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Rescue of the Pseudo‐Vitamin D Deficiency Rickets Phenotype of CYP27B1‐Deficient Mice by Treatment With 1,25‐Dihydroxyvitamin D 3 : Biochemical, Histomorphometric, and Biomechanical Analyses
Author(s) -
Dardenne Olivier,
Prud'Homme José,
Hacking S Adam,
Glorieux Francis H,
StArnaud René
Publication year - 2003
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 - 10.1359/jbmr.2003.18.4.637
Subject(s) - rickets , osteomalacia , vitamin d and neurology , medicine , endocrinology , secondary hyperparathyroidism , vitamin d deficiency , calcitriol , hyperparathyroidism , phenotype , biology , calcium , parathyroid hormone , gene , biochemistry
The treatment of choice for pseudo‐vitamin D deficiency rickets (PDDR), caused by mutations in the 25‐hydroxyvitamin D‐1α‐hydroxylase ( CYP27B1 ; 1α‐OHase ) gene, is replacement therapy with 1,25(OH) 2 D 3 . We have previously engineered an animal model of PDDR by targeted inactivation of the 1α‐OHase gene in mice. Replacement therapy was performed in this model. The 1α‐OHase −/− mice and heterozygote controls were treated with 500 pg of 1,25(OH) 2 D 3 /g body weight/day for 2 weeks, followed by 100 pg of 1,25(OH) 2 D 3 /g body weight/day for an additional 3 weeks before death at 8 weeks of age. Blood biochemistry analysis revealed that the rescue treatment corrected the hypocalcemia and secondary hyperparathyroidism. The daily injections of 1,25(OH) 2 D 3 induced strong expression of CYP24 , the 25‐hydroxyvitamin D 24‐hydroxylase gene. Bone histology and histomorphometry confirmed that the rickets and osteomalacia were cured. The rescue regimen also restored the biomechanical properties of the bone tissue within normal parameters. These results show that chronic treatment with the active 1,25(OH) 2 D 3 metabolite is effective to rescue the PDDR phenotype of 1α‐OHase mutant mice.