Background. Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods. Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results. The RA + osteoporosis group had elevated sRANKL levels ( p = 0.005 ), higher sRANKL/OPG ratio ( p = 0.017 ), decreased DKK-1 ( p = 0.028 ), and lower SOST levels ( p < 0.001 ). Low total hip BMD correlated with high sRANKL ( p = 0.001 ) and sRANKL/OPG ratio ( p = 0.005 ). Total hip and lumbar spine BMD correlated with DKK-1 ( p = 0.009 and p = 0.05 , respectively) and SOST levels ( p < 0.001 and p < 0.001 , respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures ( p = 0.003 and p = 0.003 , respectively) and hip fracture ( p = 0.002 and p = 0.006 , respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture ( p = 0.003 ) and hip fracture ( p = 0.009 ). Conclusion. High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Background To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial.Objective To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis.Methods Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria. Results SLE patients had higher MIF (p=0.02) and adiponectin (p<0.001) than HCs. Patients with renal SLE involvement (n=43) had higher adiponectin (19.0 vs 13.3 µg/mL, p=0.002) and resistin (10.7 vs 8.9 ng/mL, p=0.01) than patients with non-renal SLE (n=153). Proteinuria correlated with high adiponectin (rs=0.19, p<0.009) and resistin (rs=26, p<0.001). MIF (rs=0.27, p=0.04). Resistin correlated with increased creatinine (rs= 0.18, p=0.02). High renal-SLEDAI correlated with adiponectin (rs=0.21, p=0.004). Multiple linear regression showed that elevated adiponectin (p=0.02), younger age (p=0.04) and low MIF (p=0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2=0.41).Conclusions High adiponectin combined with low MIF concentrations interact to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.

Background To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial. Objective To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis. Methods Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria. Results SLE patients had higher MIF (p = 0.02) and adiponectin (p < 0.001) than HCs. Patients with renal SLE involvement (n = 43) had higher adiponectin (19.0 vs 13.3 μg/mL, p = 0.002) and resistin (10.7 vs 8.9 ng/mL, p = 0.01) than patients with non-renal SLE (n = 153). Proteinuria correlated with high adiponectin (rs = 0.19, p < 0.009) and resistin (rs = 0.26, p < 0.001). MIF (rs = 0.27, p = 0.04). Resistin correlated with increased creatinine (rs = 0.18, p = 0.02). High renal-SLEDAI correlated with adiponectin (rs = 0.21, p = 0.004). Multiple linear regression showed that elevated adiponectin (p = 0.02), younger age (p = 0.04) and low MIF (p = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2 = 0.41). Conclusions High adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.

Irisin stimulates osteoblast differentiation increasing bone mass a decreasing in irisin levels might contribute to osteoporotic fractures in inflammatory diseases. To date, there is controverted whether irisin levels are associated with osteoporotic fractures in rheumatoid arthritis (RA). Therefore, we evaluate the association of serum irisin with osteoporotic Vertebral Fractures (VFs) in women with RA.A total of 148 women with RA was included in the study. Clinical characteristics and risk factors of VFs was evaluated. For measurement of bone mineral density we included the assessment of lumbar spine (AP L1-L4) and Femoral Neck by dual-energy X-ray absorptiometry (DXA). VFs were evaluated by lateral vertebral assessment (LVA) of the dorsal and lumbar regions using X-ray and digital vertebral morphometry by DXA, using the Genant scale. Serum irisin levels were measured by ELISA. A reference group of 97 women with non-rheumatic diseases were included to compare irisin levels.RA patients had a median age of 59 years and 41% had osteoporosis. Seventy three (49%) had VFs. Lower irisin levels were observed in RA patients compared to controls (94 ± 74 vs 135 ± 103, P < .001). Irisin concentrations were lower in RA + VFs than RA non-VFs (74 ± 42 vs 113 ± 92 ng/mL, P = .001). In the multivariable logistic regression analysis the low 50 percentile irisin levels < 73 ng/mL (OR:3.1, 95% CI:1.55-6.2, P = .001), and disease duration of RA (OR:1.04, 95% CI:1.001-1.08, P = .04) were associated with an increase in the risk of VFs.A decrease of irisin levels is associated to VFs in RA. These results are valuable to consider that RA patients with low levels of irisin are in a potential risk of VFs.

Background. Myostatin is a regulator of muscle size. To date, there have been no published studies focusing on the relation between myostin levels and myopenia in rheumatoid arthritis (RA). Objective. Evaluate the value of serum myostatin as a biomarker of cachexia and low skeletal muscle mass (LSMM) in RA patients, along with whether high serum myostatin is associated to these conditions after adjusting for potential confounders. Methods. This cross-sectional study included 161 female RA patients and 72 female controls. In the RA group, we assessed several potential risk factors for LSMM and rheumatoid cachexia. Dual-energy X-ray absorptiometry was used to quantify the skeletal muscle mass index (SMMI) (considering LSMM ≤ 5.5  kg/m2) and the presence of rheumatoid cachexia (a fat-free mass index ≤ 10 percentile and fat mass index ≥ 25 percentile of the reference population). Serum myostatin concentrations were determined by ELISA. To identify a cut-off for high serum myostatin levels, we performed ROC curve analysis. Multivariable logistic regression analysis was used to identify the risk factors for LSMM and rheumatoid cachexia. The risk was expressed as odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results. Compared to the controls, the RA group had a higher proportion of LSMM and exhibited high serum myostatin levels ( p < 0.001 ). ROC curve analysis showed that a myostatin level ≥ 17  ng/mL was the most efficient cut-off for identifying rheumatoid cachexia (sensitivity: 53%, specificity: 71%) and LSMM (sensitivity: 43%, specificity: 77%). In the multivariable logistic regression, RA with high myostatin levels (≥17 ng/mL) was found to increase the risk of cachexia ( OR = 2.79 , 95% CI: 1.24-6.29; p = 0.01 ) and LSMM ( OR = 3.04 , 95% CI: 1.17-7.89; p = 0.02 ). Conclusions. High serum myostatin levels increase the risk of LSMM and rheumatoid cachexia. We propose that high myostatin levels are useful biomarkers for the identification of patients in risk of rheumatoid cachexia and myopenia.

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = − 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

BackgroundTo date, there is controverted the association between serum macrophage migration inhibitory factor (MIF) and serum adipokines with Lupus Nephrites.ObjectiveTo investigate the value of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritisMethodsDesign: cross-sectional. We included 196 Systemic Lupus Erythematosus (SLE) and 52 controls (HC). In SLE, disease activity was assessed by SLEDAI. Renal involvement was investigated by Renal-SLEDAI: a) Renal-SLE involvement (n=43) and b) Non-Renal-SLE (n=153). MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed correlations of MIF, adipokines and renal involvement parameters [proteinuria (g/day), serum creatinine and other]. Multivariable linear regression was used for investigating factors associated with the intensity of proteinuria. ResultsSLE patients had higher MIF (p=0.02) and adiponectin levels (p<0.001) than HC. In renal-SLE involvement there were higher adiponectin levels (19.0 vs 13.3 µg/mL, p=0.002) and resistin levels (10.7 vs 8.9 ng/mL, p=0.01), compared with non-Renal-SLE. Proteinuria correlated with high adiponectin (rs=0.19, p<0.009) and resistin levels (rs=26, p<0.001). MIF (rs=0.27, p=0.04) and resistin (rs= 0.18; p=0.02) correlated with increased creatinine. High Renal activity correlated with adiponectin (rs=0.21, p=0.004). Multiple linear regression identified that elevated adiponectin (p=0.02), younger age (p=0.04) and low MIF (p=0.02) were associated with intensity of proteinuria. Low MIF and high adiponectin levels have interaction for intensity of proteinuria (R2=0.41). ConclusionsHigh adiponectin combined with low MIF concentrations interacts for increase proteinuria in renal-SLE, and MIF and resistin levels are associated with renal dysfunction. These findings highlight the relevance of including the assessment of MIF and adipokines as clinical markers in the evaluation of LN.