The main aim of this study was to determine the effect of zoledronic acid (ZOL) on parameters of dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) in unaffected bones of patients with Paget's disease of bone (PDB). The secondary aim was the association of bone markers and Dickkopf (DKK)-1 with parameters of DXA and QUS. Ten consecutive patients with polyostotic PDB (median age: 63 yr) received a single 5-mg ZOL infusion. The patients were subjected to calcaneal QUS and DXA of both lumbar spine (LS) and femoral neck (FN). Blood samples for serum bone markers and DKK-1 were serially obtained for 12 mo. There was a significant increase in LS (p=0.005) and FN bone mineral density (BMD) (p=0.021) 12 mo after ZOL infusion. QUS parameters remained unaffected throughout the study. A significant correlation between broadband ultrasound attenuation and DKK-1 (p<0.001) and between speed of sound and DKK-1 (p=0.033) at baseline was found, which remained significant after adjustment for gender, age, and body mass index. Our data suggest that a single ZOL infusion significantly increases nonpagetic BMD 12 mo after treatment but has no effect on QUS parameters or DKK-1. Significant correlations were observed between QUS parameters and DKK-1 at baseline.