About Zoledronic acid Third-generation bisphosphonate, Osteoclastic bone resorption inhibitor(Calcium regulator). Mechanism of Action of Zoledronic acid Zoledronate is a third generation bisphosphonate. It is an analogue of pyrophosphate in which the P-O-P bond is replaced by a non hydrolysable P-C-P bond. With divalent cation such as Ca2+ (calcium ion) in the bone, they can capable to form chelating complex and form a three dimensional structure. It has high affinity for active remodeling site in the bone. Bisphosphonate retard formation and dissolution of hydroxy apatite crystals within bone and other site. Bisphosphonate remain in the matrix until the bone is remolded and then released in the acid environment of the resorption lacunae beneath the osteoclasts as the overlying mineral matrix is dissolved. It produces antiresorptive action by osteoclasts apoptosis activity and by inhibition of components of the cholesterol biosynthetic pathway.