The effect of 1,25 (OH)2D3 on bone mineralization: ultrastructural studies in patients with renal osteodystrophy

The acute effects (15-50 days) of 1,25(OH)2D3 (0.5-2 microgram/day) on the histological, fluorescence-microscopical and ultrastructural appearance of mineralizing osteoid in iliac crest spongiosa were studied in 6 uremic patients on maintenance hemodialysis. While there was a marked decrease on endosteal fibrosis and osteoclast counts, volumetric and surface densities of osteoid continued to stay elevated during the observation period. The number of osteoid seams with tetracycline double label increased in 4/6 patients but no such seams appeared in 2 patients who had shown only nonlabeled seams with diffuse staining of osteoid prior to therapy. In studies with transmission electron microscopy, the interface between non-mineralized osteoid and mineralized bone was irregularly outlined and broad. In contrast to normals, coarse mineral deposits were widely scattered in the nonmineralized osteoid. The mineral deposits had two different appearances, presumable depending on the plane of section relative to the direction of collagen fiber bundles: patches of microcristalline deposits encircling perpendicularly cut non-mineralized collagen bundles and needle- or plate-shaped crystals following the striation pattern of collagen fibers. The findings point to close interaction between the pattern of mineral deposition and collagen texture. The latter was highly irregular (woven) in all uremic patients. Mineral deposits were in part normal and in part highly abnormal in texture, the latter particularly in sites with irregular collagen texture. Upon therapy, no consistent change of the ultrastructure of the mineralizing osteoid/bone interface was observed by transmission or scanning and electron microscopy.