Comparison of 22-oxacalcitriol and 1,25(OH)2D3 on bone metabolism in young X-linked hypophosphatemic male mice

Abstract

Using a mouse model (Hyp) of human hypophosphatemic vitamin D-resistant rickets [X-linked hypophosphatemia (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 micron.kg-1.day-1 for 4 wk. OCT normalized serum calcium levels, whereas 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(OH)2D3 reduced elevated urinary pyridinoline levels and suppressed urinary adenosine 3',5'-cyclic monophosphate 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 mineralization. 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.