Osteopontin Levels In Patients Research Articles

Osteopontin as a biochemical marker and severity indicator for idiopathic hip osteoarthritis.

A diagnostic evaluation of the severity and progression of hip osteoarthritis (OA) using biochemical markers is lacking in the current medical literature. Osteopontin (OPN) has been proved to correlate with the progression and severity of knee OA. Therefore, the examination of plasma OPN levels in patients with idiopathic hip OA and its correlation with disease severity and progression was necessary. Our study included 21 patients displaying symptomatic severe idiopathic hip OA; the diagnosis of the disease was based on the checklist of the American College of Rheumatology and the severity was evaluated according to the K-L grading (Kellgran and Lawrence score). 14 patients showed radiological changes according K-L grade 3 (66.66%), and 7 patients showed radiological changes according K-L grade 4 (33.33%). We observed a highly statistically significant increase of plasma OPN levels in comparison with normal referenced values, the cut off value for differentiating between normal people and patients with hip OA was 193.6 ng/ml. Furthermore, the mean of plasma OPN levels in idiopathic hip osteoarthritis patients with K-L grade 4 (362.51 ± 83.31 ng/mL) was greater than those with K-L grade 3 (283.41 ± 56.31 ng/mL), the difference being statistically significant. plasma OPN levels are increased in idiopathic hip OA and are correlated with the severity of the disease.

Comparison of Plasma Osteopontin Levels between Patients with Borderline Ovarian Tumours and Serous Ovarian Carcinoma

Osteopontin (OPN) is a novel biomarker of various cancers including ovarian carcinoma. OPN is a promising adjunct to a major biomarker of ovarian cancer, CA125, in diagnosis, differential diagnosis and prognosis. The aim of our study was to measure the plasma level of OPN and CA125 in patients with borderline ovarian tumours (BOTs), serous ovarian carcinoma, and controls to determine its potential role in the differential diagnosis between serous ovarian carcinoma and BOT. The plasma samples of 66 women were analysed using Luminex technology, designed to simultaneously measure multiple specific protein targets. The mean OPN plasma level for the control group was 23.3 ng/ml; for BOT 26.3 ng/ml; and for patients with serous ovarian carcinoma 59.5 ng/ml. Specifically, there was a significant difference between the OPN levels in patients with ovarian carcinoma and BOT (P < 0.001) as well as controls (P < 0.001). There was no difference between the mean levels of OPN in patients with BOT and the control group (P = 0.286). Using the receiver operating characteristic (ROC), we determined the utility of OPN and CA125 to differentiate between BOT and serous ovarian carcinoma. The area under the ROC curve (AUC) for OPN was 0.793 (95% confidence interval (CI) 0.669–0.917, P < 0.001) and for CA125 0.766 (95% CI 0.626–0.907, P = 0.002). Based on our data, we suggest that OPN can be used as a possible differential diagnostic biomarker to distinguish between malignant serous ovarian carcinoma and BOT.

Endostatin and osteopontin are elevated in patients with both coronary artery disease and aortic valve calcification

BackgroundThe angiostatic factor endostatin (ES) plays an important role as mediator of angiogenesis. Elevated osteopontin (OPN) was associated with valve calcification in healthy individuals. The present study aimed to investigate ES and OPN levels in patients with both coronary artery disease (CAD) and aortic valve calcification (AVC). Methods and resultsIn total 224 non- or ex-smoking patients (161 male, mean age: 61.09±11.02years; 63 female: mean age: 67.49±7.87years) with angiographically verified and quantified CAD were recruited. Serum ES and plasma OPN levels were measured by ELISA and AVC was evaluated by a parasternal short axis view and quantified as non-, mild or moderate/severe. There was a stepwise increase of ES measurable with increasing severity of AVC, independent from age, BMI and CAD-severity (p=0.018; F=4.09). OPN also increased significantly with the grade of AVC severity (p=0.029; F=3.61) but was no longer significant when the co-variables (p=0.31; F=1.18) were inserted. ConclusionsThis is the first study showing an association of ES with AVC in CAD-patients independent from age, BMI and CAD-severity which seems to be of distinct interest when trying to understand the process of heart valve calcification. OPN also correlates with AVC-severity but is mostly dependent on the age of the patients.

Impact of Valve Surgery on Serum Osteopontin Levels in Patients with Mitral Regurgitation

Objective: Osteopontin (OPN), a sialoprotein present within atherosclerotic lesions, especially in calcified plaques, is linked to the progression of coronary artery disease and heart failure. We assessed the impact of valve surgery on serum OPN and left ventricular (LV) function in patients with mitral regurgitation (MR). Methods: Thirty-two patients with severe MR scheduled for surgery were included in the study. Echocardiography markers were assessed preoperatively and at 3 months following the surgery and matched with the serum OPN levels. Results: Valve surgery was associated with a reduction of the ejection fraction (EF) from 55.2 ± 6.3 to 48.8 ± 7.1% after surgery, p < 0.001. Following surgery, the OPN level was significantly higher than preoperatively (mean 245, range 36-2,284 ng/ml vs. 76, 6-486 ng/ml, p = 0.007). Preoperative OPN exhibited a slight negative correlation with the EF (r = -0.35, p = 0.04), and a moderate correlation with vena contracta (r = -0.38, p = 0.02). There were no other meaningful correlations between conventional echocardiographic parameters and OPN. Conclusion: Following valve surgery due to severe MR, patients exhibited a decrease in EF and an increase in OPN levels. The assessment of preoperative OPN failed to strongly predict probable LV dysfunction.

Plasma Osteopontin Levels in Patients with Rheumatoid Arthritis and Relation with Disease Activity

Plasma Osteopontin Levels in Patients with Rheumatoid Arthritis and Relation with Disease Activity

Vascular calcification and plasma levels of osteopontin in patients with chronic kidney disease who are treated by program hemodyalisis

Aim. To examine vascular calcification and plasma levels of osteopontin in patients with chronic kidney disease who are treated by program hemodyalisis Methods and results. 53 patients were treated by renal hemodialysis. In this population the prevalence of abdominal aortic calcification was established using X-ray radiography. In 20 of them multislice computer tomography was conducted. There was a positive correlation between vascular calcification and phosphate levels, phosphate - calcium product. Plasma level of osteopontin in hemodialysis patients was significantly higher than in patients with predialysis stages of chronic kidney disease. Conclusion. Positive correlation between plasma levels of citokine and abdominal aortic calcification may indicate that osteopontin is a marker of vascular calcification in patients, who are treated by program hemodialysis.

Serum levels of osteopontin as a prognostic factor in patients with oral squamous cell carcinoma

Osteopontin (OPN) is a multifunctional glycophosphoprotein that was detected in many carcinomas, and it may have a prognostic role. The aim of this study was to determine osteopontin serum levels in patients with oral squamous cell carcinoma (OSCC) and investigated its correlation with clinicopathological features of tumor. Using an ELISA kit, we assessed and compared the circulating levels of OPN in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. The serum osteopontin level in patients with OSCC was significantly higher (145.8 ± 14.6 ng/ml, n = 45) compared with the healthy controls (53.9 ± 9.6 ng/ml, n = 45, p < 0.001). Mean serum osteopontin level was significantly higher in patients with nodal metastasis (p = 0.03) and higher stage (p = 0.02). Findings of the present study suggest that OPN may have a potential role in pathogenesis of OSCC and it may be used as a tool for monitoring tumor progression.

Serum osteopontin level in patients with rheumatoid arthritis after one year therapy of infliximab

Serum osteopontin level in patients with rheumatoid arthritis after one year therapy of infliximab

Role of osteopontin in differential diagnosis of ovarian tumors

The aim of this study was to evaluate the role of the serum osteopontin (OPN) level as a biomarker for discriminating between malignant and benign ovarian tumors. Furthermore, comparisons with the diagnostic usefulness of the other tests were performed. The study included 114 consecutive women with ovarian tumors (82 benign and 32 malignant) who were referred to our division. A cut-off level of 28.0 ng/mL for OPN showed a sensitivity of 71.87% and a specificity of 89.02%. The area under the receiver-operator curve (ROC) was 0.812. There were no differences in diagnostic utility between OPN and the other studied tests. OPN levels were lower in patients with endometriotic ovarian cysts than in those with other benign ovarian tumors (14.00 vs 19.50 ng/mL; P = 0.018). The difference between the median OPN level in patients with endometriotic cysts (14.0 ng/mL) and those with malignant tumors (40.85 ng/mL) was also statistically significant (P < 0.0001). The calculated OPN/CA-125 ratio was significantly different between patients with endometriotic cysts (median, 0.36; range, 0.05-2.89) and those with other benign tumors (median, 1.25; range, 0.05-5.70) (P = 0.0002). There was also a statistically significant difference in the median OPN/CA-125 ratio between patients with endometrial cysts (median, 0.36; range, 0.05-2.89) and those with malignant tumors (median, 0.12; range, 0.01-3.39) (P = 0.004). The diagnostic utility of OPN is similar to that of ultrasonographic evaluation and CA-125 level assessment. Thus, OPN may be useful in differential diagnosis for less experienced ultrasonographers and is especially valuable for differential diagnosis of endometriotic cysts.

Osteopontin in bone mineral density of very old Brazilians

Recent evidence suggests that changes in plasma levels of osteopontin (OPN) may be a promising marker for early diagnosis of bone disorders. We hypothesized that a frequent OPN gene polymorphism may be useful for identifying very old individuals with alterations in plasma OPN levels and consequently at risk of abnormal bone density scores. Men and women (80years or older) living in the Brazilian Federal District underwent assessments with dual energy X-ray absorptiometry for bone mineral density (BMD) of the femoral neck, femoral head and lumbosacral (L1 to S5) regions. Clinical inspection was performed to assess other physical traits and to exclude co-morbidities (cardiovascular, autoimmunity, infections or neoplastic diseases). Serum concentrations of OPN were determined with an enzyme-linked immunosorbent assay, whereas the A7385G polymorphism (rs1126772) was determined by direct sequencing of a polymerase chain reaction product. Among the two hundred and ten subjects enrolled, no differential scores for bone mineral density could be observed across genotypes, but a greater content of circulating OPN was found among carriers of the A allele (P≤0.05) even after adjustments. Serum OPN levels were negatively correlated with femoral neck density (P=0.050 for BMD; P=0.032 for T scores) but not with scores of the other regions investigated. Analyses with the sample dichotomized to age and body mass revealed that this inverse relationship was noticeable only among those aged within the highest and weighing within the lowest intervals. Our findings indicate elevated circulating osteopontin levels in patients with decreased bone mineral density, consistent with a modest contribution of an OPN allelic variation to its expression. Assessing the clinical relevance of our findings demands forthcoming studies.

Soluble levels of Osteopontin in Patients with Behcet's Disease: Association with Disease Activity and Vascular Involvement

Osteopontin (OPN) is a multifunctional molecule highly expressed in chronic inflammatory and autoimmune diseases. We aimed to assess the plasma OPN levels in Behcet's disease (BD) patients and identify potential associations between these levels with disease activity, severity and clinical manifestations with special emphasis on vascular affection. We studied 55 BD patients and 31 age- and gender-matched healthy controls. Demographic, clinical and serological data were prospectively assessed. Activity and severity of BD were assessed using clinical scores and laboratory parameters. Plasma OPN levels were measured using enzyme-linked immunosorbent assay (ELISA). Plasma OPN levels were significantly higher in patients with BD compared to healthy controls (p < 0.000). The means for plasma OPN levels in active and inactive BD patients were significantly higher than that for the normal controls (with p < 0.000 and p = 0.002 respectively). The mean OPN levels significantly associated with the BD clinical severity score from mild to severe (p = 0.011). BD patients with vascular involvement had significant elevation of plasma OPN levels than those without (P = 0.03). OPN levels positively correlated with severity score, IL6, hsCRP, ESR, leucocytes count and neutrophil count. Plasma OPN levels were higher in BD patients than in healthy controls and were found to be associated with disease activity, severity and vascular involvement. To confirm our results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Significance of Plasma Osteopontin Levels in Patients with Bladder Urothelial Carcinomas

Previous studies have suggested that the plasma level of osteopontin may be a biomarker for cancer metastases and clinical prognosis; however, its role in bladder urothelial carcinoma (BUC) remains unknown. The purpose of this study was to explore the significance of plasma osteopontin levels in evaluating the pathologic features of BUC and its potential as a prognostic marker in BUC patients. A total of 225 patients with BUC were enrolled in this study, and 230 age-matched and sex-matched healthy volunteers were enrolled as control subjects. The histologic classification of BUC, clinical stage of the disease, and plasma osteopontin levels were determined at admission. Patients with non-muscle-invasive BUC underwent transurethral resection, while those with muscle-invasive BUC underwent radical cystectomy. Patients receiving transurethral resection and radical cystectomy were followed up to determine their tumor-free interval and overall survival, respectively. The mean plasma osteopontin levels were significantly higher in BUC patients than in controls, significantly higher in patients with high-grade BUC than in those with low-grade BUC, and significantly higher in patients with muscle-invasive BUC than in those with non-muscle-invasive BUC. Patients with bladder-confined disease had the lowest osteopontin levels, while those with lymph node-positive disease had higher osteopontin levels, and those with metastatic BUC had the highest osteopontin expression. Kaplan-Meier analyses showed that a higher plasma osteopontin level was associated with a lower overall survival rate in muscle-invasive BUC patients receiving radical cystectomy. Our results show that the plasma osteopontin level is associated with the clinical features of BUC and predicts the prognosis of muscle-invasive BUC in patients receiving radical cystectomy.

Osteopontin Contributes to TGF-β1 Mediated Hepatic Stellate Cell Activation

Liver fibrosis is characterized by accumulation of extracellular matrix. Our previous study found that osteopontin (OPN) increased in plasma of cirrhotic patients and indicative of cirrhosis staging. The present study was designed to investigate the expression of OPN in liver tissues and plasma of cirrhotic patients and further explore the role of OPN in human hepatic stellate cell (HSC) activation. We used immunohistochemical staining and enzyme-linked immunosorbent assay to evaluate the expression level of OPN in liver tissues and plasma from cirrhotic patients, respectively. We produced lentivirus particles and infected target cell to manipulate OPN expression. Infection efficiency was determined by real-time RT-PCR and western blot. Cell proliferation was determined using CCK8 assay, and phenotypes of HSC activation were determined by real-time RT-PCR. OPN promoter activity was determined by dual luciferase reporter assay. We found that OPN expression in human cirrhotic liver tissues was upregulated compared to normal controls. In addition, its expression correlated with Child-Pugh classification, MELD score and the occurrence of complications. We further explored OPN level in patients' plasma and showed that its level correlated with transforming growth factor-β1 (TGF-β1). In human HSC cell line LX-2, we found that change of OPN expression level could not only affect the proliferation of cells but also the TGF-β1 mediated HSC activation. Moreover, OPN was increased by TGF-β1 stimulation and regulated by TGF-β1 at transcription level. OPN is upregulated in liver tissues and plasma of cirrhotic patients and promotes TGF-β1 mediated HSC activation.

Arterial stiffness is associated with the severity of atherosclerosis and serum osteopontin levels in patients with symptomatic peripheral arterial disease

Arterial stiffness is associated with the severity of atherosclerosis and serum osteopontin levels in patients with symptomatic peripheral arterial disease

Comparison of Serum Osteopontin Levels in Patients with Stable and Chronic Obstructive Pulmonary Disease and Exacerbation

Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects (62.4±51.9 ng/mL, 36.9±11.1 ng/mL, 30±11 ng/mL, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission (45±52.1 ng/mL, 62.4±51.9 ng/mL, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker (23±5.7 ng/mL, 35.5±17.6 ng/mL, 58.6±47.8 ng/mL, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second (FEV 1%) predicted in healthy controls and stable COPD patients (r=−0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

Prognostic Implication of Plasma Osteopontin Levels in Patients with Chronic Kidney Disease

Aims: To assess (a) plasma osteopontin (pOPN) in a cohort of chronic kidney disease (CKD) patients; (b) the relationship between pOPN and aortic calcification and stiffness, and (c) the association between pOPN and the overall and cardiovascular mortality risk. Methods: pOPN, the abdominal aortic calcification score and pulse wave velocity (PWV) were determined in 94 CKD patients (68 ± 13 years; 60% males; 31% at CKD stages 2–3, 31% at stages 4–5, 38% at stage 5D), prospectively followed for mortality. Results: pOPN was higher in CKD patients than in controls. Interleukin (IL)-6 (r² = 0.086; p = 0.004), CRP (r² = 0.046; p = 0.038), iPTH (r² = 0.065; p = 0.014), albumin (r² = 0.210; p < 0.0001) and statin use (r² = 0.038; p = 0.059) were associated with pOPN. There was no association between pOPN and the aortic calcification score or PWV. During follow-up (969 ± 405 days), 32 patients died. In crude analysis, pOPN >167 ng/ml predicted overall and cardiovascular mortality (p = 0.02 and 0.01, respectively), but this effect was lost after adjustment for albumin or IL-6. Conclusions: pOPN is elevated from the early stages of CKD onward. We found no associations between pOPN and the aortic calcification score or the PWV. The positive association between pOPN and clinical outcomes was dependent of the patients’ inflammatory status.

Osteopontin predicts survival in critically ill patients with acute kidney injury

The cytokine osteopontin is involved in the pathophysiology of experimental acute kidney injury. We have tested the hypothesis that osteopontin levels might serve as a biomarker predicting outcome in critically ill patients requiring renal replacement therapy after acute kidney injury. We measured circulating plasma osteopontin levels in 109 critically ill patients with acute kidney injury at inception of renal replacement therapy and 4 weeks thereafter. Critically ill patients without acute kidney injury served as controls. Osteopontin was measured with ELISA. Baseline osteopontin levels in patients with acute kidney injury were significantly higher compared with controls (P<0.0001). Baseline osteopontin levels in patients recovering from acute kidney injury were significantly elevated compared with patients with permanent loss of kidney function after acute kidney injury (P=0.01). In addition, in patients recovering from acute kidney injury without further need for renal replacement therapy, osteopontin levels were significantly lower 4 weeks after initiation of renal replacement therapy (P=0.0005). Moreover, multivariate Cox analysis revealed osteopontin levels at renal replacement therapy inception as an independent and powerful predictor of mortality (P<0.0001). In the ROC-curve analysis, an osteopontin cut-off value of 577 ng/mL separated survivors from non-survivors with a sensitivity of 100% and a specificity of 61% (AUC 0.82; 95% confidence interval: 0.74-0.89; P<0.0001). Osteopontin may serve as a novel biomarker for both, overall survival and renal outcome in critically ill patients with acute kidney injury, that require renal replacement therapy.

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

Osteopontin (OPN) has recently emerged as a key factor in both vascular remodelling and development of atherosclerosis. It has been reported that OPN is regulated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to clarify the effect of angiotensin II receptor blockade with valsartan on plasma OPN levels in patients with essential hypertension (EHT). Forty-six patients (mean age, 64±11 years) with EHT were randomly assigned to treatment with amlodipine or valsartan. There were no significant differences in baseline clinical characteristics between the two groups. Blood sampling and blood pressure evaluation were performed before and after 24 weeks of treatment. After 24 weeks, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were decreased significantly and by the same degree in each treatment group. However, valsartan but not amlodipine decreased plasma OPN levels (baseline and 24-week data-valsartan: 614±224 ng ml(-1), 472±268 ng ml(-1), P=0.006; amlodipine: 680±151 ng ml(-1), 687±234 ng ml(-1), P>0.999). A positive correlation between the reduction in OPN and the log natural (ln) C-reactive protein (CRP) was seen in the valsartan-treated group. Stepwise regression analysis showed that treatment with valsartan and the reduction of ln CRP were associated with the reduction in OPN levels, and this association was independent of the reduction in SBP or aldosterone levels (valsartan: β=0.332, P=0.026; ln CRP reduction: β=0.366, P=0.015). These results suggest that suppression of the RAAS and inflammation may decrease plasma OPN levels.

Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease

The aim of this study was to compare the results of semiquantitative analysis by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) with plasma osteopontin levels in the same asbestos-related pleural disease population. A total of 17 patients with asbestos-related pleural disease were prospectively recruited. They underwent PET/CT, and plasma osteopontin levels were measured. The maximum standardized uptake value (SUVmax) was determined from the most active pleural lesion in each patient. Malignant pleural mesothelioma (MPM) was histologically proven in 6 patients, and 11 patients had proven benign asbestos-related pleural diseases (7 pleural plaques, 4 asbestos pleurisy). Significant differences in SUVmax were found between patients with MPM and those with asbestos pleurisy (P = 0.031) and between patients with MPM and those with pleural plaques (P = 0.012). A significant difference was found in the plasma osteopontin levels between patients with asbestos pleurisy and patients with pleural plaques (Bonferroni correction, P = 0.024). The SUVmax in patients with benign asbestos-related diseases was statistically positively correlated with plasma osteopontin in the same group (Spearman's r = 0.75, P < 0.05). PET/CT might be more helpful than plasma osteopontin for distinguishing benign asbestos-related pleural diseases from MPM, and the SUVmax in benign asbestos-related pleural diseases may reflect changes in pleural inflammation.

Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3‐year follow‐up study

Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD). In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 2.25, maximum 3.9 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons. Baseline lnOPN levels were directly related to age (r = 0.27, P < 0.001) and inversely to left ventricular ejection fraction (r = -0.32, P < 0.01). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (beta = -0.013, P = 0.02). Median OPN value was 55 ng mL(-1). In the univariate Cox-regression analysis, OPN levels > 55 ng mL(-1) (n = 50) were significantly related to adverse cardiac outcome (HR = 2.40, 95% CI: 1.11-5.23, P = 0.027). In multivariate model, OPN levels > 55 ng mL(-1) remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 2.88, 95% CI: 1.09-7.58, P = 0.032). OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD.