The aim of this 2-year longitudinal observational study was to explore hand bone loss as a disease outcome measure in established rheumatoid arthritis (RA). A cohort of 215 patients with RA (170 women and 45 men, aged 20-70 years) were recruited from the Oslo RA registry and studied for changes in hand bone mass during a 2-year follow-up. Digital X-ray radiogrammetry (DXR) was used to measure cortical hand bone mineral density (BMD) and metacarpal cortical index, whereas dual-energy X-ray absorptiometry (DXA) was used to assess whole hand BMD, which measures total cortical and trabecular bone. DXA-BMD total hip and spine and informative data for disease and therapy were also collected. Hand bone loss could be revealed over a 2-year follow-up measured by DXR-BMD (-0.90%, P < 0.01), but not by DXA-BMD (0.00%, P = 0.87). DXA-BMD hand bone loss was only observed in patients with disease duration < or = 3 years and not in patients with longer disease duration (-0.96% versus 0.24%, P < 0.01), whereas loss of DXR-BMD was independent of disease duration. Disease activity (measured by the disease activity score including 28 joints) independently predicted loss of DXR-BMD but not changes in the DXA-BMD hand in the multivariate analysis. The change in DXR metacarpal cortical index was highly correlated to DXR-BMD (r = 0.94, P < 0.001). These data suggest that DXR-BMD may be a more appropriate technique to identify RA-related bone involvement in hands compared with DXA-BMD measurement, but further studies are needed to explore this hypothesis.