Changes in biochemical markers of joint tissue metabolism in a randomized controlled trial of glucocorticoid in early rheumatoid arthritis

OBJECTIVE: To determine the effects of low-dose prednisolone on joint tissue metabolism in early rheumatoid arthritis (RA). METHODS: In addition to a range of biochemical markers of cartilage, bone and synovial tissue turnover, levels of pro-matrix metalloproteinase 3 (pro-MMP-3), pro-MMP-1, and cytidine deaminase (CD) were measured in serum from 79 of 128 patients with early RA who took part in the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study. Serum concentrations of joint tissue metabolites on treatment and off treatment were compared using Student's t-test. RESULTS: Levels of the keratan sulfate epitope, 5D4, and glycosaminoglycan (GAG) were similar on and off treatment. However, the levels of synovium-derived markers, hyaluronate (HA) and N-propeptide of type III procollagen (PIIINP), were reduced by 23.9% (P < 0.01) and 25.2% (P < 0.001), respectively, during treatment with prednisolone. Serum osteocalcin (OC) was reduced by 25.8% (P < 0.001), while the levels of CD and pro-MMP-3 increased by 31.2% (P < 0.01) and 53.7% (P < 0.001) during prednisolone treatment compared with the off-treatment period. CONCLUSION: Low-dose prednisolone had no significant effect on markers of cartilage turnover (GAG, 5D4) in early RA, suggesting that early erosions do not involve cartilage surfaces. The reduction in the markers of bone turnover (OC) and synovial tissue turnover (HA and PIIINP) support the general view that prednisolone reduces synovitis and suppresses bone turnover.