Bone-forming ability of 24R,25-dihydroxyvitamin D3 in the hypophosphatemic mouse.
To determine whether 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] exerts unique biologic effects on bone, we examined the effects of the vitamin D metabolites, 24R,25(OH)2D3 and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], on the hypophosphatemic (Hyp) mouse, a model for X-linked hypophosphatemic rickets in humans. The Hyp mice were administered 1-10,000 micrograms/kg/day of 24R,25(OH)2D3, 0.01-10 micrograms/kg/day of 1 alpha,25(OH)2D3, or vehicle alone, given daily for 28 days by intraperitoneal injection. 24R,25(OH)2D3 at doses of 1-1000 micrograms/kg/day had dose-dependent effects in increasing bone size, dry bone weight, and bone mineral content without causing hypercalcemia. 1 alpha,25(OH)2D3 at doses of 1 or 10 micrograms/kg/day, which we considered to have activity similar to that of 1000 micrograms/kg/day of 24R,25(OH)2D3 with respect to cell differentiation activity, caused severe bone resorption and hypercalcemia. At 0.1 microgram/kg/day, 1 alpha,25(OH)2D3 increased bone size, similarly to a dose of 1000 micrograms/kg/day of 24R,25(OH)2D3, without significantly affecting dry bone weight or bone mineral content, as did 1000 micrograms/kg/day of 24R,25(OH)2D3. These findings suggest that 24R,25(OH)2D3 exerts unique activity in the Hyp mouse rather than merely mimicking the activity of 1 alpha,25(OH)2D3.
Yamate
T
T
Department of Pediatrics, Okayama University Medical School, Japan.
Tanaka
H
H
Nagai
Y
Y
Yamato
H
H
Taniguchi
N
N
Nakamura
T
T
Seino
Y
Y
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002117:Calcitriol / Q000008:administration & dosage* / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006934:Hypercalcemia / Q000139:chemically induced; D017674:Hypophosphatemia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011859:Radiography
D002762:Cholecalciferol; D002117:Calcitriol