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.
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.
Schnitzler
Verena
V
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.
Fayon
Franck
F
Despas
Christelle
C
Khairoun
Ibrahim
I
Mellier
Charlotte
C
Rouillon
Thierry
T
Massiot
Dominique
D
Walcarius
Alain
A
Janvier
Pascal
P
Gauthier
Olivier
O
Montavon
Gilles
G
Bouler
Jean-Michel
JM
Bujoli
Bruno
B
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
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