It has been suggested that in uremic bone, aluminum interferes with normal mineralization. Aluminum content and aluminum localization were studied in iliac crest biopsies of two groups of patients on regular hemodialysis; one group had histologic osteomalacia, and little or no bone resorption (group 1); the other, osteitis fibrosa and no mineralization defect (group 2). Group 1 patients had significantly higher plasma aluminum concentrations than those of group 2. No difference was found in bone aluminum content, which was above normal in both groups. In the bone samples of the osteomalacic subjects, aluminum was mainly localized at the limit between osteoid and calcified tissue, the site where the bone mineral is normally first deposited. Osteomalacia could not be related to hypocalcemia or to phosphate depletion. Active vitamin D derivatives (25-hydroxycholecalciferol and 1alpha-hydroxycholecalciferol) failed to prevent or to improve the bone disease. In the bone samples of group 2 subjects, aluminum could not be localized by the methods used, except in the two cases with greatly elevated bone aluminum, where it was mainly localized on cement lines. In group 2 subjects, immunoreactive parathyroid hormone plasma concentration, osteoclast surface, and marrow fibrosis were significantly higher than they were in group 1 subjects. It is concluded that in bone from uremic patients on regular dialysis, aluminum can induce a particular form of osteomalacia, resistant to the vitamin D active derivatives. The bone disease is only observed in the absence of severe secondary hyperparathyroidism. This suggests that parathyroid hormone may be involved in the development of the aluminum-induced mineralization defect.

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The subcellular distribution of halogenous molecules has been studied by SIMS microscopy in cultured cells of a human breast carcinoma (MCF-7 cell line). Two instruments of microanalysis were used. A low lateral resolution ion microscope (SMI 300 CAMECA) and a prototype scanning ion microscope equipped with a cesium gun that gives high lateral resolution images. This apparatus has been developed by G Slodzian, in Onera Laboratories (Office National d'Etudes et de Recherches Aérospatiales). Molecules studied by low lateral resolution ion microscope were halogenous steroids: fluorometholone, triamcinolone, bromocriptine and bromoandrosterone. Analytical images show that the first two compounds are mainly localized in the nuclear structure of MCF-7 cells whereas the last two molecules are localized in cytoplasm of these cells. Images were obtained with a resolution of 1 micron. With the scanning ion microscope, it is now possible to obtain images at the ultrastructural level. Four analytical images can be simultaneously obtained by a single scan of the imaged area, corresponding to a depth of erosion of the section of ten nm. The intranuclear distributions of three pyrimidine analogs, 5-bromo-2'-deoxyuridine, 5-iodo-2'-deoxyuridine and 5-fluorouracil have been studied in phase S and M of MCF-7 cells and these images have been compared to the distribution of sulfur, nitrogen and phosphorus. All these images have been obtained with a lateral resolution better than 100 nm.

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