Effects of strontium on the physicochemical characteristics of hydroxyapatite.

In a previous experimental study using a chronic renal failure rat model, a dose-related multiphasic effect of strontium (Sr) on bone formation was found that could be reproduced in an in vitro set-up using primary rat osteoblasts. The results from the latter study allowed us to distinguish between a reduced nodule formation in the presence of an intact mineralization at low Sr-doses (1 microg/ml) and an interference of the element with the hydroxyapatite (HA) formation at high doses (20-100 microg/ml). To further investigate the latter effect of Sr on physicochemical bone mineral properties, an in vitro study was set up in which the UMR-106 rat osteosarcoma cell line was exposed to Sr, added to the cell culture medium in a concentration range varying between 0-100 microg/ml. Temporal growth and functionality of the culture was investigated by measurement of the alkaline phosphatase activity and calcium (Ca) concentration in the culture medium (used as an index of Ca-incorporation, i.e., HA formation) at various time points. At the end of the culture period (14 days post-confluence), samples of the mineralized cultures were taken for further analysis using X-ray diffraction (XRD) and Fourier Transform Infra-Red Spectroscopy (FTIR). Synthetic HA doped with various Sr concentrations (based on the cell culture and previous experimental studies and yielding Sr/(Sr + Ca) ratios ranging from 0-60%), was prepared and examined for crystal growth and solubility. Crystal size was assessed using scanning electron microscopy (SEM). Ca incorporation indicated a reduced mineralization in the 20 and 100 microg/ml Sr groups vs. controls. Sr-doped synthetic HA showed a significant dose-dependent reduction in crystal growth, as assessed by SEM, and an increase in solubility, apparent from 12.7% Sr/(Sr + Ca) on. Moreover, in both mineralized cultures and synthetic HA, XRD and FTIR analysis showed a reduced crystallinity and altered crystal lattice at similar concentrations. These new data support our previous in vivo and in vitro findings and point to a potential physicochemical interference of Sr with HA formation and crystal properties in vivo.

Strontium causes osteomalacia in chronic renal failure rats.

BACKGROUND: We recently reported an association between increased bone strontium (Sr) levels and osteomalacia in dialysis patients. METHODS: To delineate whether or not Sr acts as a causal factor in the development of osteomalacia, we devised the following study: four groups of chronic renal failure (CRF) rats were given Sr, aluminum (Al), both of these compounds or none of the elements (controls). RESULTS: Administration of Sr and/or A1 resulted in increased bone levels of the respective elements. Histological examination revealed impairment of mineralization in the Sr group and to a lesser extent in the Al group as compared to the control group. There was also a significant increase in osteoid area in the Sr group, but not in the Al group. No differences in bone surface or erodic perimeter were noted between the various study groups. Histochemically, Sr could be localized in calcified bone, mainly in new bone close to the osteoid/calcification front, a critical site of bone mineralization. Histochemical findings were confirmed by electron probe X-ray microanalysis. CONCLUSIONS: These findings indicate that Sr accumulation in chronic renal failure rats resulted in the development of osteomalacic lesions, in contrast to the Al group where adynamic bone disease was induced in the present set-up. Further studies are required to define the mechanism by which way Sr causes osteomalacia in chronic renal failure rats.

Early bone formation in the human fetal otic capsule. A methodological approach.

The present study was concentrated on the use of energy-dispersive X-ray analysis and backscattered electron imaging as practical tools for advanced autopsy of human fetuses when diagnostic evaluation of ear pathology is required. These methods were used to revisit the primary calcification front of the fetal otic capsule between 18 and 36 weeks' gestational age. Energy-dispersive X-ray analysis indicates an equal Ca/P ratio in all the three layers of the otic capsule. These results are discussed in view of calcium homeostasis and inner ear function.

Early ossification within the human fetal otic capsule: morphological and microanalytical findings.

Besides the use of conventional techniques such as light and polarization microscopy, the present paper proposes the combined use of transmission electron microscopy, secondary and backscattered electron imaging, energy dispersive X-ray analysis and computed tomography for the diagnostic evaluation of ear pathology in the human fetus. These methods were used to revisit the primary calcification front of the fetal otic capsule between 16 and 23 weeks gestational age. Ultramicroscopic evaluation demonstrates similar fetal bone formation to that found in other bones of the human fetus. The formation of the endosteal and periosteal layers is a typical example of early intra-membranous ossification. The enchondral layer is made up of fibrillar bone, laid down around the calcified cartilage remnants. Microchemical analysis indicates a significantly higher Ca/P ratio in the endochondral layer with respect to the endosteum and periosteum. The consequences of a lower Ca/P ratio in the endosteal layer are discussed in view of calcium homeostasis and inner ear function.