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

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

Differential accumulation of lead and zinc in double-tidemarks of articular cartilage

The trace elements Lead (Pb) and Zinc (Zn) are of great biological impact. Long-term exposure to increased Pb concentrations is associated with several chronic diseases whereas Zn is essential for numerous enzymes. In a recent study we found remarkably elevated concentrations of Pb and Zn in the tidemark (TM), which is a mineralization front of human articular cartilage. Duplication or multiplication of TMs occurs with advancing age or degeneration. We hypothesized that trace elements accumulate in TMs as a function of time. Thus, in cases of double TMs, the inner (older) TM should have higher Pb and Zn levels than the outer (younger) TM. Undecalcified tissue from articular cartilage and subchondral bone of femoral heads and patellae was examined by synchrotron radiation induced confocal micro X-ray fluorescence analysis (SR µ-XRF) and by quantitative backscattered electron imaging to determine the local distribution of Ca, Zn and Pb in this tissue. The evaluation of x-ray fluoresence intensities in double TMs revealed in average a 2.6 fold higher Pb-level in the inner TM compared to the outer TM while the Zn concentrations were simmilar. The biochemical composition of the TM seems to selectively accumulate Pb from the interstitial fluid of articular cartilage. In contrast, Zn is supposed to be a fixed constituent of the TM. The results might be of clinical importance, when during degenerative processes in osteoarthritis the tidemark region is destroyed and remarkable concentrations of Pb (up to the 62 fold of the bone level) are released into the body fluid

Increased zinc accumulation in mineralized osteosarcoma tissue measured by confocal synchrotron radiation micro X-ray fluorescence analysis

Abnormal tissue levels of certain trace elements such as zinc (Zn) were reported in various types of cancer. Little is known about the role of Zn in osteosarcoma. Using confocal synchrotron radiation micro X-ray fluorescence analysis, we characterized the spatial distribution of Zn in high-grade sclerosing osteosarcoma of nine patients (four women/five men; seven knee/one humerus/one femur) following chemotherapy and wide surgical resection. Levels were compared with adjacent normal tissue. Quantitative backscattered electron imaging as well as histological examinations was also performed. On average, the ratio of medians of Zn count rates (normalized to calcium) in mineralized tumor tissue was about six times higher than in normal tissue. There was no difference in Zn levels between tumor fraction areas with a low fraction and a high fraction of mineralized tissue, which were clearly depicted using quantitative backscattered electron imaging. Moreover, we found no correlation between the Zn values and the type of tumor regression according to the Salzer-Kuntschik grading. The underlying mechanism of Zn accumulation remains unclear. Given the emerging data on the role of trace elements in other types of cancer, our novel results warrant further studies on the role of trace elements in bone cancer. Copyright © 2016 The Authors. X-Ray Spectrometry published by John Wiley & Sons Ltd