Ultrastructural development of hyperosteoidosis in 1,25(OH)2D3-treated rats fed high levels of dietary calcium.
To evaluate the sequential ultrastructural pathogenesis of the increase in osseous tissue and hyperosteoidosis previously demonstrated in rats administered supraphysiologic doses of 1,25(OH)2D3 and fed high levels of dietary calcium, young adult female rats were placed on a 2.5% calcium and 0.3% phosphorus diet, administered ethanol or 135 ng (5 units) 1,25(OH)2D3 IP daily, and killed after 2, 4, 6, 8, and 10 days. Metaphyseal trabeculae from 1,25(OH)2D3 and placebo-treated rats were examined. Osteoblast hypertrophy characterized by increased cytoplasmic area, abundant rough endoplasmic reticulum, and prominent Golgi apparatus was evident in 1,25(OH)2D3-treated rats at Day 4. These osteoblasts were interpreted to be active in matrix synthesis. Widened osteoid seams were present at Day 6. Osteoblast hypertrophy and widened osteoid seams persisted through Day 10 in 1,25(OH)2D3-treated rats. The unmineralized bone matrix in 1,25(OH)2D3-treated rats contained more numerous cytoplasmic processes from adjacent osteoblasts than did control animals and loosely arranged collagen fibrils, which failed to aggregate in regions adjacent to the osteoid-mineralized bone interface as in placebo-treated rats. Osteoid seams in 1,25(OH)2D3-treated rats contained irregular electron-dense foci, which were often concentrated around embedded cytoplasmic processes. Osteocytic hypertrophy characterized by increased cytoplasmic area, developed rough endoplasmic reticulum, and increased numbers of mitochondria was evident at Day 2 and was sustained through Day 10 in 1,25(OH)2D3-treated rats. Variable-sized aggregates of electron-dense deposits similar to those concentrated around osteoblast cytoplasmic processes were observed in the pericellular space and on and immediately adjacent to the plasma membranes of osteocytes and embedding osteoblasts in 1,25(OH)2D3-treated rats as early as Day 4.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000648:ultrastructure*; D002117:Calcitriol / Q000633:toxicity*; D002136:Calcium, Dietary / Q000008:administration & dosage*; D005260:Female; D006984:Hypertrophy; D010006:Osteoblasts / Q000648:ultrastructure; D010010:Osteoclasts / Q000648:ultrastructure; D010011:Osteocytes / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D002136:Calcium, Dietary; D002117:Calcitriol