title: Investigation of alendronate-doped apatitic cements as a potential technology for the prevention of osteoporotic hip fractures: critical influence of the drug introduction mode on the in vitro cement properties.
abstract: Combination of a bisphosphonate (BP) anti-osteoporotic drug, alendronate, with an apatitic calcium phosphate cement does not significantly affect the main properties of the biomaterial, in terms of injectability and setting time, provided that the BP is introduced chemisorbed onto calcium-deficient apatite, one of the components of the cement. In contrast to other modes of introducing the BP into the cement formulation, this mode allows to minimize alendronate release in the cement paste, thus limiting the setting retardant effect of the BP. An original approach based on high frequency impedance measurements is found to be a convenient method for in situ monitoring of the cement setting reaction. The release profile of the drug from a cement block under continuous flow conditions can be well described using a coupled chemistry/transport model, under simulated in vivo conditions. The results show that the released alendronate concentration is expected to be much lower than the cytotoxic concentration.
authors.affiliation: Graftys SARL, Eiffel Park, Bâtiment D, 415 Rue Claude Nicolas Ledoux, Pôle d'Activités d'Aix en Provence, 13854 Aix en Provence Cedex 3, France.
authors.forename: Verena
authors.initials: V
authors.lastname: Schnitzler
authors.forename: Franck
authors.initials: F
authors.lastname: Fayon
authors.forename: Christelle
authors.initials: C
authors.lastname: Despas
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Khairoun
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mellier
authors.forename: Thierry
authors.initials: T
authors.lastname: Rouillon
authors.forename: Dominique
authors.initials: D
authors.lastname: Massiot
authors.forename: Alain
authors.initials: A
authors.lastname: Walcarius
authors.forename: Pascal
authors.initials: P
authors.lastname: Janvier
authors.forename: Olivier
authors.initials: O
authors.lastname: Gauthier
authors.forename: Gilles
authors.initials: G
authors.lastname: Montavon
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bouler
authors.forename: Bruno
authors.initials: B
authors.lastname: Bujoli
mesh_terms: D000327:Adsorption / Q000187:drug effects; D019386:Alendronate / Q000494:pharmacology*; D001031:Apatites / Q000494:pharmacology*; D001843:Bone Cements / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology; D058266:Dielectric Spectroscopy; D004164:Diphosphonates / Q000494:pharmacology; D006620:Hip Fractures / Q000150:complications / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D058866:Osteoporotic Fractures / Q000150:complications / Q000517:prevention & control*; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D001031:Apatites; D001843:Bone Cements; D002130:Calcium Phosphates; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; C018392:tricalcium phosphate; C494366:calcium phosphate, dibasic, dihydrate; D019386:Alendronate