Recently, osteoclast-mediated resorption of calcium phosphate cement (CPC) was inhibited in vivo, by pre-loading them with a V-Type proton-ATPase pump inhibitor bafilomycin A1. An increase in peri-implant bone formation was also noted. However, bafilomycin is not clinically regulated and thus members of a class of regulated P-Type proton/potassium-ATPase inhibitors, specifically omeprazole and pantoprazole were examined. Increasing doses of these drugs were loaded into CPCs and implanted into femoral defects in rats. The response was examined histologically and by computer tomography for bone resorption and formation activity at the implant site. Pre-loading omeprazole and pantoprazole into CPCs inhibited osteoclast-mediated resorption of the implant, but no concurrent increase in peri-implant bone was observed at any of the doses tested. Overall, pre-loading this class of regulated drugs to inhibit resorption of CPC implants may provide a simple strategy to delay implant degradation in a clinical setting.