Pongsak Yuktanandana

Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients

BackgroundOsteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity.MethodsThirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay.ResultsThe average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001).ConclusionsDkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.

Correlation of plasma and synovial fluid osteopontin with disease severity in knee osteoarthritis

OBJECTIVES The purposes of this study were to examine osteopontin levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease. DESIGN AND METHODS Thirty-two patients aged 53-83 years with knee OA and 15 healthy controls were enrolled in this study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. Osteopontin levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. RESULTS The mean plasma osteopontin concentration of the knee OA patients was significantly higher compared with that of healthy controls (168.8+/-15.6 vs 67.2+/-7.7 ng/mL, P<0.0001). Osteopontin levels in synovial fluid were significantly higher with respect to paired plasma samples (272.1+/-15.0 vs 168.8+/-15.6 ng/mL, P<0.001). In addition, plasma osteopontin levels showed a positive correlation with synovial fluid osteopontin levels (r=0.373, P=0.035). Subsequent analysis showed that plasma osteopontin levels significantly correlated with severity of disease (r=0.592, P<0.001). Furthermore, the synovial fluid levels of osteopontin also correlated with disease severity (r=0.451, P=0.01). CONCLUSION The data suggest that osteopontin in plasma and synovial fluid is related to progressive joint damage in knee OA. Osteopontin may serve as a biochemical marker for determining disease severity and could be predictive of prognosis with respect to the progression of knee OA.

Association between matrix metalloproteinase-3 polymorphism and anterior cruciate ligament ruptures.

Anterior cruciate ligament (ACL) ruptures are considered to be the most severe joint injury in sports. However, the precise etiologies of ACL injuries are not fully understood. Recently, the gene encoding the matrix metalloproteinase-3 (MMP-3, stromelysin-1) was shown to be associated with anterior cruciate ligament ruptures. The 5A/6A polymorphism in the promoter of the MMP-3 gene affects the regulation of MMP-3 gene expression. We examined the association between polymorphism within -1612 of the MMP-3 gene and ACL rupture in an independent population. Eighty-six participants between 20 and 40 years of age with surgically diagnosed ACL ruptures and 100 healthy controls between 18 and 28 years of age without history of ligament or tendon injuries were recruited for the study. All participants were genotyped for the MMP-3 polymorphism (-1612 5A/6A). Statistical analyses of genotype frequencies between patients and healthy controls were performed by the chi-square test. A significant difference was found between ACL rupture subgroups in terms of genotype association (5A+ (5A/5A, 5A/6A): 37.5% in contact sports vs 20% in non-contact sports; P = 0.02). In allelic association, there were significant differences (6A: 81.2% in contact sports vs 89.1% in non-contact sports, 5A: 18.8% in contact sports vs 10.9% in non-contact sports, P = 0.01). The 5A+ genotype of MMP-3 was represented in ACL ruptures in contact sport participants. We propose that this sequence variant is a specific genetic element that should be included in a multifactorial model to understand the etiologies and risk factors for ACL rupture.

Plasma and synovial fluid connective tissue growth factor levels are correlated with disease severity in patients with knee osteoarthritis

Background: Connective tissue growth factor (CTGF) has been implicated in development of osteoarthritis (OA). Objective: To determine the correlation between plasma and synovial fluid CTGF levels and the severity in knee osteoarthritis patients. Methods: A total of 100 subjects were recruited into this study (75 OA patients and 25 controls). CTGF concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. Results: Plasma and synovial fluid CTGF concentrations were correlated with radiographic severity. There was a positive correlation between plasma and synovial fluid CTGF levels. Conclusion: CTGF could be useful for monitoring the severity and progression of OA.

Oxidative Stress, Vitamin E, and Antioxidant Capacity in Knee Osteoarthritis

BACKGROUND Osteoarthritis (OA) is a chronic progressive degenerative joint disorder which is characterised by strongly age-related regressive changes in articular cartilage. The objective of this study was to evaluate oxidative stress and antioxidant parameters in plasma and synovial fluid of patients with primary knee osteoarthritis. MATERIAL AND METHODS Thirty-five OA patients and 35 healthy controls were recruited for this study. Nitrite, malondialdehyde (MDA), vitamin E, Trolox Equivalent Antioxidant Capacity (TEAC), and Ferric Reducing Antioxidant Power (FRAP) levels in plasma and synovial fluid were determined. RESULTS Plasma nitrite levels in OA patients were significantly higher than those in healthy controls (p = 0.037). Furthermore, plasma MDA levels were significantly higher in OA patients than those in healthy controls (p < 0.001). Moreover, plasma vitamin E levels in OA patients were significantly lower than those in healthy controls (p < 0.001). Synovial fluid vitamin E levels of OA patients were significantly lower than paired plasma samples (p < 0.001). The total antioxidant capacities, as were measured by TEAC and FRAP assays in plasma of OA patients, were significantly lower than those in healthy controls (p < 0.01). MDA concentrations were positively correlated with nitrite concentrations but they were negatively associated with vitamin E and TEAC levels in synovial fluid of OA patients. CONCLUSION The increased plasma levels of nitrite and MDA and the decreased plasma levels of vitamin E, TEAC, and FRAP indicated that oxidative stress was present in OA patients. These findings suggest that oxidative stress plays a potential role in pathophysiology of knee osteoarthritis.

Association of plasma and synovial fluid interferon-γ inducible protein-10 with radiographic severity in knee osteoarthritis

OBJECTIVES The objective of this study was to investigate interferon-γ inducible protein-10 (IP-10) concentrations in plasma and synovial fluid of patients with knee osteoarthritis (OA) and to analyze their relationship with disease severity. DESIGN AND METHODS Forty OA patients and 15 healthy controls were enrolled in this study. OA grading was performed according to the Kellgren-Lawrence criteria. IP-10 levels in plasma and synovial fluid were assessed using enzyme-linked immunosorbent assay. RESULTS Plasma IP-10 levels in the knee OA patients were significantly lower than those of controls (P=0.006). IP-10 levels in plasma were markedly higher with regard to paired synovial fluid (P<0.001). Furthermore, IP-10 concentrations in plasma and synovial fluid displayed significant inverse correlation with radiographic severity (r=-0.713, P<0.001 and r=-0.561, P<0.001, respectively). Subsequent analysis revealed that plasma IP-10 levels were positively correlated with synovial fluid IP-10 levels (r=0.424, P=0.006). CONCLUSIONS IP-10 levels in both plasma and synovial fluid were inversely associated with the severity of knee OA. Accordingly, IP-10 could serve as a biomarker for determining disease severity and might play a possible role in the pathophysiology of osteoarthritis.

Plasma and synovial fluid sclerostin are inversely associated with radiographic severity of knee osteoarthritis

OBJECTIVE The purpose of this study was to analyze sclerostin in plasma and synovial fluid of knee osteoarthritis (OA) patients and to investigate the association between sclerostin levels and radiographic severity. DESIGN AND METHODS A total of 190 subjects (95 knee OA patients and 95 healthy controls) were recruited in the present study. Sclerostin levels in plasma and synovial fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren-Lawrence classification. RESULTS Plasma sclerostin levels were significantly lower in OA patients than in healthy controls (P=0.004). Additionally, sclerostin levels in plasma were significantly higher with respect to paired synovial fluid (P<0.001). Moreover, sclerostin levels in plasma and synovial fluid demonstrated a significant inverse correlation with the radiographic severity of knee OA (r=-0.464, P<0.001 and r=-0.592, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and synovial sclerostin levels (r=0.657, P<0.001). CONCLUSIONS Sclerostin was significantly lower in OA plasma samples when compared with healthy controls. Plasma and synovial fluid sclerostin levels were inversely associated with the radiographic severity of knee OA. Therefore, sclerostin may be utilized as a biochemical marker for reflecting disease severity in primary knee OA.

Plasma and synovial fluid inflammatory cytokine profiles in primary knee osteoarthritis.

Abstract Objective: The objective of this study is to compare inflammatory cytokine levels in primary knee osteoarthritis (OA) patients and healthy controls. Methods: A total of 32 knee OA patients and 14 healthy controls were enrolled. A multiplex immunoassay was utilized for 10 cytokines in plasma and synovial fluid. Results: Plasma IL-2, IL-4, and IL-6 concentrations were significantly greater in knee OA patients than controls. Moreover, both plasma IL-4 and IL-6 were positively correlated with the radiographic severity of knee OA. Conclusions: Plasma IL-4 and IL-6 may serve as biomarkers reflecting the severity of OA.

Elevated Circulating and Synovial Fluid Endoglin Are Associated with Primary Knee Osteoarthritis Severity

BACKGROUND AND AIMS Osteoarthritis (OA) is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. The aim of this study was to evaluate endoglin levels in both plasma and synovial fluid of patients with primary knee OA and to determine their relationship with disease severity. METHODS Thirty nine patients with primary knee OA and 15 healthy controls were recruited in this study. The radiographic grading of OA in the knee was performed using the Kellgren and Lawrence classification. Endoglin concentrations in both plasma and synovial fluid were analyzed using a sandwich enzyme-linked immunosorbent assay. RESULTS The average value of plasma endoglin in patients with knee OA was significantly higher compared with that of healthy controls (5.16+/-0.22 vs. 4.43+/-0.3 ng/mL, p=0.03). Although endoglin levels in synovial fluid were higher with respect to paired plasma samples, the difference was not significant (5.41+/-0.32 vs. 5.16+/-0.22 ng/mL, p=0.3). Additionally, plasma endoglin levels exhibited a positive correlation with synovial fluid endoglin levels (r=0.52, p=0.001). Further analysis revealed that plasma endoglin levels significantly correlated with disease severity (r=0.38, p=0.02). Furthermore, the synovial fluid levels of endoglin also positively correlated with disease severity (r=0.55, p=0.001). CONCLUSIONS These findings indicate that endoglin in plasma and synovial fluid is correlated with progressive joint damage in knee OA. Endoglin is likely to be useful as a biomarker for determining disease severity and may play a possible role in the pathogenesis of osteoarthritis.

Impact of bone marker feedback on adherence to once monthly ibandronate for osteoporosis among Asian postmenopausal women.

Aim:  This study assesses the impact of serum carboxy‐terminal collagen crosslinks (CTX) bone marker feedback (BMF) on adherence to ibandronate treatment in Asian postmenopausal women with osteoporosis.AIM This study assesses the impact of serum carboxy-terminal collagen crosslinks (CTX) bone marker feedback (BMF) on adherence to ibandronate treatment in Asian postmenopausal women with osteoporosis. METHODS This was a 12-month (6-monthly phased), randomized, prospective, open-label, multi-center study conducted in 596 (of 628 enrolled) postmenopausal women with osteoporosis (< or = 85 years old) who were naïve, lapsed, or current bisphosphonate users. Patients were randomized into two arms: serum CTX BMF at 3 months versus no-BMF. Once-monthly 150 mg ibandronate tablet was administered for 12 months and adherence to therapy was assessed at 6 and 12 months. In addition, patient satisfaction and safety of ibandronate treatment were also assessed. RESULTS Serum CTX BMF at 3 months showed no impact on adherence. The proportions of adherent patients were comparable in the BMF versus no-BMF arms (92.6%vs. 96.0%, P = 0.16); overall, serum CTX levels were similar for adherent and non-adherent patients. However, BMF patients felt more informed about their osteoporosis (P < 0.001) and more satisfied (P < 0.01) than no-BMF patients. CONCLUSIONS The Asian postmenopausal osteoporosis patients in this study had a high adherence rate to once-monthly ibandronate therapy. Use of serum CTX BMF had no further impact on increasing adherence, but increased treatment satisfaction.