OBJECTIVE To analyze clinical, radiological, and drug (disease modifying antirheumatic drug, DMARD) dependent factors influencing bone turnover in patients with rheumatoid arthritis (RA). METHODS We investigated in a one-year double blind randomized study comparing intramuscular (im) gold with im methotrexate (MTX), whether the variation of inflammatory activity or functional capacity, the ascending anatomic stage, or DMARD treatments have an influence on bone formation (osteocalcin) in patients with RA. RESULTS Patients (n = 48) enrolled at the beginning of our study had significantly increased osteocalcin levels (3.45 +/- 0.93-->4.42 +/- 1.39 ng/ml p < 0.02) after one year if inflammatory activity decreased (> or = 1 SD: erythrocyte sedimentation rate (ESR) 26.4 mm/h, C-reactive protein (CRP) 3.8 mg/dl). We found a significant negative correlation of the one-year CRP- (r = -0.44, p < 0.001) or ESR differences (r = -0.45, p < 0.001) with the corresponding osteocalcin differences. This was also evident if these patients were pooled with 15 patients excluded from the double blind study as already receiving DMARD treatment (n = 63; p < 0.01). Patients with impaired functional capacity also had significantly reduced osteocalcin levels (p < 0.01). In both cases, alkaline phosphatase showed no significant differences. CONCLUSIONS Our data suggest that osteocalcin, a useful followup variable of bone turnover, is changed significantly (p < 0.02) in patients with RA regarding inflammatory activity and functional capacity. In contrast to alkaline phosphatase, a fall in inflammatory activity stimulated and impairment of functional capacity significantly decreased osteocalcin levels in patients with RA.