New approaches for the local prevention of osteoporotic fractures
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New approaches for the local prevention of osteoporotic fractures P. Janvier1, V. Schnitzler2,6, J.-M. Bouler2, O. Gauthier2, C. Despas3, A. Walcarius3, F. Fayon4, D. Massiot4, G. Montavon5, C. Mellier1 and B. Bujoli1 1
Université de Nantes, CNRS, UMR 6230, CEISAM, UFR Sciences et Techniques, 2 Rue de la Houssinière, B.P. 92208, 44322 Nantes Cedex 3, France. 2 Université de Nantes, INSERM, UMR 791, LIOAD, Faculté de Chirurgie Dentaire, B.P. 84215, 44042 Nantes Cedex 1, France. 3 Nancy-Université, CNRS, UMR 7564, LCPME, 405 Rue de Vandoeuvre, 54600 Villers-lèsNancy, France. 4 CNRS, UPR 3079, CEMHTI, 1D Avenue de la Recherche Scientifique, 45071 Orléans Cedex 02, France. 5 Université de Nantes, SUBATECH, UMR CNRS 6457, Ecole des Mines de Nantes, 4 Rue Alfred Kastler, B.P. 20722, 44307 Nantes Cedex 03, France. 6 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. Keywords: Osteoporosis, biomaterials, calcium phosphate cement ABSTRACT Combining Bisphophonates (BPs) and Calcium Phosphate Cement (CPC) to form a new medical device for the local treatment of Osteoporosis is a promising challenge. Our formulation was optimized from an apatitic-type CPC and we have shown that the best solution consists in introducing the bisphosphonate (Alendronate) in the calcium deficient apatite (CDA), a solid component of the cement, through a chemical exchange reaction. The cement obtained was characterized by 31P NMR and high frequency impedance for monitoring the CPC setting. The presence of Alendronate in the cement was also demonstrated by 31P NMR which has been also used to characterize the chemical transformation of α-TCP (main component of the apatitic cement) during the setting process. BP absorption/desorption experiments have been realized on cement blocks, under continuous flow condition, to model the release profile of the Alendronate. In vivo experiments showed promising results in terms of resorbability of the Alendronate– loaded cement while promoting new bone formation. The same methodology is considered to introduce gallium, a potential inhibitor of osteoclastic resorption, in a CPC formulation. First experiments have shown that gallium can be incorporated in calcium phosphate ceramics (i.e. βTCP) where gallium is part of the network. INTRODUCTION Association between Bisphophonates (BP) and Calcium phosphate Cements (CPC) to form new bone substitutes for the local treatment of Osteoporosis through minimally invasive surgery is a promising challenge. However, the way to introduce BP in a CPC has a critical influence on the setting kinetics. We have found suitable conditions to design the first example of BP-loaded CPC showing appropriate properties including injectability, setting time and drug
release profile [1]. Extension of this work to the case of Gallium, has first been considered by investigating the possibility to incorporate gallium in calcium phosphate ceramics. EXPERIMENTAL DETAILS The formulation was optimized from
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