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Molecular interactions between zoledronic acid and bone: an in vitro Raman microspectroscopic study

Juillard, Audrey and Falgayrac, Guillaume and Cortet, Bernard and Vieillard, Marie-Hélène and Azaroual, Nathalie and Hornez, Jean-Christophe and Penel, Guillaume and Gasser, Juerg Andreas (2010) Molecular interactions between zoledronic acid and bone: an in vitro Raman microspectroscopic study. Bone, 25. ISSN 8756-3282

Abstract

Abstract
The aim of this study was to investigate molecular interactions between a bisphosphonate (BP), zoledronic acid, and bone tissue by the use of Raman microspectroscopy. In this way, samples of hydroxyapatite (HA), as a bone model, and Wistar rat femurs were soaking in zoledronic acid solutions. Sample surfaces were studied by Environmental Scanning Electron Microscopy and Raman spectroscopy. The amount of zoledronic acid incorporated onto the samples was determined by 31P NMR spectroscopy. After impregnation new Raman bands with frequencies close to characteristic peaks of zoledronic acid (in particular phosphate moieties and imidazole ring of the R2 side-chain) were observed on the both types of samples. Physico-chemical parameters of bone were significantly modified (P<0.0001). The mineral to organic ratio and the carbonate to phosphate ratio were decreased and the crystallinity was increased. Released inorganic phosphate was detected in the solutions by 31P NMR spectroscopy. The Raman shift of the bands corresponding to the phosphate groups and the imidazole ring of the BP highlight their implication in the binding to the mineral. The detection of released inorganic phosphate in solutions, the modifications of the mineral to phosphate ratio and the carbonate to phosphate ratio demonstrate the existence of ionic substitutions in the lattice secondary to BP binding, and especially at CO32- type-B and PO43- sites. The increase of the crystallinity is in favour of a re-organisation of the lattice with a higher symmetry. The use of Raman spectrometry brings new and complementary information on the impact of zoledronic acid on the bone composition at a molecular level.

Item Type: Article
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Additional Information: Archiving not allowed on institutional repository
Keywords: Bone; Hydroxyapatite; Raman microspectroscopy; Zoledronic acid; Molecular interactions Molecular interactions
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/1944

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