Is there a relationship between dynamic thiol/disulfide homeostasis and osteoarthritis progression?

We aim to determine serum dynamic thiol/disulphide homeostasis with novel methods in early-stage osteoarthritis and late-stage osteoarthritis patients and investigated whether it was associated with the progression of osteoarthritis risk or not. One hundred eighteen patients were included in this prospective study. Osteoarthritis patients were divided into five stages, according to the Kellgren-Lawrence scale. Dynamic thiol/disulphide homeostasis was determined with a novel spectrophotometric method. Late-stage osteoarthritis patients had significantly lower levels of native and total thiol than the patients of early-stage osteoarthritis. Disulphide, index-1, index-2 levels, and WOMAC score of late-stage osteoarthritis patients were significantly higher than the ones belonging to patients of early-stage osteoarthritis. Decreased native thiol and total thiol levels and increased WOMAC score and disulphide levels were independently associated with increased risk of late-stage osteoarthritis. We suggest that both WOMAC score and dynamic thiol/disulphide homeostasis may be implicated in the pathogenesis and progression of osteoarthritis. We also recommend that dynamic thiol/disulphide homeostasis may have clinical utility as possible markers of differential diagnosis of early-stage and late-stage osteoarthritis.

Relationship between increased serum & synovial fluid decorin levels & knee osteoarthritis.

BACKGROUND & OBJECTIVES: Decorin is a proteoglycan that plays a role in the binding of collagen and has an important role in the pathogenesis of osteoarthritis (OA). This study was aimed to determine serum and synovial fluid decorin levels in patients with knee OA and to investigate whether these levels were associated with OA and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. METHODS: In this prospective study 88 participants were included (44 knee OA and 44 with other knee joint diseases) in the study and control groups. Knee function was assessed using the WOMAC score. The serum and synovial fluid decorin levels were analyzed using a human decorin ELISA. Binary logistic regression with a single and multi-categorical predictor was used to determine the possible risk factors for OA. RESULTS: The serum decorin levels were significantly higher in the OA group than the control group (P<0.002).s The synovial fluid decorin levels were not significantly different between OA and control groups. WOMAC score [odds ratio (OR)=1.073, 95% confidence interval (CI): 1.032-1.116, P<0.001] and high serum decorin levels (OR=1.114, 95%CI: 1.030-1.205, P=0.007) were found to be significant in the determination of OA. Serum decorin levels were positively correlated with the WOMAC score in OA. INTERPRETATION & CONCLUSIONS: An increased serum decorin levels may be indicative of changes in extracellular matrix structure. The positive correlation between serum decorin level and WOMAC score supports this result. Increased serum decorin levels and WOMAC score were found to be risk factors associated with OA. However, the decorin level in the joint fluid was not associated with OA.

The utility of synovial fluid levels of ADAMTS9 and ADAMTS4 in predicting treatment responses to intraarticular steroid injections in patients with knee osteoarthritis

Background/aim: This study aims to identify the role of synovial fluid levels of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) for the prediction of intraarticular steroid injection success in knee osteoarthritis (OA). Material and methods: A total of eighty-four advanced stage knee OA patients (42 with stage 3 OA and 42 with stage 4 OA) were enrolled in the study. Baseline and posttreatment outcomes were determined using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pretreatment synovial fluid ADAMTS9 and ADAMTS4 levels were measured by enzyme linked immunosorbent assay (ELISA). ''Total WOMAC score regression of 18% and above'' was taken as a minimal clinically important difference (MCID) to indicate improvement. Determining the best predictors of intraarticular steroid injection success in both groups was evaluated by multiple logistic regression analyses. Results: Synovial fluid ADAMTS9 levels were significantly lower in the stage 4 OA group when compared with the stage 3 group. The level of synovial fluid ADAMTS9 was statistically significantly lower in the WOMAC score percent change ≥18% than the WOMAC score percent change <18% group in Stage 3 OA group (P = 0.026). Decreasing synovial fluid ADAMTS9 levels (odds ratio (OR): 0.625, 95% confidence interval (CI): 0.437­0.893) were found to be predictive for the WOMAC score percent change ≥18 in all OA patients (P = 0.010). Decreasing ADAMTS9 levels in synovial fluid (OR: 0.602; 95% CI = 0.372­0.974) were predictive for MCID in stage 3 OA patients (P = 0.039). Conclusion: The lower levels of ADAMTS9 in synovial fluid may be used in conjunction with high WOMAC scores in the prediction of intraarticular steroid injection success and advanced stage knee OA patients.

The Association of Ischemia Modified Albumin with Osteoarthritis Progression.

BACKGROUND: We suggested a relationship between increased serum IMA (ischemia-modified albumin) levels and cartilage degeneration. We proposed that the increased serum levels of IMA was due to the oxidative stress mechanism against ongoing cartilage degeneration in osteoarthritis (OA) and thus may be associated with the progression of OA. We aimed to investigate serum IMA levels in OA patients and determine whether any changes in IMA levels are useful as a marker in increased OA. METHODS: A prospective case-control study was carried out, which included 110 patients (55 patients with OA and 55 healthy controls). Serum samples obtained from all participants and IMA levels were determined by spectrophotometric method. RESULTS: Compared with controls, OA had significantly higher IMA and IMA/albumin (IMAR) levels (0.732 ± 0.078 vs. 0.773 ± 0.080, p  = 0.008; 0.188 ± 0.20 vs. 0.176 ± 0.21; p = 0.011). Multivariable logistic regression analysis revealed rising IMA and IMAR levels were independently associated with OA (OR: 1.755, 95% CI: 0.655 - 4.700, p = 0.009 and OR = 3.021, 95% CI: 0.258 - 3.525, p = 0.015). CONCLUSIONS: The current study suggests that increased levels of IMA are associated with OA and are a probable predictive risk marker for the progression of OA.

The role of increased synovial fluid A disintegrin and metalloproteinase with thrombospondin motifs4 and serglycin levels in osteoarthritis.

BACKGROUND: The first research to determine synovial fluid ADAMTS4 and serglycin levels in osteoarthritis and OA progression. AIM: We aimed to determine ADAMTS4 and serglycin levels, interactions, and changes in the synovial fluid of knee OA, and also to determine effective in OA progression. METHODS: A case-control study was carried out including a total of 88 participants (29 patients late OA [LOA], 28 early OA [EOA], and 30 controls). Synovial fluid serglycin and ADAMTS4 levels were measured by commercially available ELISA kits, and knee functions of the patients were evaluated with The Western Ontario and McMaster Universities Osteoarthritis score (WOMAC). Logistic regression analysis was applied for the associated with progression of OA. RESULTS: Synovial fluid ADAMTS4 and serglycin levels were significantly higher in LOA than EOA and control groups (p < .001 and p < .001; p = .038 and p = .007, respectively). All parameters were evaluated after adjustment for age. LOA patients had significantly higher levels of WOMAC score than EOA and controls (p < .001 and p < .001). According to the logistic regression analysis, synovial fluid ADAMTS4, serglycin levels, and WOMAC score were found to be significantly associated with progression of OA.

Serum and knee synovial fluid matrixmetalloproteinase-13 and tumor necrosis factor-alpha levels in patients with late stage osteoarthritis.

OBJECTIVE: To compare the levels of MMP-13 and TNF-α in late stage osteoarthritis, define their predominant pathways and investigate their correlation with McMaster Universities Arthritis Index scores. PATIENTS AND METHODS: A total of 42 patients (mean age 64 ± 8.8) with grade 3 and grade 4 knee osteoarthritis according to Kellegren- Lawrence criteria and who were scheduled for total knee arthroplasty were enrolled in the study. TNF-alpha and MMP-13 levels were measured preoperatively from venous blood samples and intraoperatively from knee synovial fluid via ELISA. Preoperative and 1 month postoperative knee functions were assessed by McMaster Universities Arthritis Index. RESULTS: Grade 4 synovial fluid MMP-13 (4.76 ± 5.82) was elevated compared to grade 3 (3.95 ± 4.45) (p = 0.438), whereas grade 3 serum MMP-13 (1.128 ± 0.308) was found elevated compared to grade 4 (1.038 ± 0.204) (p = 0.430). Grade 4 serum TNF-α (0.253 ± 0.277) was elevated compared to grade 3 (0.206 ± 0.219) whereas grade 3 synovial fluid TNF-α (0.129 ± 0.052) was elevated compared to grade 4 (0.118 ± 0.014). Positive correlation was observed between synovial fluid MMP-13 levels and postoperative WOMAC scores. Mean serum TNF-α level (0.226 ± 0.246 pg/ml) was found higher compared to synovial level (0.124 ± 1.59), synovial MMP-13 level (4.31 ± 1.24) was found higher compared to serum level (1.089 ± 1.519). CONCLUSION: Despite the systemic increase in TNF-α levels concordant with osteoarthritis grade, MMP-13 levels are elevated via local manner with a significant correlation with WOMAC scores. LEVEL OF EVIDENCE: Level IV, Diagnostic study.

Serum and knee synovial fluid matrix metalloproteinase-13 and tumor necrosis factor-alpha levels in patients with late-stage osteoarthritis.

OBJECTIVE: The aim of this study was to compare serum and synovial fluid levels of matrix metalloproteinase-13 (MMP-13) and tumor necrosis factor-alpha (TNF-α) in 2 stages of osteoarthritis, and investigate their correlation with Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. METHODS: Forty-two patients (mean age: 64±8.8 years) with grade 3 and grade 4 knee osteoarthritis according to Kellgren-Lawrence criteria were enrolled in the study and underwent total knee arthroplasty. TNF-α and MMP-13 levels were measured preoperatively from venous blood samples and intraoperatively from knee synovial fluid via enzyme-linked immunosorbent assay. Preoperative and 1-month postoperative knee functions were assessed by WOMAC. RESULTS: Grade 4 synovial fluid MMP-13 (4.76±5.82 pg/ml) was elevated compared to grade 3 (3.95±4.45), whereas grade 3 serum MMP-13 (1.128±0.308 pg/ml) was found elevated compared to grade 4 (1.038±0.204) (p=0.438, p=0.430, respectively). Grade 4 serum TNF-α (0.253±0.277) was elevated compared to grade 3 (0.206±0.219), whereas grade 3 synovial fluid TNF-α (0.129±0.052) was elevated compared to grade 4 (0.118±0.014). Positive correlation was observed between synovial fluid MMP-13 levels and postoperative WOMAC scores. Mean serum TNF-α (0.226±0.246 pg/ml) was elevated compared to synovial levels (0.124±1.59), and synovial MMP-13 (4.31±1.24) was elevated compared to serum levels (1.089±1.519). CONCLUSION: Despite the systemic increase in TNF-α levels concordant with osteoarthritis grade, MMP-13 levels are elevated via local manner, with a significant correlation with WOMAC scores.

Polysaccharide hemostatic system reduces blood loss in high-body-mass-index patients undergoing simultaneous bilateral total knee arthroplasty.

BACKGROUND: To investigate the efficacy of a topically applied hemostatic agent used to reduce blood loss in patients undergoing simultaneous bilateral total knee arthroplasty (TKA). METHODS: Thirty-two patients (5 male, 27 female) mean age 65 ± 9.3 (46-80) undergoing single-stage bilateral TKA were enrolled in the study and divided in two groups. Groups 1 and 2 consisted of patients with body mass index (BMI) <30 and >30, respectively. Polysaccharide hemostatic agent (PHA; 3 g) was applied topically to the right knees of each patient intraoperatively. The left knees were used as controls. A negative suction drain was used and the effect of PHA and BMI on postoperative bleeding was evaluated. RESULTS: Blood loss was significantly higher (p = 0.027, r = 0.397) for patients with higher BMI. Treatment by local application of PHA to potential bleeding sites significantly reduced blood loss-314 ± 151 ml (50-600) for the right knees versus 468 ± 140 ml (150-700) for the left knees (p = 0.007) in group 1; 420 ± 251 ml (100-900) for the right knees versus 620 ± 229 ml (350-1125) for the left knees (p = 0.036) in group 2. Blood loss reduction between the right and left knees was no different between the two groups (p = 0.173). CONCLUSIONS: By reducing blood loss and the need for postoperative blood transfusion in patients with high BMI, PHA can be of value as adjuvant therapy in new blood-management procedures in major joint-replacement surgery.