The aim of this study is to develop a simple, convenient and effective approach to synthesize nano-sized hydroxyapatite (nano-HA) at high-scale yield. Nano-HA was wet synthesized in the presence or absence of alendronate sodium (ALN), one of bisphosphonates for anti-osteoporotic. Then aged and washed nano-HA precipitate was directly treated by mechanical activation combined with the chemical dispersion of ALN to prevent the agglomeration of nano-HA. ALN acted not only as a chemical dispersant but also as an orthopedic drug. In vitro release showed that ALN was released slowly from nano-HA. Transmission electron microscopy (TEM) revealed that nano-HA with size less than 100 nm appeared as single particle after being treated by mechanical activation combined with the dispersion of ALN (AMA-HA and MA-HA). High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) confirmed that as-prepared nanoparticles were HA with low crystallinity and crystallite size. Fourier transform infrared spectroscopy (FTIR) indicated that the phosphonate groups in ALN were introduced to bond with the Ca2+ of HA to impede the growth of HA crystal. Zeta potential illustrated that the absolute value of surface negative charge of nano-HA increased significantly with the addition of ALN, which inhibited the agglomeration of nano-HA. The present approach makes it feasible to produce nano-HA at high-scale yield, which provide the possibility to construct bone graft.