Background A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures.We term this strategy as the "local treatment of osteoporosis".The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement (CPC) as a novel drug delivery system for local treatment of osteoorosis.Methods An in vitro study was performed using CPC fabricated with different concentrations of alendronate (ALE,0,2,5,10 weight percent (wt％)).The microstructure,setting time,infrared spectrum,biomechanics,drug release,and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE.An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups:normal,Sham (ovariectomized (OVX) + Sham),CPC with 2％ ALE,5％ALE,and 10％ ALE groups.At 4 months after the implantation of the composite,animals were sacrificed and the caudal vertebrae (levels 4-7) were harvested for micro-CT examination and biomechanical testing.Results The setting time and strength of CPC was significantly faster and greater than the other groups.The ALE release was sustained over 21 days,and the composite showed good biocompatibility.In micro-CT analysis,compared with the Sham group,there was a significant increase with regard to volumetric bone mineral density (BMD) and trabecular number (Tb.N) in the treated groups (P ＜0.05).Trabecular spacing (Tb.Sp) showed a significant increase in the Sham group compared to other groups (P ＜0.01).However,trabecular thickness (Tb.Th) showed no significant difference among the groups.In biomechanical testing,the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups.Conclusions The ALE-loaded CPC displayed satisfactory properties in vitro,which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.