RESUMEN
The aim of the current work was to study the physico-chemical interactions of a bisphosphonate molecule, risedronate, with a well-characterised synthetic nanocrystalline apatite (NCA) as a model bone mineral. We adopted a global approach, using complementary physico-chemical techniques such as FTIR, RAMAN and NMR spectroscopies in order to learn more about the interaction process of risedronate with the apatitic surface. The results obtained suggest that risedronate adsorption corresponds to an ion substitution reaction with phosphate ions occurring at the crystal surface. This mechanism explains the greater amount adsorbed (N) for NCA, compared to well crystallised stoichiometric hydroxyapatite, attributable to the well-developed hydrated layer at the surface of the nanocrystals. However, most calcium ions remain attached to the solid phase and the formation of insoluble risedronate calcium salts must also be considered as a competitive reaction to the adsorption. Thus a calcium risedronate salt was synthesised and fully characterised for comparison to the solids after adsorption. Following spectroscopic results, it can be concluded that a strong interaction was established between risedronate ions and calcium ions at the apatitic surface. However, under these experimental conditions there is no nucleation of a distinct calcium risedronate salt and the apatite crystals retain their integrity.
Asunto(s)
Apatitas/química , Ácido Etidrónico/análogos & derivados , Nanopartículas/química , Ácido Etidrónico/química , Espectroscopía de Resonancia Magnética , Ácido Risedrónico , Espectrometría RamanRESUMEN
Bisphosphonates, potent inhibitors of bone resorption, have been used clinically to correct the continued loss of bone mass in osteoporosis and in other conditions. However, there has been some concern that long-term treatment with these compounds, as well as more recently developed drugs, may also decrease the rate of bone formation. Bisphosphonates, which are strongly bound to hydroxyapatite crystals, may alter the structure and reactivity of the crystals, interfere with new crystal nucleation and growth, as well as alter the short-range order of newly formed crystals. We have investigated the chemistry and structure of the solid calcium-phosphate mineral phase of lumbar vertebrae of ovariectomized, 6.5-month-old rats treated with bisphosphonates for 1 year after onset of osteopenia. Appropriate control groups were used for comparison. The techniques used to assess the mineral phase were chemical analyses, Fourier transform-infrared (FT-IR) and FT-Raman spectroscopy, FT-IR microspectroscopy, and phosphorus-31 magic-angle-sample spinning nuclear magnetic resonance spectroscopy ((31)P MAS NMR). The (31)P MAS NMR spectra of trabecular bone of lumbar vertebrae of control, ovariectomized, and treated animals were similar. However, there were several significant differences in the results obtained by FT-IR spectroscopy of the whole tissue samples, FT-IR microspectroscopy of sections of bone, and chemical analyses. For example, whereas chemical analyses demonstrated that the CO(3) content of the mineral phase of the ovariectomized animals was decreased compared with controls, FT-IR microspectroscopy of bone sections showed no changes in the relative CO(3) content, but some changes in the environment of the CO(3) groups. However, chemical analyses of the crystals, combined with data from all three spectroscopic methods and with data from serum analysis, did indicate small changes in the mineral phase after ovariectomy, corrected after treatment with bisphosphonates. In any event, the chemical and structural data in the present studies demonstrate that the bisphosphonate, tiludronate, does not significantly alter the mineral components of bone after 1 year of treatment during the course of which bone loss was reversed.