The development of secondary osteoporosis in rheumatoid arthritis (RA) has recently become well recognized, characterized by demineralization at axial and in particular periarticular peripheral bone sites. Our aim was to evaluate multisite quantitative ultrasound (QUS) compared to digital X-ray radiogrammetry (DXR) by the quantification of cortical bone loss dependent on the severity of RA. Fifty-three patients with verified RA underwent QUS measurements (Sunlight Omnisense 7000) with estimation of the speed of sound (QUS-SOS) at the distal radius and at the phalanx of the third digit. Also, bone mineral density (DXR-BMD) and metacarpal index (DXR-MCI) were estimated on metacarpals II-IV using DXR technology. Additionally, Larsen score and Steinbroker stage were assessed. Disease activity of RA was estimated by disease activity score 28 (DAS 28). For the group with minor disease activity (3.2 <or= DAS <or= 5.1), QUS-SOS (phalanx) showed a significant association to DXR-BMD (R = 0.66) and DXR-MCI (R = 0.52). In the case of accentuated disease activity (DAS > 5.1), QUS-SOS of the radius revealed a significant correlation to DXR-BMD (R = 0.71) and DXR-MCI (R = 0.84), whereas for QUS-SOS (phalanx) no significant association to the DXR parameters was shown. The DXR parameters and, to a lesser extent, the QUS data also demonstrated pronounced declines in the case of accentuated disease activity (DAS > 5.1). Both DXR-BMD (-25.9 %, P < 0.01) and DXR-MCI (-38.6 %, P < 0.01) revealed a notable reduction dependent on the severity of RA. Otherwise, QUS-SOS marginally decreased, with -2.6% (radius) and -3.9% (phalanx). DXR revealed a significant reduction of DXR-BMD as well as DXR-MCI dependent on the severity of RA and surpassed multisite QUS as a promising diagnostic tool.