Serum hyaluronic acid as a potential marker with a predictive value for further radiographic progression of hand osteoarthritis

SummaryObjectiveTo compare serum levels of hyaluronic acid (HA) between patients with erosive and non-erosive hand osteoarthritis (HOA), and investigate its association with morphological changes and radiographic progression over 2 years.MethodsFifty-five women with erosive and 33 women with non-erosive HOA were included in this study. All underwent clinical examination, which included assessment of pain, swelling, deformity and deviation of small hand joints and completed health assessment questionnaires. Serum levels of HA were measured by ELISA. Three-phase bone scintigraphy was performed at baseline. Radiographs of both hands were performed at baseline and after 2 years and scored according Kallman grading scale.ResultsSerum levels of HA were significantly higher in patients with erosive than with non-erosive HOA (P<0.01). It correlated significantly with the number of hand joints with deviations and deformities. HA adjusted for age and disease duration significantly correlated with radiographs at baseline and after 2 years in all patients with HOA (r=0.560 and r=0.542, P<0.01 for both correlations). Although there was an association between HA and radiographic score in erosive disease, after adjustment for confounders it remained no longer significant. HA adjusted for confounders correlated significantly with the late phase in all patients with HOA (r=0.412, P<0.01) and in patients with erosive disease (r=0.320, P<0.05).ConclusionHA is increased in patients with erosive HOA and could be proposed as a surrogate marker with a predictive value for further radiographic progression of HOA in general. Further investigation is necessary to confirm these results

A 5-year randomized controlled, double-blind study of glycosaminoglycan polysulphuric acid complex (Rumalon®) as a structure modifying therapy in osteoarthritis of the hip and knee

Objective To determine the structure (disease) modifying effect of a glycosaminoglycan polypeptide association complex (GP-C; Rumalon®) in patients with knee and hip osteoarthritis (OA). Methods Double-blind, randomized, placebo-controlled five-year study. Primary assessment criterion was change in radiographic joint space width between baseline and follow-up at 5 years. Secondary outcome criteria included Lequesne algofunctional index (LAI), pain on passive motion and consumption of non-steroidal antiinflammatory drugs (NSAIDs). The patients received 10 courses of injections of placebo or GP-C 2ml intramuscularly in 5 years (two courses each year). Each course included 15 injections administered twice weekly. Results There were 277 patients with knee OA and 117 patients with hip OA. Control and GP-C treated groups were comparable as to sex, age, duration of disease, body weight, X-ray stage and value of LAI at the baseline. Knee joint space at 5 years decreased 0.37±0.08 (mean±standard deviation) mm for GP-C and 0.42±0.08mm for placebo groups (P=0.68). Hip joint space at 5 years decreased 0.21±0.08mm for GP-C and 0.22±0.08mm for placebo groups (P=0.53). In a subset of patients with hip OA, Kellgren–Lawrence≥2 and JSW≥1mm, there was a trend in favor of GPC for lower joint space narrowing in 5 years (P=0.11). In addition, there were no statistical differences between the treatment groups in LAI, pain on passive motion and consumption of NSAIDs. Side-effects after GP-C (14.5%) were rare, mild and not more frequent than in the placebo group (15%). Conclusion We were not able to demonstrate a structure modifying effect of GP-C in OA of the hip or knee. Radiographic progression of OA in both knee and hip OA was lower than expected in both study groups

Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis

AbstractStudy objectives: To study prognostic value of different biochemical markers for morphological progression of early knee osteoarthritis.Design: A total of 89 patients with knee osteoarthritis (OA) were enroled into the study. The follow-up period was 2 years. Radiological OA progression was evaluated by measuring joint space width. Pentosidine was detected using the HPLC method described earlier, cartilage oligomeric matrix protein (COMP) using the method published by our team. MMP-9, tissue inhibitors of metalloproteinases (TIMP), YKL-40 and hyaluronic acid were detected using commercially available kits.Results: In the group of patients suffering from knee OA, higher serum levels of pentosidine (P=0.04), MMP-9 (P=0.02), TIMP (P=0.04) and COMP (P=0.05) were detected compared with healthy control subjects. Using a correlation analysis method, it has been found that the patients with higher basic serum levels of hyaluronic acid had a faster radiological progression (r=0.56, P<0.005), as well as the patients with higher basic serum pentosidine levels (r=0.30, P<0.005). Other biochemical markers had no statistically significant prognostic value.Conclusions: In our study, serum levels of hyaluronic acid and pentosidine had a predictive value for further development of knee OA in that further joint space narrowing was detected in the patients with knee OA in the next 2 years

Total Joint Replacement after Glucosamine Sulphate Treatment in Knee Osteoarthritis: Results of a Mean 8-Year Observation of Patients from Two Previous 3-Year, Randomised, Placebo-Controlled Trials

OBJECTIVE: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo. METHODS: Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement. RESULTS: Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up). Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P=0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20-0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log-Rank test survival analysis confirmed a significantly decreased (P=0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate. A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up. CONCLUSIONS: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation