Tiludronate (Tiludronic Acid) disodium hemihydrate is an orally active bisphosphonate compound used primarily in metabolic bone disorder research. It functions as an osteoregulator and acts as a potent inhibitor of the osteoclast vacuolar H+ -ATPase, possessing antiresorptive and anti-inflammatory properties [4].

Tiludronate exhibits significantly enhanced potency in inhibiting proton transport, with a five-fold greater efficacy in kidney-derived vesicles (IC 50 =1.1 mM) and an even more pronounced, ten-thousand-fold increase in vesicles sourced from osteoclasts (IC 50 =466 nM). Additionally, it effectively inhibits proton transport in yeast microsomal preparations (IC 50 =3.5 microM) and disrupts the function of purified yeast V-ATPase. Notably, Tiludronate's inhibition of proton transport mediated by osteoclast V-ATPase is characterized by its rapid onset, pH-dependence, and reversibility[3].

Tiludronate exhibits a dose-dependent inhibitory effect on bone resorption, primarily by diminishing the mature osteoclasts' ability to secrete protons into the resorption space and promoting their detachment from the bone matrix. Furthermore, Tiludronate has been evaluated in various osteoporosis models, notably preventing the reduction in skeletal mass in the castrated male rat model (doses ranging from 5-200 mg/kg; orally). This prevention was confirmed through physical assessments of bone weight and density, as well as chemical analyses of calcium and phosphate content[3].