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BACKGROUND: Joint immobilisation improves the therapeutic effect of intra-articular glucocorticoid injection for knee synovitis. This may be due to retarded steroid resorption by immobilisation, a procedure that also could influence cartilage and bone metabolism. OBJECTIVE: To evaluate changes in cartilage and bone turnover after intra-articular glucocorticoid treatment for knee synovitis with and without postinjection rest. METHODS: 20 patients with rheumatoid arthritis and knee synovitis were randomised to 24 hour bed rest or to normal activity after intra-articular glucocorticoid treatment. Serum and urine markers of cartilage and bone turnover were studied for two weeks. Cartilage oligomeric matrix protein (COMP) was used as a marker of cartilage turnover, osteocalcin as marker of bone formation, and deoxipyridinoline (DPD) as marker of bone resorption. RESULTS: After the glucocorticoid injection COMP levels decreased in both groups (p<0.001), but significantly more in resting patients. Serum osteocalcin levels decreased significantly (p<0.001) without any difference between the groups. DPD was unchanged in both groups. CONCLUSIONS: Intra-articular glucocorticoid treatment for knee synovitis reduced serum COMP, which suggests that such treatment may have a cartilage protective effect. The slightly larger decrease of serum COMP in the resting group may reflect a lower clearance of COMP from the joint cavity. Serum osteocalcin was temporarily reduced, indicating a reversible suppression of bone formation.