Comparison of 22-oxacalcitriol and 1,25(oh)2d3 on bone metabolism
in young x-linked hypophosphatemic male mice.
Halstead, Linda R., Robert S. Weinstein*, Su-Li Cheng, Leonard Rifas,
and Louis V. Avioli.
Department of Internal Medicine, Division of Bone and Mineral
Diseases, Washington University School of Medicine and the Jewish
Hospital of St. Louis, St. Louis, Missouri and Department of Internal
Medicine, Division of Endocrinology/Metabolism, University of
Arkansas, Little Rock, Arkansas
APStracts 2:0192E, 1995.
Utilizing a mouse model (Hyp) of human hypophosphatemic vitamin D
-resistant rickets (XLH), we compared the effects of 22-oxa-1,25
-dihydroxyvitamin D3 (OCT) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
on restoring defects in mineral and skeletal metabolism. Hyp/Y mice
received OCT or 1,25(OH)2D3 at doses of 0.05-0.25 _g/kg/day for four
weeks. OCT normalized serum calcium levels while 1,25(OH)2D3 produced
hypercalcemia in Hyp/Y. OCT and 1,25(OH)2D3 also normalized serum
phosphate levels and increased urinary calcium levels. Additionally,
OCT and 1,25(OH2D3 reduced elevated urinary pyridinoline levels and
suppressed urinary cAMP levels to normal. Bone ash content was low in
Hyp/Y, and OCT was more effective than 1,25(OH)2D3 in reversing this
defect. Histomorphometric analysis of bone turnover, mineralization
rate, and osteoid content demonstrated comparable responses with OCT
and 1,25(OH)2D3 , although the highest dose of 1,25(OH)2D3 resulted
in increased osteoid content and delayed minerlization. OCT appears
to be more effective and definitely less toxic than 1,25(OH)2D3 in
reversing skeletal lesions in Hyp/Y mice and may prove to be the drug
of choice in the treatment of childhood XLH.
Received 4 April 1995; accepted in final form 7 August 1995.
APS Manuscript Number E161-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95