Strontium incorporates at sites critical for bone mineralization in rats with renal failure

We previously demonstrated the development of a mineralization defect during strontium administration and its reversibility after withdrawal in rats with chronic renal failure. Recently, strontium ranelate has been introduced as a therapeutic agent for osteoporosis. However, caution has to be taken, as this bone disorder mainly develops in elderly people who may present a moderately decreased renal function. In order to assess the ultra-structural localization of strontium in bone and thereby to get a better insight into the element's systemic effects on bone, synchrotron-based x-ray micro-fluorescence was applied, which showed that after 2 weeks of strontium loading (2 g l−1 in drinking water) in rats with renal failure, concomitant with the development of impaired mineralization, the element was localized mainly at the outer edge of the mineralized bone, while after longer loading periods, a more homogeneous distribution was found. After washout, strontium was found at sites deeper within the trabeculae, while newly deposited low-strontium-containing mineral was found at the outer edges. Synchrotron x-ray micro-diffraction analysis showed that strontium is incorporated in the apatite crystal lattice through exchange with calcium. The results show that strontium is initially incorporated in bone at sites of active bone mineralization, close to the osteoid/mineralization front. Most likely, strontium binds to matrix proteins serving as crystal nucleation points and by heteroionic substitution with calcium within the hydroxyapatite crystals, thereby impairing further hydroxyapatite formation. After withdrawal, strontium is released from these sites, by which mineralization is restored and the previously formed strontium-containing hydroxyapatite is buried under a new layer of mineralized bone. Copyright © 2006 John Wiley & Sons, Ltd.