Bone Abstracts

Strontium ranelate is a promising drug used in the treatment of osteoporosis. This drug has a unique dual effect on bone turnover, simultaneously increasing bone formation by osteoblasts (anabolic effect) and decreasing bone resorption by osteoclasts (antiresorptive effect). The goal of this study was to evaluate: i) anabolic effects of strontium ranelate on the formation of bone-like mineralized matrix in osteoblast cell cultures and ii) changes the drug could cause on the matrix and mineral substance. After 28 days of culture, treatment with strontium ranelate at 0.5 mM Sr²⁺ increased the formation of mineralized nodules. Analysis of the intact matrix by attenuated total reflection Fourier transform infrared spectroscopy showed that the overall bone-like nature of the nodules was preserved, comprising a poorly crystalline, carbonate-containing apatite and a collagenous matrix. We found, however, using synchrotron micro X-ray fluorescence, that strontium was incorporated into the matrix produced under treatment in a dose-dependent manner. In order to further evaluate effects of the drug on the mineral substance, we isolated the minerals and analyzed them by using: Fourier transform infrared spectroscopy, solid-state ¹H nuclear magnetic resonance, micro-Raman spectroscopy, X-ray diffraction, and energy dispersive X-ray spectroscopy. Although all minerals presented typical bone-like features, the mineral produced under 0.5 mM Sr²⁺ showed an increase in the relative type-B carbonate content and in the structural disorder around phosphate sites. We also found that strontium was incorporated into this mineral by replacing slightly less than 10% of calcium in the apatite crystal lattice, which led to an increase in both lattice parameters a and c. In conclusion, strontium ranelate had a clear anabolic effect on the formation of mineralized nodules in osteoblast cell cultures while preserving their overall bone-like nature. We found, however, that treatment changed the composition and crystal structure of the mineral substance.