Increased strontium uptake in trabecular bone of ovariectomized calcium-deficient rats treated with strontium ranelate or strontium chloride

Abstract

Based on clinical trials showing the efficacy to reduce vertebral and nonvertebral 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 (SrCl 2 ). Three-month-old ovariectomized rats were treated for 90 days with doses of 25 mg kg À1 d À1 and 150 mg kg À1 d À1 of SrR or SrCl 2 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 SrCl 2 -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.

Confocal micro-x-ray fluorescence spectrometer for light element analysis

“…21 Details regarding the data treatment can also be found in Ref. 20. For both setups, in the laboratory and at the synchrotron, about 2.7-fold increased Sr uptake into newly formed bone was found in case of Ca deficiency (see Fig.…”

“…For more detailed information see cited paper. 20 Figure 11 shows a comparison of obtained Ca and Sr maps of the same sample area with a quantitative backscattered electron image (qBEI) on the right. The maps show that both measurements (SR and lab micro-XRF) are comparable.…”

“…Also, the SR peak is much higher than in the laboratory spectrum. For further validation of the lab spectrometer the maps of the two samples (normal and deficient Ca diet with SrCl 2 treatment) measured in the lab spectrometer were evaluated the same way as the maps obtained within a previous study 20 at the synchrotron, using principal component analysis and kmeans clustering. 21 Details regarding the data treatment can also be found in Ref.…”

“…20 The two samples were L3 vertebra bone sections (sagittal cutted) from three-month-old OVX Sprague-Dawley rats that have been treated with SrCl 2 (56 mg/kg/d). Furthermore, the rats were fed with different amounts of dietary Ca, normal (1.19 wt.…”

Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation

“…21,22 Sr upregulates osteoblast-related gene expression and alkaline phosphatase activity of mesenchymal stem cells, and also inhibits the differentiation of osteoclasts. 23 As a result, Sr has good potential in the treatment of osteoporosis.…”