title: Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro.
abstract: Bisphosphonates (BPs), which display a high affinity for calcium phosphate surfaces, are able to selectively target bone mineral, where they are potent inhibitors of osteoclast-mediated bone resorption. The dissolution of synthetic hydroxyapatite (HAP) has been used previously as a model for BP effects on natural bone mineral. The present work examines the influence of BPs on carbonated apatite (CAP), which mimics natural bone more closely than does HAP. Constant composition dissolution experiments were performed at pH 5.50, physiological ionic strength (0.15M) and temperature (37 degrees C). Selected BPs were added at (0.5 x 10(-6)) to (50.0 x 10(-6))M, and adsorption affinity constants, K(L), were calculated from the kinetics data. The BPs showed concentration-dependent inhibition of CAP dissolution, with significant differences in rank order zoledronate > alendronate > risedronate. In contrast, for HAP dissolution at pH 5.50, the differences between the individual BPs were considerably smaller. The extent of CAP dissolution was also dependent on the relative undersaturation, sigma, and CAP dissolution rates increased with increasing carbonate content. These results demonstrate the importance of the presence of carbonate in mediating the dissolution of CAP, and the possible involvement of bone mineral carbonate in observed differences in bone affinities of BPs in clinical use.
authors: Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA. zh2@buffalo.edu
authors: Zachary J
authors: ZJ
authors: Henneman
authors: George H
authors: GH
authors: Nancollas
authors: F Hal
authors: FH
authors: Ebetino
authors: R Graham G
authors: RG
authors: Russell
authors: Roger J
authors: RJ
authors: Phipps
mesh_terms: D001031:Apatites / Q000378:metabolism*; D018786:Bone Substitutes / Q000378:metabolism; D004164:Diphosphonates / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D000077211:Zoledronic Acid
chemical_list: D001031:Apatites; D018786:Bone Substitutes; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid