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Effects of 1,25‐dihydroxyvitamin D 3 on bone resorption and natural immunity in osteopetrotic ( ia ) rats
Author(s) -
Schneider Gary B.,
Relfson Melanie,
Langman Craig B.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090419
Subject(s) - endocrinology , medicine , bone resorption , resorption , osteocalcin , bone remodeling , osteopetrosis , bone marrow , chemistry , vitamin d and neurology , natural killer cell , biology , alkaline phosphatase , cytotoxicity , biochemistry , in vitro , enzyme
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 D 3 [1,25‐(OH) 2 D 3 ] stimulates bone resorption and has a role in the immunoregulation of NK cells, mutant and normal rats were infused with 1,25‐(OH) 2 D 3 for 14 days in an attempt to correct the defects in this mutant. Serum levels of osteocalcin, 25‐OHD 3 , and 1,25‐(OH) 2 D 3 , as well as NK function and parameters of bone resorption, were evaluated after the infusion period. Serum levels of osteocalcin and 1,25‐(OH) 2 D 3 were elevated in both ia and normal rats treated with 1,25‐(OH) 2 D 3 . Serum 25‐OHD 3 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) 2 D 3 ‐treated mutants, as was the percentage of osteoclasts exhibiting normal morphology. Radiographically, the mutant bones were less dense. No net change in the bone resorption was noted in the treated normal rats. 1,25‐(OH) 2 D 3 appears to correct both the bone resorption and natural immune defects in the ia osteopetrotic mutant.