Skeletal muscle index together with body mass index is associated with secondary osteoporosis in patients with rheumatoid arthritis.

OBJECTIVE: The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). METHODS: The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1-4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI. RESULTS: A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m2, the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ2 = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ2 = 10.951, p = 0.001; 61.1% vs. 13.0%, χ2 = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399-0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805-0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040-0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071-1.125) was the risk factor. CONCLUSION: BMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA.

Association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis in Chinese patients with rheumatoid arthritis.

OBJECTIVES: The study aimed to explore the association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis (GIOP) in Chinese patients with rheumatoid arthritis (RA). METHOD: Skeletal muscle mass, serum 25(OH)D levels, and bone mineral density (BMD) were assessed. RESULTS: The prevalence of OP, sarcopenia, and vitamin D deficiency in RA patients was significantly higher than in controls (all P < 0.001). The percentage of GC use was 56.9%, and the prevalence of GIOP was 38.1% in 480 RA patients. The prevalence of OP in RA patients without sarcopenia was lower than that in RA patients with sarcopenia (P < 0.05). In RA patients with and without GC, the prevalence of OP in patients without sarcopenia was significantly lower than that in patients with sarcopenia (P < 0.001 and P < 0.05). Female sex (OR = 54.737; 95% CI: 7.103-421.809; P < 0.0001), age (OR = 1.078; 95% CI: 1.048-1.110; P < 0.0001), sarcopenia, and vitamin D deficiency (OR = 2.250; 95% CI: 1.246-64.065; P = 0.007) were risk factors for GIOP in RA patients. CONCLUSIONS: GIOP is associated with sarcopenia and vitamin D deficiency and is widespread among Chinese patients with RA. Key points ·Percentage of using GC and the prevalence of OP were all high in Chinese patients with RA. ·GIOP was widely existed in Chinese RA patients, which was associated with sarcoprnia and vitamin D deficiency.

RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

Corrigendum: Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: mendelian randomization study in European and East Asian populations.

[This corrects the article DOI: 10.3389/fonc.2023.1170119.].

Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: Mendelian randomization study in European and East Asian populations.

Objective: Associations between diseases of the musculoskeletal system and connective tissue (MSCTD) and breast cancer (BC) have not been elucidated completely. The purpose of this study was to investigate the associations of MSCTD, rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM), osteoarthritis (OA) of hip or knee, and ankylosing spondylitis (AS) with BC in European populations and East Asian populations using Mendelian randomized (MR) analysis. Methods: The genetic instruments linked to MSCTD, RA, SS, SLE, SSc, DM, PM, OA, and AS were chosen from the EBI database of complete genome-wide association studies (GWAS) summary data and the FinnGen consortium. The associations of genetic variants with BC were extracted from the Breast Cancer Association Consortium (BCAC). Two Sample MR was performed using summary data from GWAS, principally using the inverse variant weighted (IVW) method. Heterogeneity, pleiotropy, and sensitivity analyses were performed to evaluate the robustness of the results by weighted median, MR Egger, simple mode, weighted mode, and leave-one-out analysis. Results: In the European population, causal relationships between RA and BC (OR=1.04, 95%CI: 1.01-1.07, P=0.023), AS and BC (OR=1.21, 95%CI: 1.06-1.36, P=0.013) were confirmed. IVW analysis showed DM (OR=0.98, 95%CI: 0.96-0.99, P=0.026) and PM (OR=0.98, 95%CI: 0.97-0.99, P=0.002) were associated with slightly decreased risks of estrogen receptor (ER)+ BC, and MSCTD was associated with an increased risk of ER- BC (OR=1.85, 95%CI: 1.27-2.44, P=0.039). There was no causal relationship between SLE, SS, SSc, OA, and BC, neither ER+ BC nor ER- BC. However, in the East Asian population, IVW analysis showed that RA (OR=0.94, 95%CI: 0.89-0.99, P=0.0096) and SLE (OR=0.95, 95%CI: 0.92-0.99, P=0.0058) was associated with decreased risks of BC. Conclusions: This study suggests that causal relationships between patients with MSCTD and BC in the European population are different from those in the East Asian population, patients with RA and AS in the European population have an increased risk of BC, patients with MSCTD have increased risk of ER- BC in the European population, while patients with RA and SLE in the East Asian population have decreased risk of BC.

A Real-World Study on the Effect of Imrecoxib for Patients with Axial Spondyloarthritis.

Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have generally been viewed as first-line therapy for axial spondyloarthritis (axSpA). Imrecoxib is a selective COX-2 inhibitor developed independently in China. At present, only one single-center RCT trial has shown that imrecoxib is equally effective as celecoxib in treating axSpA. Based on real-world data, our study aims to explore the efficiency of imrecoxib and TNF inhibitor (TNFi) combined with imrecoxib in treating axSpA. Patients and Methods: A total of 163 patients with axSpA who had more than two follow-up records in 6 months and treated with imrecoxib/celecoxib/TNFi combined with imrecoxib/TNFi combined with celecoxib from the First Affiliated Hospital of Anhui Medical University SpA Real World Database (AHSpA) were selected for analysis of our study. The linear mixed model was used to compare efficacy indexes before and after treatment and between different groups, adjust baseline measurement value and follow-up time. The Kaplan-Meier survival analysis was used to identify the differences in cumulative clinical remission rates between groups with different treatment at the follow-up period. Results: Results showed that after treatment ASDAScrp was slightly improved in imrecoxib group and celecoxib group within 6 months (p < 0.05). CRP, ESR, BASDAI, ASDAScrp, BASFI, occiput to wall distance and finger floor distance all significantly improved in TNFi combined with imrecoxib group and TNFi combined with celecoxib group within 6 months (all p < 0.05). According to the Kaplan-Meier survival curve and Log rank test analysis, the clinical remission rate was not significantly different between different treatment during 24-month follow-up (all p > 0.05). Conclusion: ASDAScrp improved slightly within 6 months after treatment with imrecoxib, and TNFi combined with imrecoxib significantly improved multiple effect indexes in axSpA patients. The efficacy of imrecoxib and celecoxib in the treatment of axSpA is equivalent. Also, they have the same efficacy after being combined with TNFi.

Synergy of sarcopenia and vitamin D deficiency in vertebral osteoporotic fractures in rheumatoid arthritis.

OBJECTIVES: To explore the synergistic effect of vitamin D deficiency and sarcopenia on vertebral osteoporostic fracture (VF) in patients with rheumatoid arthritis (RA). METHODS: A total of 188 patients with RA and 158 control subjects were enrolled. Bone mineral density (BMD) at the total hip, neck of femur, lumbar vertebra 1-4, and skeletal muscle mass was measured by dual energy X-ray absorptiometry (DXA) and biological electrical impedance, respectively. Serum 25(OH)D was tested by electrochemiluminescence. The prevalence of VF and osteoporosis (OP) were compared between RA and controls. The synergism of sarcopenia and vitamin D deficiency on VF in patients with RA was tested by χ2 test and logistic regression. RESULTS: The prevalence of OP at all measured sites and VF in RA patients were all higher than those in controls (P < 0.0001). The incidence of VF in RA either with sarcopenia or with vitamin D deficiency was higher than for those without sarcopenia or without vitamin D deficiency (χ2 = 5.069, P = 0.027, χ2 = 8.822, P = 0.001). Age, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28, health assessment questionnaire (HAQ), Sharp score, and body mass index (BMI) were significantly different between RA with sarcopenia or not (P < 0.05). Logistic regression analysis found that age (OR = 1.095, 95%, CI: 1.044-1.150, P < 0.0001) was a significant risk factor for VF in patients with RA, while high skeletal muscle mass (SMI) (OR = 0.513, 95% CI: 0.327-0.804, P = 0.004) was a protective factor for VF in RA patients. CONCLUSIONS: VF, sarcopenia, and vitamin D deficiency are common in patients with RA. Sarcopenia and vitamin D deficiency may be risk factors for the incidence of VF in RA patients. KEY POINTS: • RA patients had a higher incidence of OP and VF, also a high prevalence of sarcopenia and vitamin D deficiency. • Vitamin D deficiency and sarcopenia may might have a synergistic effect on VF in RA. • Aging and sarcopenia are risk factors for VF in RA patients, and sarcopenia were associated with disease activity and structural damage.

Presence of subclinical inflammation in axial spondyloarthritis patients with NSAID/anti-TNF-α drug-induced clinical remission.

OBJECTIVE: To investigate the rate of subclinical inflammation in patients with axial spondyloarthritis (axSpA) with nonsteroidal anti-inflammatory drug (NSAID)/anti-tumor necrosis factor (TNF)-α drug-induced clinical remission and to explore factors influencing clinical and imaging remission. METHODS: One hundred twenty-five patients with axSpA followed up for at least 6 months were enrolled in this prospective study and randomly divided into two groups. Ninety patients were treated with anti-tumor necrosis factor (TNF)-α or anti-TNF-α combined with nonsteroidal anti-inflammatory drugs (NSAIDs) (anti-TNF-α treatment group), and thirty-five patients were treated with only NSAIDs (non anti-TNF-α treatment group). The improvements in the clinical remission rate, imaging remission rate, and disease parameters before and after the different treatments were compared. Risk factors for clinical and imaging remission were analyzed by multivariate logistic regression analysis. RESULTS: The clinical and imaging remission rate was increased after treatment especially in the anti-TNF-α group (P < 0.001). The remission rate of imaging in the group with clinical remission was higher than that in the group with clinical non-remission (P < 0.05). After treatment, the remission rates of imaging in the clinical remission and non-remission group were significantly higher than those before treatment (P < 0.0001). The results of multivariate logistic regression analysis showed that higher CRP was a risk factor for failure of clinical remission in axSpA (OR = 2.034, 95% CI:1.595 ~ 2.617, P < 0.001), while higher ASDAScrp was a risk factor for failure of imaging remission (OR = 1.306, 95% CI:1.026 ~ 1.688, P < 0.05). Anti-TNF-α treatment was a protective factor for both clinical (OR = 0.234, 95% CI:0.091 ~ 0.605, P < 0.05) and imaging remission (OR = 0.511, 95% CI:0.286 ~ 0.914, P < 0.05). CONCLUSION: Even after regular treatment, some clinical remission patients continued to have evidence of subclinical inflammation. Higher CRP and ASDAScrp are risk factors for clinical and imaging non-remission in axSpA respectively, Continuous NSAID treatment (more than 1 year) can effectively improve clinical and MRI inflammation in patients, but anti-TNF-α treatment is more beneficial for clinical and imaging remission. Key Points • Some patients achieving ASDAScrp remission status continue to have inflammation when assessed with objective imaging techniques. • MRI can sensitively measure bone marrow inflammation and may provide a more accurate assessment of remission. • Controlling inflammation, especially reducing CRP and ASDAScrp levels, is a key factor for achieving clinical and imaging remission in patients with axSpA.

The Potential Regulatory Mechanism of lncRNA 122K13.12 and lncRNA 326C3.7 in Ankylosing Spondylitis.

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609-0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780-0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.

Interactive effect of sarcopenia and falls on vertebral osteoporotic fracture in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) had higher incidences of sarcopenia, falls, osteoporosis, and vertebral osteoporotic fractures (VOPF). Sarcopenia was associated with longer disease duration, higher disease activity, and more severe RA. The interactive effect of sarcopenia and falls was associated with a higher risk of VOPF in patients with RA. PURPOSE: Whether sarcopenia and falls are a risk factor for vertebral fracture in RA patients has not been demonstrated. This study aimed to explore the incidence of vertebral osteoporotic fracture (VOPF) and its relationship with sarcopenia and falls in RA patients. METHODS: A total of 474 RA patients and 156 controls were enrolled in this study. Anteroposterior and lateral X-ray examinations of the vertebral column (T4-L4) were used for the semiquantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. Skeletal muscle mass was measured by direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA method). RESULTS: RA patients had an increased risk of sarcopenia (62.4% vs 9.0%, x2 = 47.478, P < 0.001), falls (30.2% vs 3.2%), osteoporosis (OP) (33.5% vs 12.8%, x2 = 134.276, P < 0.001), and VOPF (20.3% vs 3.8%, x2 = 47.478, P < 0.001) than controls. Patients with sarcopenia were more likely to have VOPF than RA without sarcopenia (24.0% vs 14.0%, x2 = 6.802, P = 0.009). RA with sarcopenia and prior falls had the highest incidences of VOPF (36.7%). Older age (OR = 1.056, P < 0.001, 95% CI 1.030-1.083), falls (OR = 2.043, P = 0.003, 95% CI 1.238-3.371), OP (OR = 1.819, P = 0.034, 95% CI 1.046-3.163), and usage of glucocorticoids (GCs) (OR = 1.862, P = 0.022, 95% CI 1.093-3.172) were risk factors for VOPF in RA patients, while a higher skeletal muscle index (SMI) was a protective factor (OR = 0.754, P = 0.038, 95% CI 0.578-0.984) for VOPF in RA patients. CONCLUSIONS: The interactive effect of sarcopenia and falls is associated with a higher risk of VOPF in patients with RA.

Synergistic effect of sarcopenia and poor balance on osteoporotic vertebral fracture in Chinese patients with rheumatoid arthritis.

OBJECTIVES: This study aimed to investigate the synergistic effect of sarcopenia and poor balance on osteoporotic vertebral fracture (VOPF) in Chinese patients with rheumatoid arthritis (RA). METHODS: A total of 238 RA patients and 158 normal subjects were enrolled in the case-control study. Poor balance capability (Berg balance scale (BBS) score < 40) and sarcopenia (skeletal muscle mass index (SMI) <7.0 (male)/5.7 (female)) between RA patients and normal subjects were compared. Associations of poor balance capability or sarcopenia with disease activity, structural damage, and joint function in different groups were also investigated. RESULTS: The incidence of sarcopenia in RA was 58.4%, significantly higher than that in controls (P<0.0001). Moreover, the percentages of low balance capacity (BBS<40) in RA were 43.7%, which was higher than that in controls (P<0.0001). The prevalence of VOPF in the case group was 19.3%, which was higher than that in the controls (P<0.0001). In the RA group, compared to RA patients without VOPF, RA patients with VOPF had higher percentages of poor balance and sarcopenia (P<0.05). Compared with RA patients without sarcopenia or good balance, RA patients with sarcopenia or poor balance had a higher incidence of VOPF, higher disease activity, severer structural damage, and worse joint function (P<0.05). The incidence of VOPF in patients combined with good balance and non-sarcopenia (4.8%) was significantly lower than that in patients combined with poor balance and sarcopenia (38.2%) (P<0.0001). Logistic regression indicated that higher SMI and higher BBS scores were protective factors for VOPF in RA patients, while age was a risk factor for VOPF in RA patients (P<0.0001). CONCLUSION: Sarcopenia and poor balance are popular in Chinese patients with RA, and they are associated with disease activity and structural damage. There is a synergistic effect of sarcopenia and poor balance on VOPF in RA. Key Points • Sarcopenia and balance capability were popular (about a half) in patients with RA. • Sarcopenia and poor balance had a synergistic effect on VOPF in RA.