Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral density (BMD) measurements. The aim of this study was to analyze periarticular BMD in more detail by DXA and quantitative ultrasound (QUS). In a cross-sectional study 23 women aged 30-76 years with early RA, mean disease duration 26 +/- 19 months, and 18 men aged 42-69 years, mean disease duration 24 +/- 25 months, were examined. All patients received antirheumatic therapy. The reference population consisted of 103 age-matched controls (68 females, 35 males) and young healthy controls. BMD measurements were performed using a DXA Expert XL densitometer (Lunar). BMD of the whole-hand and two subregions was determined: two subchondral regions of interest (S.CH.) were set within the trabecular bone, distal to the proximal interphalangeal joints of digits II and III excluding the dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal regions of interest (MCP) were set including the entire MCP joint of these fingers. QUS measurements at the proximal phalanges of digits II-V were performed using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was determined. In comparison with whole-hand BMD measurements, bone loss was pronounced in patients with a disease duration of 18-72 months at the subchondral regions of interest in both genders compared with age-matched controls (women: mean BMD loss S.CH. -23%, p<0.001, whole-hand -16%, p<0.001; men: mean BMD loss S.CH. -19%, p < 0.05, whole-hand -12%, p<0.05). The bone changes were also shown by QUS (women: Ad-SOS values of 1950 +/- 90 m/s in RA vs 2137 +/- 35 m/s in young healthy controls (p <0.005); men AD-SOS 1956 +/- 87 m/s in RA vs 2146 +/- 41 m/s in young healthy controls (p <0.05)). These results show that BMD and Ad-SOS values are significantly lowered in patients with early RA and indicate that periarticular osteoporosis in early RA might possibly be better detected using detailed hand scan analyses.