OBJECTIVE Zoledronic acid (ZA), a new-generation intravenous bisphosphonate, exhibits the greatest affinity for bone mineral with the longest retention, thereby leading to its ability to be dosed at annual intervals in the treatment of osteoporosis. The purpose of this preliminary study was to evaluate the effects of systemic administration of a single dose of ZA on osseointegration and bone healing around titanium dental implants. METHODS Thirty-six female New Zealand rabbits (aged 6-12 months) were used in this study. Rabbits were randomly assigned to 1 of 3 groups: sham control group (SH), ovariectomy group (OVX), and OVX and ZA group (OVX + ZA). Animals in the OVX and OVX + ZA groups were subjected to bilateral ovariectomy, whereas animals in the SH group were sham operated. Eight weeks later, 1 implant was placed in each tibia of the animals. ZA was administered in the OVX + ZA group during the implantation, whereas the OVX and SH groups received saline solution infusions. All of the subjects were sacrificed 8 weeks after the implantation, and tibial specimens were harvested. Histomorphometric bone-to-implant contact analysis, resonance frequency analysis, removal torque testing, and digital radiographic absorptiometry were administered, and the data were statistically analyzed. RESULTS Histomorphometric, resonance frequency, and radiodensitometric analyses showed significant improvement in osseointegration of implants in the OVX + ZA group compared with the OVX group. However, the differences in removal torque results between the groups were not statistically significant. CONCLUSIONS The results of this study suggest that systemic ZA administration may improve osseointegration of titanium implants placed in estrogen-deficient states of bone.