EFFECTS OF 1,25-DIHYDROXYVITAMIN-D(3) ON BONE-RESORPTION AND NATURAL IMMUNITY IN OSTEOPETROTIC (IA) RATS

Osteopetrois is an inherited bone disease characterized by an excessiv e 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 d efects, ia rats have suppressed natural immunity, even though these an imals have excessive numbers of natural killer (NK) cells. The osteope trotic condition also appears to have an associated abnormality in vit amin D metabolism. Because 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] stim ulates bone resorption and has a role in the immunoregulation of NK ce lls, 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 par ameters 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 s ignificantly reduced in the treated animals. The elevated percentage o f NK cells normally found in ia rats was reduced to normal in the trea ted mutants, and NK cell function was elevated to normal levels of lyt ic activity. The percentage of NK cells and NK function remained uncha nged in the treated normal rats. The bone marrow cavity size was signi ficantly increased in the 1,25-(OH)2D3-treated mutants, as was the per centage of osteoclasts exhibiting normal morphology. Radiographically, the mutant bones were less dense. No net change in the bone resorptio n was noted in the treated normal rats. 1,25-(OH)2D3 appears to correc t both the bone resorption and natural immune defects in the ia osteop etrotic mutant.