Alendronate and omeprazole have been found to influence bone healing by interfering with osteoclastic activity, resulting in increased bone formation. The biological effect of these conventional drugs, incorporated into bioactive bone cement (G2B1), was investigated in a rabbit model. The 2 materials and a control were inserted in defects created in the femoral condyle of rabbits. Implantation time was 6 and 12 weeks. After retrieval, micro-computed tomography and histomorphometry were performed to quantify bone mineral density (BMD) and bone volume (BV) of the implant-surrounding bone mass and the percentage of bone-to-implant contact. BMD and BV were similar in all groups. The percentage of bone-to-implant contact was significantly lower in the alendronate and omeprazole groups than in controls after 6 weeks of implantation. After 12 weeks, this difference in bone contact disappeared for the omeprazole but not for the alendronate implants, which were almost completely surrounded by a fibrous capsule, associated with a limited inflammatory response. In conclusion, in the current study, alendronate and omeprazole did not result in better bone healing when incorporated into bioactive bone cement than did plain control implants. Moreover, an additional cytotoxicity assay revealed that alendronate evoked a toxic response.