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Increased strontium uptake in trabecular bone of ovariectomized calcium‐deficient rats treated with strontium ranelate or strontium chloride
Authors:Bernhard Pemmer  Jochen G Hofstaetter  Florian Meirer  Stephan Smolek  Peter Wobrauschek  Rolf Simon  Robyn K Fuchs  Matthew R Allen  Keith W Condon  Susan Reinwald  Roger J Phipps  David B Burr  Eleftherios P Paschalis  Klaus Klaushofer  Christina Streli  Paul Roschger
Abstract:Based on clinical trials showing the efficacy to reduce vertebral and non‐vertebral fractures, strontium ranelate (SrR) has been approved in several countries for the treatment of postmenopausal osteoporosis. Hence, it is of special clinical interest to elucidate how the Sr uptake is influenced by dietary Ca deficiency as well as by the formula of Sr administration, SrR versus strontium chloride (SrCl2). Three‐month‐old ovariectomized rats were treated for 90 days with doses of 25 mg kg?1 d?1 and 150 mg kg?1 d?1 of SrR or SrCl2 at low (0.1% Ca) or normal (1.19% Ca) Ca diet. Vertebral bone tissue was analysed by confocal synchrotron‐radiation‐induced micro X‐ray fluorescence and by backscattered electron imaging. Principal component analysis and k‐means clustering of the acquired elemental maps of Ca and Sr revealed that the newly formed bone exhibited the highest Sr fractions and that low Ca diet increased the Sr uptake by a factor of three to four. Furthermore, Sr uptake in bone of the SrCl2‐treated animals was generally lower compared with SrR. The study clearly shows that inadequate nutritional calcium intake significantly increases uptake of Sr in serum as well as in trabecular bone matrix. This indicates that nutritional calcium intake as well as serum Ca levels are important regulators of any Sr treatment.
Keywords:strontium ranelate  strontium chloride  dietary calcium  ovariectomized rats  SR µ  ‐XRF  qBEI  elemental mapping  principal component analysis  k‐means clustering
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