigravity nature. Ex vivo permeation study of pirfenidone nanoemulgel in BALB/c mice skin resulted in 1.7 times higher permeation of pirfenidone than free pirfenidone loaded gel. The preclinical efficacy of pirfenidone-loaded nanoemulgel has shown promising results in the rheumatoid arthritis-induced rat model. The right hind paw thickness (##p < 0.01) and arthritis severity score (####p < 0.0001) in pirfenidone nanoemulgel treated group resulted in significant reduction than negative control on 25th day of study. The spleen (****p < 0.0001) and liver indices (**p < 0.01) in rat group treated with pirfenidone nanoemulgel were found to be significantly reduced than negative control. The serum levels of IL-1β (***p < 0.001) and IL-6 (**p < 0.01) were significantly decreased in the pirfenidone nanoemulgel treated group compared to negative control evaluated using enzyme linked immunosorbent assay. The radiographic images of pirfenidone nanoemulgel treated group showed reduction in swelling of soft tissue and bone erosion than negative control. The examination of the hind paw showed improved condition of paw joint with increased synovial space, reduction in the cellular infiltrates and decrease in the swelling of the joints in the pirfenidone nanoemulgel treated group.