Effects of 1,25-dihydroxyvitamin D3 on bone resorption and natural immunity in osteopetrotic (ia) rats.

Osteopetrois is an inherited bone disease characterized by an excessive accumulation of bone throughout the skeleton. The disease in the ia (incisors absent) rat is the result of reduced bone resorption caused by defective, although numerous osteoclasts. In addition to the bone defects, ia rats have suppressed natural immunity, even though these animals have excessive numbers of natural killer (NK) cells. The osteopetrotic condition also appears to have an associated abnormality in vitamin D metabolism. Because 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] stimulates bone resorption and has a role in the immunoregulation of NK cells, mutant and normal rats were infused with 1,25-(OH)2D3 for 14 days in an attempt to correct the defects in this mutant. Serum levels of osteocalcin, 25-OHD3, and 1,25-(OH)2D3, as well as NK function and parameters of bone resorption, were evaluated after the infusion period. Serum levels of osteocalcin and 1,25-(OH)2D3 were elevated in both ia and normal rats treated with 1,25-(OH)2D3. Serum 25-OHD3 levels were significantly reduced in the treated animals. The elevated percentage of NK cells normally found in ia rats was reduced to normal in the treated mutants, and NK cell function was elevated to normal levels of lytic activity. The percentage of NK cells and NK function remained unchanged in the treated normal rats. The bone marrow cavity size was significantly increased in the 1,25-(OH)2D3-treated mutants, as was the percentage of osteoclasts exhibiting normal morphology. Radiographically, the mutant bones were less dense.(ABSTRACT TRUNCATED AT 250 WORDS)