title: Structural requirements for bisphosphonate binding on hydroxyapatite: NMR study of bisphosphonate partial esters.
abstract: Eighteen different bisphosphonates, including four clinically used bisphosphonate acids and their phosphoesters, were studied to evaluate how the bisphosphonate structure affects binding to bone. Bisphosphonates with weak bone affinity, such as clodronate, could not bind to hydroxyapatite after the addition of one ester group. Medronate retained its ability to bind after the addition of one ester group, and hydroxy-bisphosphonates could bind even after the addition of two ester groups. Thus, several bisphosphonate esters are clearly bone binding compounds. The following conclusions about bisphosphonate binding emerge: (1) a hydroxyl group in the geminal carbon takes part in the binding process and increases the bisphosphonate's ability to bind to bone; (2) the bisphosphonate's ability to bind decreases when the amount of ester groups increases; and (3) the location of the ester groups affects the bisphosphonate's binding ability.
authors.affiliation: School of Pharmacy, University of Eastern Finland , Biocenter Kuopio, PL-1627, 70210 Kuopio, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Puljula
authors.affiliation: School of Pharmacy, University of Eastern Finland , Biocenter Kuopio, PL-1627, 70210 Kuopio, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Turhanen
authors.affiliation: School of Pharmacy, University of Eastern Finland , Biocenter Kuopio, PL-1627, 70210 Kuopio, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Vepsäläinen
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, CSPBAT, CNRS UMR 7244 , 74, Rue Marcel Cachin, F-93017 Bobigny, France.
authors.forename: Maelle
authors.initials: M
authors.lastname: Monteil
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, CSPBAT, CNRS UMR 7244 , 74, Rue Marcel Cachin, F-93017 Bobigny, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.affiliation: School of Pharmacy, University of Eastern Finland , Biocenter Kuopio, PL-1627, 70210 Kuopio, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Weisell
keywords: Bisphosphonates; alendronate; etidronate; hydroxyapatite; nuclear magnetic resonance