scholarly journals Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tong-ling Yuan ◽  
Jin Chen ◽  
Yan-li Tong ◽  
Yan Zhang ◽  
Yuan-yuan Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Heme Oxygenase ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Tartrate Resistant Acid Phosphatase ◽  
Trap 5B ◽  
Potential Biomarkers

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling.Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism.Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p<0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p<0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p<0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p<0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort.Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

scholarly journals Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model

2021 ◽  
Vol 28 (4) ◽  
pp. 307-316
Author(s):  
Majed G. Alrowaili ◽  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Mohamed S. Serria ◽  
Hussein Abdellatif ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Bone Mineral ◽  
Serum Levels ◽  
Male Rats ◽  
Control Group ◽  
Intermittent Fasting ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Trap 5B

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

scholarly journals FRI0373 ASSOCIATIONS OF VASCULAR PATHOPHYSIOLOGY AND BONE METABOLISM IN ANTI-TNF- TREATED RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 783.2-784
Author(s):  
M. Czókolyová ◽  
K. Gulyás ◽  
Á. Horváth ◽  
E. Végh ◽  
Z. Pethö ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Certolizumab Pegol ◽  
Univariate Analysis ◽  
Inflammatory Rheumatic Diseases ◽  
Ageing Population ◽  
Research Support ◽  
Vascular Markers

Background:Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the ageing population, even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthropathies. Both RA and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss, accelerated atherosclerosis, increased CV morbidity and mortality.Objectives:Bone and vascular biomarkers and parameters along with the effect of one-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS.Methods:Fifty-three patients including 36 RA patients treated with etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were assessed by ELISA. Bone density was assessed by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and pulse-wave velocity (PWV) were assessed by ultrasound. The effects of vascular markers on bone and bone effects on vasculature undergone statistical analysis.Results:Serum levels of vascular endothelial growth factor (VEGF), PDGF-BB, angiopoietin 2 (Ang2) and cathepsin K (CathK) decreased, procollagen type 1 N-propeptide (P1NP) and sclerostin (SOST) levels increased, soluble receptor activator nuclear kappa B ligand (sRANKL) and osteoprotegerin (OPG) levels showed no differences. When bone and vascular markers were correlated with each other, at baseline, OPG correlated with Ang2 and adiponectin. SOST correlated positively with ccIMT. DXA L2-4 BMD, DXA L1 BMD and DXA femoral neck (FN) BMD correlated with FMD and CRP. QCT trabecular BMD correlated with ccIMT and PON1. According to the univariate analysis, FMD correlated with OPG, ccIMT correlated with SOST and QCT trabecular BMD. Ang1, Ang2 and PDGF-BB showed correlation with Dickkopf-1 (DKK1). Ang2 also correlated with OPG. As suggested by the multivariate analysis, OPG determined FMD; DKK1 was an independent predictor of Ang1, Ang2 and PDGF-BB. OPG was a predictor of Ang2.Conclusion:In our study of anti-TNF treated RA and AS patients, vascular and bone parameters showed numerous correlations. The therapy was clinically effective, it halted further bone loss over 1 year and reduced the production of angiogenic markers.Acknowledgments:This research was supported by an investigator-initiated research grant from Pfizer.Disclosure of Interests:Monika Czókolyová: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Szilvia Szamosi: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Emese Balogh: None declared, Nóra Bodnár: None declared, Levente Bodoki: None declared, Agnes Szentpetery: None declared, Harjit Pal Bhattoa: None declared, György Kerekes: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Sándor Szántó: None declared, Gabriella Szücs: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen

Bortezomib Reduces Serum Dickkopf-1 and RANKL Concentrations and Normalizes Indices of Bone Remodeling in Patients with Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 506-506
Author(s):  
Evangelos Terpos ◽  
Deborah Heath ◽  
Amin Rahemtulla ◽  
Kostas Zervas ◽  
Andrew Chantry ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Serum Levels ◽  
Response To Therapy ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Lytic Lesions ◽  
Tracp 5B ◽  
Dickkopf 1

Abstract Bortezomib is a proteasome inhibitor, which is currently indicated for the treatment of relapsed/refractory myeloma (MM). Although the anti-myeloma effect of bortezomib has been clearly demonstrated, its effect on bone metabolism is still unclear. There are recent reports that bortezomib increases serum alkaline phosphatase (ALP) activity, which is consistent with enhanced osteoblast function. The aim of this study was to evaluate the effect of bortezomib on bone turnover in 34 patients with relapsed MM. Bortezomib was given alone at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of a 3-week cycle for 4 cycles. Responders could continue for 4 more cycles, while non-responders could continue therapy with the addition of dexamethasone. The following serum indices were measured on day 1 of cycle 1, and then on day 21 of cycles 4 and 8: osteoblast inhibitor dickkopf-1 (DKK-1); osteoclast regulators: soluble RANKL (sRANKL) and osteoprotegerin (OPG); bone resorption markers: C-telopeptide of collagen type-I (CTX) and tartrate-resistant acid phosphatase type-5b (TRACP-5b); and bone formation markers: bone-specific ALP (bALP) and osteocalcin (OC). We also studied 33 healthy controls of similar gender and age. The objective response rate after 4 cycles of therapy was 66%: CR 8% and PR 58%. Sixteen responders and 3 non-responders continued on therapy for 4 more cycles. Myeloma patients at baseline had increased values of DKK-1 (p=0.007), sRANKL, sRANKL/OPG ratio, and both markers of bone resorption (p&lt;0.0001) when compared to controls. In contrast, bone formation as assessed by serum bALP and OC was significantly reduced (p&lt;0.001). There was a strong correlation between bone lytic disease and serum CTX (r=0.59, p&lt;0.01), and sRANKL (r=0.4, p=0.03). Patients with severe bone disease (&gt;9 lytic lesions, n=7) had elevated values of DKK-1 compared with all others (mean±SD: 223.4±264.4 ng/mL vs. 84±62.4 ng/mL; p=0.01). Moreover, serum levels of DKK-1 correlated with CTX levels (r=0.39, p=0.04), and weakly with bALP concentrations (r=−0.32, p=0.09). The administration of bortezomib produced a significant reduction of DKK-1 (p=0.035), sRANKL (p=0.01), CTX and TRACP-5b (p&lt;0.001) after 4 cycles, which was still seen after 8 cycles of treatment (p&lt;0.01). Bortezomib also produced a dramatic increase in both markers of bone formation, bALP and OC, after 4 and 8 cycles of therapy (p&lt;0.01). Responders tended to have lower initial levels of DKK-1 compared with non-responders. Patients who achieved a CR or vgPR after 4 cycles of bortezomib had greater elevation of bALP than all others: mean±SD of increase: 306.3%±556.9% vs. 45.8%±56.5%; p=0.02. It is of interest that 3/4 non responders also had an increase in bALP (mean: 39.6%) after 4 cycles of bortezomib. There was no other correlation between response to therapy and alteration of bone markers. No healing of the lytic lesions was observed even in CR patients. This study suggests that bortezomib reduces serum levels of DKK-1 and RANKL, irrespective of response to therapy, in patients with relapsed myeloma and thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption.

Decidual expression and maternal serum levels of heme oxygenase 1 are increased in pre-eclampsia

2008 ◽  
Vol 87 (3) ◽  
pp. 272-279 ◽  
Author(s):  
Irina P. Eide ◽  
Christina V. Isaksen ◽  
Kjell Å. Salvesen ◽  
Mette Langaas ◽  
Svanhild A. Schønberg ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Serum Levels ◽  
Maternal Serum ◽  
Heme Oxygenase 1

scholarly journals Increased level of heme oxygenase-1 in rheumatoid arthritis synovial fluid

2011 ◽  
Vol 21 (2) ◽  
pp. 150-157 ◽  
Author(s):  
Ai Kitamura ◽  
Keiichiro Nishida ◽  
Takamitsu Komiyama ◽  
Hideyuki Doi ◽  
Yasutaka Kadota ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Rheumatoid Arthritis Synovial Fluid

scholarly journals Heme Oxygenase-1 and Neopterin Plasma/Serum Levels and their role in Diagnosing Active and Latent TB among HIV/TB Co-Infected Patients

2019 ◽  
Author(s):  
Uwimaana Esther ◽  
Bernard S Bagaya ◽  
Barbara Castelnuovo ◽  
David P Kateete ◽  
Anguzu Godwin ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Heme Oxygenase ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Heme Oxygenase 1 ◽  
Hiv Patients ◽  
Receiver Operating Characteristic Curves ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background: Tuberculosis(TB) diagnosis in the presence of HIV co-infection remains challenging. Heme oxygenase 1(HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Infection of macrophages with Mycobacterium tuberculosis (M .tb ) causes the production of HO-1 and neopterin and previous studies have shown these to be markers of immune activation. This study was conducted to determine the levels of HO-1 and neopterin and their utility in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis(COHSONET) study and the Kampala TB Drug Resistance Survey(KDRS). Methods: A total of 210 participants were enrolled in a study of a diagnostic method aimed at determining the levels of HO-1 and neopterin and determine their diagnostic accuracy as biomarkers in TB diagnosis from March to May 2019. M. tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection(LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using Kruskal Wallis and Receiver Operating Characteristic curves to determine the diagnostic accuracy. Results: HO-1 levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 10.7ng/ml (IQR: 7.3-12.7ng/ml), 7.5ng/ml (IQR: 5.4-14.1ng/ml), 3.3ng/ml (IQR: 2.0-7.1ng/ml) respectively. Neopterin levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 11.7ng/ml (IQR: 5.219.4ng/ml), 8.8ng/ml (IQR: 2.4-19.8ng/ml), and 5.9ng/ml (IQR: 3.410.2ng/ml) respectively. HO-1 showed a sensitivity of 78.57% and a specificity of 71.43% with area under the curve(AUC) of 0.839 when used to diagnose ATB. HO-1 showed AUC of 0.79, sensitivity of 70% and specificity 70% when used to diagnose LTB. Neopterin showed a sensitivity of 61.43% and a specificity of 74.29% with AUC 0.71 when used to diagnose ATB. Neopterin as a biomarker in LTB diagnosis showed AUC of 0.56 which was not significant. Conclusion: HO-1 and neopterin are valuable diagnostic biomarkers for ATB and LTB which could be further utilized to develop less costly rapid diagnostic tools to overcome current TB diagnostic challenges.

Biomarkers of Bone Metabolism in Ankylosing Spondylitis in Relation to Osteoproliferation and Osteoporosis

2014 ◽  
Vol 41 (7) ◽  
pp. 1349-1356 ◽  
Author(s):  
Eva Klingberg ◽  
Merja Nurkkala ◽  
Hans Carlsten ◽  
Helena Forsblad-d’Elia
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Bone Metabolism ◽  
Activity Index ◽  
Elevated Serum ◽  
Serum Levels ◽  
Spinal Mobility ◽  
C Reactive Protein ◽  
Mineral Density ◽  
Reactive Protein

Objective.To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, back mobility, osteoproliferation, and bone mineral density (BMD).Methods.Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-energy x-ray absorptiometry.Results.Two hundred four patients with AS (NY criteria; 57% men), with a mean age of 50 ± 13 years and disease duration 15 ± 11 years, and 80 age and sex-matched controls were included. The patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (rS = −0.21, p = 0.003) and DKK-1 (rS = −0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age.Conclusion.Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.

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