Bisphosphonates (BPs) are well established as successful antiresorptive agents for the prevention and treatment of bone diseases such as osteoporosis and Paget's disease. The aim of this work was to clarify the reaction mechanisms between a BP molecule, tiludronate, and the nanocrystalline apatite surface. The adsorption of tiludronate on well-characterized synthetic biomimetic nanocrystalline apatites with homogeneous but different compositions and surface characteristics was investigated to determine the effect of the nanocrystalline apatite substrate on the adsorption behavior. The results show that the adsorption of tiludronate on nanocrystalline biomimetic apatite surfaces varies over a large range. The most immature apatitic samples exhibited the highest affinity and the greatest amount adsorbed at saturation. Maturation of the nanocrystals induces a decrease of these values. The amount of phosphate ion released per adsorbed BP molecule varied, depending on the nanocrystalline substrate considered. The adsorption mechanism, although associated with a release of phosphate ions, cannot be considered as a simple ion exchange process involving one or two phosphate ions on the surface. A two-step process is proposed consisting of a surface binding of BP groups to calcium ions associated with a proton release inducing the protonation of surface orthophosphate ions and their eventual solubilization.