Assessment of disease activity in Rheumatoid Arthritis using urinary CTx-I levels as a marker of bone destruction and serum IL-6 as a marker of inflammation.

摘要

Background and Objectives: Urinary C-terminal cross linking telopeptide of type 1 collagen (CTX-I) is a specific marker of bone resorption.Also, IL-6 in the synovial cavity may contribute to that in the serum and may raise its levels. The aim of this study was to measure urinary CTx-I and serum interleukin-6(IL-6) levels in rheumatoid arthritis (RA) patients and to use these markers to assess the disease activity by comparing them with the existing markers of disease activity. Methods: 35 RA patients, 18 patients suffering from osteoarthritis (OA) with / without inflammatory synovitis and 18 age - matched healthy controls were included in the study. Urinary CTx-I and serum IL-6 levels were measured in all of them.Results: A total of 71 subjects were included in the study. A positive correlation was found between CTx-I and age (p = 0.044, r = 0.362), DAS28 (p = 0.007, r = 0.451), swollen joint count (p = 0.006, r = 0.452) and tender joint count (p = 0.006, r = 0.453).Levels did not correlate with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor and disease duration. IL-6 levels were found to have significant associations with age (p = 0.012, r = 0.42), CRP (p = 0.048, r = 0.337), DAS28 (p = 0.024, r = 0.382), swollen joint count (p = 0.001, r = 0.555) and tender joint count (p = 0.04, r = 0.349). No correlations were found between IL-6 and ESR, Rheumatoid factor and disease duration. A positive correlation was also seen between CTx-I and IL-6 (p = 0.03, r = 0.352).Conclusions: Serum IL-6 and urinary CTx-I levels are markedly elevated in RA with active disease and their increased levels correlate with the existing markers of increased disease activity. Introduction Rheumatoid Arthritis (RA) is a chronic multisystem disease of unknown etiology. It is characterized by persistent inflammatory synovitis, usually involving multiple joints in a symmetrical distribution. The potential of the synovial inflammation to cause cartilage and bone erosions and subsequent changes in joint integrity is the hallmark of the disease.1 The overall prevalence of RA is around 1 % in the general population.2 India harbors around 5.4 % of the global burden of RA.3 Osteoclastic activation has been suggested to be the dominant process leading to bone resorption in Rheumatoid arthritis (RA). Most biochemical indices of bone resorption are related to collagen breakdown products such as hydroxyproline or the various collagen cross links and telopeptides.4 Of these , urinary C-terminal cross linking telopeptide of type 1 collagen(CTX-I) is a more specific marker of bone derived type 1 collagen fragments in urine in RA.5 Cross linking compounds pyridinoline( PYD) and deoxypyridinoline (DPD) levels in urine have previously been studied to assess collagen degradation6 and disease activity in RA. But CTX- I levels in urine have not been adequately studied. The appearance of pro-inflammatory cytokines in joint tissue/synovial fluid and serum/plasma of patients with arthritic conditions, suggest that they play a pivotal role in the local and systemic inflammatory response. However in many cases it has not been possible to relate known in vitro effects of pro-inflammatory cytokines to clinical and laboratory observations. IL-6 mediates the synthesis of acute phase proteins.7 Many attempts at establishing a correlation between this cytokine and the disease activity in RA have been made but the results obtained were inconsistent. However a recent animal trial on mice with antigen-induced arthritis confirms the important role of IL-6 in the development of disease.8 Also the synovial fluid in rheumatoid arthritis contains substantially increased amounts of IL-6.9 Using cytokine probes, it has been claimed that IL-6 in rheumatic synovial fluid originates from type B synovial lining cells and fibroblasts.1011 This IL-6 in the synovial cavity may contribute to that in the serum and may raise its levels. Thus the present study was conducted