COMPARISON OF 22-OXACALCITRIOL AND 1,25(OH)(2)D-3 ON BONE METABOLISM IN YOUNG X-LINKED HYPOPHOSPHATEMIC MALE-MICE

Using a mouse model (Hyp) of human hypophosphatemic vitamin D-resistan t rickets [X-linked hypophosphatemia (XLH)], we compared the effects o f 22-oxa-1,25-dihydroxyvitamin D-3 (OCT) and 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] on restoring defects in mineral and skeletal metabol ism. Hyp/Y mice received OCT or 1,25(OH)(2)D-3 at doses of 0.05-0.25 m u g . kg(-1). day(-1) for 4 wk. OCT normalized serum calcium levels, w hereas 1,25(OH)(2)D-3 produced hypercalcemia in Hyp/Y. OCT and 1,25(OH )(2)D-3 also normalized serum phosphate levels and increased urinary c alcium levels. Additionally, OCT and 1,25(OH)(2)D-3 reduced elevated u rinary pyridinoline levels and suppressed urinary adenosine 3',5'-cycl ic monophosphate levels to normal. Bone ash content was low in Hyp/Y, and OCT was more effective than 1,25(OH)(2)D-3 in reversing this defec t. Histomorphometric analysis of bone turnover, mineralization rate, a nd osteoid content demonstrated comparable responses with OCT and 1,25 (OH)(2)D-3, although the highest dose of 1,25(OH)(2)D-3 resulted in in creased osteoid content and delayed mineralization. OCT appears to be more effective and definitely less toxic than 1,25(OH)(2)D-3 in revers ing skeletal lesions in Hyp/Y mice and may prove to be the drug of cho ice in the treatment of childhood XLH.