Bone Erosion Score Research Articles

Joint Damage and Low Lean Body Mass in a Cohort of Peruvian Patients With Rheumatoid Arthritis.

To determine the association between radiologic joint damage (JD) and a lower lean body mass (LBM) in rheumatoid arthritis (RA) patients. A cross-sectional study from a single center established RA cohort. JD and appendicular LBM (arms and legs) were measured with the Sharp/van der Heijde (SvdH) score and dual x-ray absorptiometry expressed as kg/m 2 , respectively. A univariable analysis was used to determine the association between JD an LBM; then, a multivariable regression model was performed to evaluate the persistence of this association, adjusted by age, gender, disease duration, socioeconomic status (by the Graffar method), tobacco use, anticitrullinated protein antibody levels, Disease Activity Score in 28 joints for RA with erythrocyte sedimentation rate, glucocorticoid use (as prednisone equivalent), disease-modifying antirheumatic drug use, body mass index, and disability (by the multidimensional Health Assessment Questionnaire). Two hundred forty-seven patients were included; the average (SD) age was 63.0 (12.8) years, disease duration 20 (15.00) years, the total SvdH was 66 (86.75), and the aLBM was 13.6 (3.82) kg/m 2 . In the univariable analysis, a lower appendicular LBM was associated with higher SvdH score on the female population, in terms of the total ( B = -8.6, p < 0.01), bone erosion (-4.4, p < 0.01), and joint space narrowing (-4.2, p < 0.01) scores; this correlation remained in the multivariable analysis in terms of total SvdH ( B = -9.5, p < 0.01), bone erosion (-5.2, p < 0.01), and joint space narrowing (-4.3, p < 0.01). A lower LBM in female patients was associated with more severe JD independently of other variables examined. Strategies aimed at preserving LBM could have a favorable impact on the course of disease.

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.

MRI ankle in juvenile idiopathic arthritis and its comparison with clinical disease activity scores

Objectives: Juvenile idiopathic arthritis (JIA) is a common cause of morbidity and consequent disability among youth up to 16 years of age. Our study aims to image the ankle joints of JIA patients and correlate the findings with the clinical disease activity scores. Juvenile Arthritis Disease Activity Score (JADAS-27) is used by pediatricians to assess disease activity in JIA patients. There are four factors that determine this score – Global assessment of disease activity by the physician as well as patient/parent, joint count with active disease, and erythrocyte sedimentation rate (ESR). However, these clinical scores are dependent on the clinician’s experience and observation and, therefore, subjective. Material and Methods: Thirty patients of either sex with a clinical diagnosis of JIA as per the International League of Association for Rheumatology definition with clinically involved ankle joints were included in the study. Chronic arthritis due to other causes, such as infection, trauma, and so on, was excluded. All clinically diagnosed cases of JIA were subjected to magnetic resonance imaging (MRI) evaluation on Siemens Skyra 3 Tesla High-Resolution MR system using a dedicated coil for the ankle joint. Six sub-joints for each patient are evaluated, namely - The tibiotalar joint, subtalar joint, calcaneocuboid joint, calcaneonavicular joint, naviculocuneiform joint, and tarsometatarsal joint. Image analysis and scoring shall be done for each patient at each joint as per the Juvenile Arthritis MRI SCORE, consisting of the following parameters-synovial hypertrophy score, cartilage lesion score, bone erosion score, and bone marrow change score. Each of these scores is calculated individually based on the percentage of involved bone volume. All individual scores were summed to get the total MRI Score. The data collected were then statistically analyzed. Results: A positive correlation was sought between the JADAS-27 score and the total MRI score with the P-value being 0.03. A positive correlation was also found between the total MRI score and the ESR value of the patient (P - 0.02). Conclusion: MRI findings can be a potential marker of disease activity in JIA patients and these findings could also predict the prognosis accurately in these patients. The findings are objective and comparable to the aforementioned clinical scores.

Ultrasonographic study of hand joints erosions in rheumatoid arthritis: Relation to clinical characteristics, disease activity and functional status

BackgroundRheumatoid arthritis (RA) is a commonly diagnosed chronic inflammatory arthritis. Bone erosion can occur early during RA and is considered as an important predictor of a severe clinical course. Aim of the workTo assess ultrasound-detected bone erosions in RA patients and establish their associations with clinical and laboratory variables. Patients and methodsThis study included sixty RA patients. The dorsal and volar joint aspects of the wrist (midcarpal and radiocarpal joints), the first to the fifth metacarpophalangeal (MCP) and proximal interphalangeal joints were scanned in the long and short axes for synovial hypertrophy, tenosynovitis, and erosions. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) were performed. The disease activity score (DAS28) and health assessment questionnaire (HAQ) was evaluated ResultsThe mean age of the patients was 43 ± 11.04 years with median disease duration of 5 (0.1–20) years and there were 57 females. Forty-one patients had bone erosions and 19 did not. Erosions were most frequently found in the MCP joints (48.3 % of examined patients). There was no significant difference between the two groups regarding age (p = 0.36), gender (p = 1), RF (p = 0.4), and anti-CCP (p = 0.6). The bone erosion scores significantly correlated with swollen joint count (p = 0.001), tender joint count (p = 0.018), patient global health (p = 0.024), DAS28 (p = 0.003), HAQ (p = 0.032), ESR (p = 0.005), presence of synovitis (p = 0.005), and synovitis score (p < 0.001). ConclusionsThe US-detected bone erosions are predominant in RA, most frequently at the MCP joints, and are associated with disease activity, inflammatory markers, and synovitis.

The Role of Ultrasound Semi-Quantitative Scoring in the Diagnosis and Assessment of Gout and Hyperuricemia.

To develop an ultrasound semi-quantitative scoring system for the diagnosis and evaluation of gout and hyperuricemia. This study included 348 male patients: 81 patients with asymptomatic hyperuricemia, 182 patients with gout, and 85 patients with other arthritis. Clinical data were collected, ultrasound was detected, gout activity score was calculated to assess disease activity, and statistical analysis was performed. Monosodium urate crystal deposition and subclinical arthritis were detected in 17 patients with asymptomatic hyperuricemia, with lesions concentrated in the metatarsophalangeal joint, ankle and peroneus-longus and brevis at rate of 91.8%. Gout was significantly higher than non-gouty arthritis in crystal scores (sum scores of double contour, aggregates, and tophi), but not in inflammation scores (sum scores of synovial hypertrophy, power Doppler [PD] activity, and tenosynovitis) and bone erosion. The optimal cut-off score for the diagnosis of gout by the crystal score was 2. The sensitivity, specificity, and AUC were 95.4%, 97.1%, and .965, respectively. Gout flare had higher inflammation scores than intercritical gout, while bone erosion scores were lower than intercritical gout. The active gout patients had higher ultrasound scores of tophi, bone erosion, and PD activity than the remission group (P < .001). The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the identification with high disease activity gout by ultrasound semi-quantitative composite score were 76.2%, 84.2%, and .812, respectively. Ultrasound helps early identification of patients at risk in asymptomatic hyperuricemia. Ultrasound semi-quantitative scoring allows for more objective and accurate assessment of gout lesions, correlates with disease activity, and helps in the diagnosis and assessment of gout.

Detailed analysis of the association between urate deposition and bone erosion in gout: a dual-energy computed tomography study.

This study aimed to analyze the effect of urate deposition (UD) on bone erosion and examine the association between the volume of monosodium urate (MSU) crystals and an improved bone erosion score method, as measured in the metatarsophalangeal (MTP) joints of patients with gout. Fifty-six patients diagnosed with gout using the 2015 European League Against Rheumatism and American College of Rheumatology criteria were enrolled. MSU crystals volume at each MTP joint was measured using dual-energy computed tomography (DECT) images. The degree of bone erosion was evaluated with the modified Sharp/van der Heijde (SvdH) erosion scoring system based on CT images. Differences in clinical features between patients with (UD group) and without (non-UD group) UD were assessed, and the correlation between erosion scores and urate crystal volume was analyzed. The UD and non-UD groups comprised 30 and 26 patients, respectively. Among the 560 MTP joints assessed, 80 showed MSU crystal deposition, and 108 showed bone erosion. Bone erosion occurred in both groups but was significantly less severe in the non-UD group (p <0.001). Both groups had equivalent levels of serum uric acid (p=0.200). Symptom duration was significantly longer in the UD group (p=0.009). The UD group also had a higher rate of kidney stones (p=0.023). The volume of MSU crystals was strongly and positively associated with the degree of bone erosion (r=0.714, p <0.001). This study found that patients with UD show significant increased bone erosion than those without UD. The volume of MSU crystals is associated with the improved SvdH erosion score based on CT images, regardless of serum uric acid level, demonstrating the potential of combining DECT and serum uric acid measurements in helping optimize the management of patients with gout.

A Role for Mast Cell-Mediated Antibodies in the Formation of Cholesteatoma and Cholesteatoma-Induced Bone Erosion.

The study aimed to evaluate the effects and relationships between mast cells in the matrix, mast cell enzymes tryptase and chymase, epithelial proliferation, microvascular density, and bone destruction in cholesteatoma. Thirty-five biopsies diagnosed with cholesteatoma and seven healthy skin tissues taken from the retro-auricular region for control were evaluated. Immunohistochemical studies were performed with CD117, CD34, Ki-67, chymase, and tryptase antibodies, in a single session for all cases and the control group. The relationship between erosion size and antibody load was determined. The mean cholesteatoma epithelium Ki-67 was higher than the control group (p < 0.001). CD117-positive mast cells, chymase-positive mast cells, tryptase-positive mast cells, and microvessel density were significantly higher in the cholesteatoma matrix compared to the control group (p < 0.002, p < 0.001, p < 0.005). In the group with bone erosion scores of two and above, immunohistochemical markers tended to be higher. A positive correlation was found between CD117 and chymase, tryptase, and microvessel density; between tryptase, chymase, and microvessel density; and between chymase and microvessel density. CD117-positive mast cells and chymase-positive mast cells stimulate angiogenesis, increase the epithelium's proliferative capacity in the cholesteatoma matrix, and form cholesteatoma. The increased proliferation of cholesteatoma epithelium and increased vascular density in the matrix exacerbate bone erosion.

Quantification of pre-existing radiographic damage and its relationship with joint activity and long-term clinical outcomes with secukinumab therapy in patients with psoriatic arthritis

BackgroundPsoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab.MethodsPooled data (N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed. The association between joint activity (tenderness, swelling) and vdH-mTSS was assessed at the overall patient-level and individual joint tender, swollen scores (yes/no) and RD joint JSN and bone erosion scores at the individual joint-level. Treatment response was assessed using SJC/TJC at weeks 16 and 52 and the proportion of patients achieving minimal disease activity (MDA) over all assessments within 1 year from FUTURE 5 alone.ResultsA substantial prevalence of pre-existing RD with higher prevalence of erosion than JSN was observed (86% and 60% of patients had positive erosion and JSN scores, respectively); higher RD prevalence was associated with longer time since PsA diagnosis. Joint activity was weakly associated with RD at baseline at the patient-level (Pearson’s coefficients: range 0.12–0.18), but strongly associated at the individual joint-level, with a higher probability of tender/swollen joints to associate with higher JSN/erosion scores: all 42 analysed joints showed statistical significance at the 0.05 level (unadjusted) for the relationship between joint tenderness (yes/no) and its JSN score, all but one for tenderness and bone erosion scores, and all but 2 for swollen and JSN scores and for swollen and bone erosion score. Secukinumab (150/300 mg), reduced TJC and SJC across all values of baseline erosion and JSN scores at weeks 16 and 52. Patients with higher levels of RD were less likely to achieve zero tender/zero swollen joint status and had lower chance of achieving MDA.ConclusionsPsA patients showed substantial prevalence of RD at baseline that correlated with time since diagnosis, but patient’s individual joint activity was strongly associated with pre-existing RD at those joints. Patients with the highest RD at baseline had a reduced likelihood of achieving zero joint count status.

High-frequency ultrasound in patients with seronegative rheumatoid arthritis.

This study aimed to investigate the value of high-frequency ultrasound (HFUS) in differentiation of the seronegative rheumatoid arthritis (SNRA) and osteoarthritis (OA) and in the diagnosis of SNRA. 83 patients diagnosed with SNRA (SNRA group) and 40 diagnosed with OA (OA group) who received HFUS were retrospectively analyzed. The grayscale (GS) scores, power Doppler (PD) scores, and bone erosion (BE)scores were recorded, and added up to calculate the total scores of US variables. The correlations of the total scores of US variables with the 28-joint diseaseactivityscore (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were analyzed. The diagnostic efficacy of the total scores of US variables for SNRA was assessed. In the SNRA group, the detection rate of abnormal US findings in the joints and tendons by GS and PD as well as BE was higher than those in the OA group. There were significant differences between the two groups in GS scores and PD scores of joints and tendons, and BE scores of joints (P < 0.05). In the SNRA group, the total scores of most US variables were positively correlated with CRP, ESR, and DAS28 (P < 0.05), while such correlations were not observed in the OA group (P > 0.05). Among different US variables, the diagnostic value of total PD scores of the joints was the highest for SNRA. HFUS could be used to differentiate SNRA from OA and make a diagnosis of SNRA based on joint and tendon synovial sheath assessment.

Intensive Serum Urate Lowering With Oral Urate-Lowering Therapy for Erosive Gout: A Randomized Double-Blind Controlled Trial.

To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups. Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.

Distribution of bony erosions in feet and performance of two bone erosion scores: A dual-energy computed tomography study of 61 patients with gout.

ObjectivesTo assess the distribution of bone erosions and two erosion scores in the feet of patients with gout and analyze the association between erosion scores and monosodium urate (MSU) crystal deposition using dual-energy computed tomography (DECT).Materials and methodsWe included all patients who underwent DECT of both feet between 2016 and 2019 in our radiology department, with positive detection of MSU deposits. Data on sex, age, treatment, serum urate, and DECT urate volumes were obtained. CT images were analyzed to score bone erosions in 31 sites per foot by using the semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring (RAMRIS) system and the Dalbeth-simplified score. Reproducibility for the two scores was calculated with intraclass correlation coefficients (ICCs). Correlations between clinical features, erosion scores and urate crystal volume were analyzed by the Spearman correlation coefficient (r).ResultsWe studied 61 patients (mean age 62.0 years); 3,751 bones were scored. The first metatarsophalangeal joint and the midfoot were the most involved in terms of frequency and severity of bone erosions. The distribution of bone erosions was not asymmetrical. The intra- and inter-observer reproducibility was similar for the RAMRIS and Dalbeth-simplified scores (ICC 0.93 vs 0.94 and 0.96 vs 0.90). DECT urate volume was significantly correlated with each of the two erosion scores (r = 0.58–0.63, p < 0.001). There was a high correlation between the two scores (r = 0.96, p < 0.001).ConclusionsDECT demonstrates that foot erosions are not asymmetric in distribution and predominate at the first ray and midfoot. The two erosion scores are significantly correlated with DECT urate volume. An almost perfect correlation between the RAMRIS and Dalbeth-simplified scores is observed.

Denosumab did not improve computerized tomography erosion scores when added to intensive urate-lowering therapy in gout: Results from a pilot randomized controlled trial

Background/PurposeDisordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion. MethodsOpen-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate ≤5 mg/dL or 300 µmol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function. ResultsAlthough serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone). ConclusionsIn this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion.

Filgotinib decreases both vertebral body and posterolateral spine inflammation in ankylosing spondylitis: results from the TORTUGA trial.

ObjectivesTo assess the effects of filgotinib on inflammatory and structural changes at various spinal locations, based on MRI measures in patients with active AS in the TORTUGA trial.MethodsIn the TORTUGA trial, patients with AS received filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, spine MRIs were evaluated using the Canada–Denmark (CANDEN) MRI scoring system to assess changes from baseline to week 12 in total spine and subscores for inflammation, fat, erosion and new bone formation (NBF) at various anatomical locations. Correlations were assessed between CANDEN inflammation and clinical outcomes and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores and between baseline CANDEN NBF and baseline BASFI and BASMI scores.ResultsMRIs from 47 filgotinib- and 41 placebo-treated patients were evaluated. There were significantly larger reductions with filgotinib vs placebo in total spine inflammation score and most inflammation subscores, including posterolateral elements (costovertebral joints, transverse/spinous processes, soft tissues), facet joints and vertebral bodies. No significant differences were observed for corner or non-corner vertebral body inflammation subscores, spine fat lesion, bone erosion or NBF scores. In the filgotinib group, the change from baseline in the total inflammation score correlated positively with the SPARCC spine score. Baseline NBF scores correlated with baseline BASMI but not BASFI scores.ConclusionsCompared with placebo, filgotinib treatment was associated with significant reductions in MRI measures of spinal inflammation, including in vertebral bodies, facet joints and posterolateral elements.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov), NCT03117270.

Anti-Carbamylated LL37 Antibodies Promote Pathogenic Bone Resorption in Rheumatoid Arthritis.

ObjectiveAntibodies against carbamylated proteins (anti-CarP) are associated with poor prognosis and the development of bone erosions in rheumatoid arthritis (RA). RA neutrophils externalize modified autoantigens through the formation of neutrophil extracellular traps (NETs). Increased levels of the cathelicidin LL37 have been documented in the synovium of RA patients, but the cellular source remains unclear. We sought to determine if post-translational modifications of LL37, specifically carbamylation, occur during NET formation, enhance this protein’s autoantigenicity, and contribute to drive bone erosion in the synovial joint.MethodsELISA and Western blot analyses were used to identify carbamylated LL37 (carLL37) in biological samples. Anti-carLL37 antibodies were measured in the serum of HLA-DRB1*04:01 transgenic mice and in human RA synovial fluid.ResultsElevated levels of carLL37 were found in plasma and synovial fluid from RA patients, compared to healthy controls. RA NETs release carLL37 and fibroblast-like synoviocytes (FLS) internalized NET-bound carLL37 and loaded it into their MHCII compartment. HLA-DRB1*04:01 transgenic mice immunized with FLS containing NETs developed autoantibodies against carLL37. Anti-carLL37 antibodies were present in RA sera and synovial fluid and they correlated with radiologic bone erosion scores of the hands and feet in RA patients. CarLL37-IgG immune complexes enhanced the ability of monocytes to differentiate into osteoclasts and potentiated osteoclast-mediated extracellular matrix resorption.ConclusionsNETs are a source of carLL37 leading to induction of anti-carbamylated autoantibody responses. Furthermore, carLL37-IgG immune complexes may be implicated in the bone damage characteristic of RA. These results support that dysregulated NET formation has pathogenic roles in RA.

Predictive role of ultrasound remission for progressive ultrasonography-detected structural damage in patients with rheumatoid arthritis

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. However, there have been no studies that explored the different time...

Impact of denosumab discontinuation on changes in bone mineral density and bone erosion in rheumatoid arthritis patients.

This study investigated changes in bone mineral density (BMD) and erosion after denosumab discontinuation in rheumatoid arthritis (RA) patients without osteoporosis who participated in the DESIRABLE study. This multicentre observational study consisted of a prediscontinuation visit (date of final assessment in DESIRABLE) and a postdiscontinuation visit (2.5 years after the last administered dose of denosumab). Percentage change in lumbar spine (LS) BMD from baseline was assessed as the primary endpoint. Fifty-nine patients were enrolled. The percentage change in LS BMD decreased to baseline levels at the postdiscontinuation visit. Compared with baseline, C-telopeptide of type I collagen levels increased after denosumab discontinuation but most patients had levels within the reference range. Bone erosion scores were not significantly different between the on-treatment period and after denosumab discontinuation (p = .0666) but there was a numerical increase postdiscontinuation. The progression in bone erosion score was significantly reduced in patients whose disease activity was in remission versus those not in remission (p = .0195). In RA patients without osteoporosis, denosumab discontinuation can be explored while considering patient background factors (disease activity and risk of fracture) and accounting for progression of bone erosion and LS BMD decrease after withdrawal.

The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis: Preliminarily data from single center-based observational study for 24 weeks.

Baricitinib is a Janus kinase (JAK) inhibitor that selectively blocks against JAK1 and JAK2 signaling. This study aimed to determine the effect of baricitinib on disease activity based on musculoskeletal ultrasound in patients with rheumatoid arthritis (RA).A total of 20 patients with RA receiving baricitinib for 24 weeks were assessed. Ultrasound scores of gray scale and power Doppler synovitis, joint effusion, and bone erosion in each patient were assessed between baseline and 24 weeks for 27 affected joints. Disease activity in RA was evaluated using the disease activity score for 28-joint count with erythrocyte sediment rate (DAS28-ESR), simplified disease activity index (SDAI), and clinical disease activity index (CDAI).Treatment with baricitinib for 12 weeks and 24 weeks significantly decreased disease activity composites such as DAS28-ESR, SDAI, and CDAI (P < .001 for all). Treatment with baricitinib for 24 weeks improved ultrasound-detected gray-scale and power Doppler synovitis and joint effusion compared to baseline (P = .002, P = .030, and P = .002, respectively). Bone erosion scores were not different between baseline and 24 weeks (P = .317). There were no differences in ultrasound abnormalities for improvement based on DAS28-ESR. Changes in power Doppler score were significantly associated with changes in DAS28-ESR (β = 0.590, P = .044), but not SDAI and CDAI.This study demonstrates that baricitinib treatment has a favorable effect on ultrasound-detected abnormalities including synovitis and bone erosion in patients with RA.

Differential Expression of Ki-67 and P27 in Cholesteatoma Compared to Skin Tissue Predicts the Prognosis of Adult Acquired Cholesteatoma.

Background: The aim of this study was to compare the differential Ki-67 and p27 staining properties of acquired cholesteatoma in adult patients for prognostic analysis.Methods: Forty-two adult patients with acquired cholesteatoma were enrolled. The cholesteatoma and matched meatal skin tissues of the patients were immunostained with Ki-67 and p27 antibodies. Canal wall down mastoidectomy was performed in all patients. The differential staining properties––positive staining in the cholesteatoma and negative staining in the skin tissue (C+S-), negative staining in the cholesteatoma and positive staining in the skin tissue(C-S+)––were compared for bone erosion scores (BES), stage, and recurrence rates.Results: Isolated findings in the cholesteatoma tissues, without matching with the skin tissues, demonstrated that stage and recurrence rates were not related to findings in the cholesteatoma tissues (P ˃ .05). However, C+S- for Ki-67 and C-S+ for p27 are risk factors for worse prognosis including advanced stage (P < .001 for Ki-67 and P = .008 for p27), BES values (P < .001 for Ki-67 and P = .001 for p27), and recurrence rates (P < .001 for Ki-67 and P = .037 for p27).Conclusion: This is the first paper assessing the cholesteatoma prognosis according to the differential Ki-67 and p27 staining properties of cholesteatoma and healthy skin tissues. Cellular proliferation rate in the cholesteatoma is important but insufficient by itself for predicting the prognosis of cholesteatoma patients. Patients having lower basal levels of cellular proliferation rate and higher cellular activity in the cholesteatoma tissue are prone to worse prognosis with increased stage, recurrence rates, and degree of bone erosion.

Comparative Analysis of Clinical and Imaging Features of Osteomalacia and Spondyloarthritis.

Aim: To compare the clinical and radiological characteristics of osteomalacia and spondyloarthritis/ankylosing spondylitis (SpA/AS) in order to provide a basis for differential diagnosis.Methods: We carried out a retrospective analysis of patients who were diagnosed with osteomalacia at the First Medical Center of 301 Hospital (Beijing, China) from January 2012 to January 2019. The clinical and radiological data of all patients were collected; at the same time, we selected age- and gender-matched patients with SpA/AS for comparison.Results: We enrolled a total of 76 patients, 38 with osteomalacia, and 38 with SpA/AS. The mean ages of the two groups were, respectively 44.62 ± 14.90 years and 44.85 ± 9.76 years (P > 0.05). Of patients with osteomalacia, 65.79% (n = 25) had previously been misdiagnosed with SpA/AS. In the osteomalacia and SpA/AS groups, there were, respectively 31 and 33 patients with low back pain, 22 and 13 patients with peripheral arthralgia, and 13 and 3 patients with heel pain. Alkaline phosphatase (ALP) level was significantly higher in the osteomalacia than in the SpA/AS group (P < 0.05). Serum phosphorus levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and bone mineral density (BMD) were significantly lower in the osteomalacia group than the SpA/AS group (P < 0.05). Twenty-five patients in the osteomalacia group underwent sacroiliac-joint magnetic-resonance imaging (SIJ–MRI); abnormalities were found in 10 of these patients, seven of whom met the definition for positive SIJ–MRI according to 2009 Assessment of SpondyloArthritis international Society (ASAS) criteria. All seven presented with bilateral sacral involvement. Logistic-regression analysis found that the odds ratio (OR) for bone erosion score was 0.551; the higher this score, the lower the possibility of osteomalacia.Conclusion: Clinical and radiological presentations of patients with osteomalacia could highly simulate those of patients with spondyloarthritis; identifying the differences between these two diseases could effectively decrease the misdiagnosis rate.

Yishen-tongbi decoction inhibits excessive activation of B cells by activating the FcγRIIb/Lyn/SHP-1 pathway and attenuates the inflammatory response in CIA rats

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Strong evidence supports that excessive activation of B cells plays a critical role in the pathogenesis of RA. Fc gamma receptor b (FcγRIIb) is the B cell inhibitory receptor and inhibits BCR (B cell receptor) signalling in part by selectively dephosphorylating CD19 which is considered a co-receptor for BCR and is essential for B cell activation. Our previous study demonstrated that a FcγRIIb I232T polymorphism presented a strong genetic link to RA and may lead to the excessive activation of B cells. Therefore, novel therapeutic strategies and drugs that can effectively inhibit the excessive activation of B cells by regulating the FcγRIIb are necessary for the treatment of RA. Therefore, we used Burkitt’s lymphoma ST486 human B cells (lacking endogenous FcγRIIb) transfected with the 232Thr loss-of-function mutant to construct a FcγRIIb mutant cell line (ST486), and we demonstrated that YSTB treatment not only reduced proliferation and promoted apoptosis in ST486 cells but also did so in a dose-dependent manner. Furthermore, the intracellular Ca2+ flux of ST486 cells was decreased after treatment with YSTB, inhibiting the excessive activation of ST486 cells, and these effects correlated with the CD19/FcγRIIb-Lyn-SHP-1 pathways. Our data showed that YSTB treatment inhibited the expression of phosphorylated CD19 and upregulated the protein expression of FcγRIIb, Lyn, and SHP-1. Additionally, the CIA model was established to explore the anti-inflammatory and inhibitory effects of YSTB on bone destruction, and we found that YSTB decreased the paw oedema and arthritis index (AI) in CIA rats. It is worth mentioning that YSTB clearly decreased the AI earlier than methotrexate (MTX) (day 10 vs 16). Moreover, synovial hyperplasia, inflammatory cell infiltration and cartilage surface erosion in CIA rats were noticeably reduced after treatment with YSTB as evidenced by histopathological examination. Finally, we found that YSTB treatment suppressed bone erosion and joint space score (JNS) in CIA rats as evidenced by radiographic assessment. In summary, these data suggest that YSTB has great therapeutic potential for RA treatment.