Continuous infusion of 1,25-dihydroxyvitamin D3 stimulates bone turnover in the normal young mouse.
The effects of continuous administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on mineral and bone metabolism have been examined in the normal mouse. Four doses (0.05-0.25 micrograms/kg/day) of 1,25(OH)2D3 were infused continuously for 4 weeks in 21-day-old intact animals. Mineral and skeletal changes were evaluated by analytical methods and by histomorphometric analysis of endosteal bone formation and resorption parameters. All doses of 1,25(OH)2D3 increased the fractional osteoclastic surface and the osteoclast number in conjunction with increased hydroxyproline excretion. 1,25(OH)2D3 induced a dose-dependent elevation of the calcification rate, reduction of the mean osteoid seam thickness, and shortening of the mineralization lag time. In addition, there was a dose-related increase in the extent of tetracycline double-labeled osteoid surface and a concurrent rise in the fractional osteoblastic surface associated with elevated serum alkaline phosphatase levels. Increased bone formation appeared to have been balanced by increased bone resorption since the trabecular bone volume remained unchanged. Except at the highest dose given, serum calcium and phosphate concentrations remained normal in spite of increased bone mobilization and presumably enhanced intestinal absorption of minerals. Urinary cAMP and TmP/GFR remained normal, suggesting that parathormone secretion was not altered. The results show that continuous 1,25(OH)2D3 infusion in the young mouse produces a dose-dependent stimulation of bone mineralization rate in response to increased osteoclastic bone resorption. The data indicate that 1,25(OH)2D3 can regulate bone turnover as well as mineral homeostasis in the young mouse.
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism
D010710:Phosphates; D000469:Alkaline Phosphatase; D002117:Calcitriol; D006909:Hydroxyproline; D002118:Calcium