Inhibition by aminohydroxypropylidene bisphosphonate (AHPrBP) of 1,25(OH)2 vitamin D3-induced stimulated bone turnover in the mouse.
The purpose of this study was to evaluate whether the 1,25(OH)2D3-induced increased bone mineralization in the mouse occurs in response to stimulation of bone resorption. In order to inhibit bone resorption, 35-day-old mice were given 16 mumol/kg/day of (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (AHPrBP) for 10 days, the first injection occurring 3 days prior to the continuous infusion of 0.06, 0.13, or 0.20 micrograms/kg/day of 1,25(OH)2D3 for 7 days. Two groups of mice were treated with AHPrBP or 1,25(OH)2D3 alone. The skeletal changes were assessed by histomorphometric study of caudal vertebrae after double 3H-proline and double tetracycline labelings for evaluation of the matrix apposition rate (MaAR) and mineral apposition rate (MiAR), respectively. Treatment with AHPrBP alone or combined to 1,25(OH)2D3 decreased the number of acid phosphatase-stained osteoclasts and reduced the endosteal MaAR and MiAR and the amount of osteoid. When given alone, 1,25(OH)2D3 increased serum calcium above normal, enhanced the number of histochemically active osteoclasts, and stimulated the endosteal MiAR. Pretreatment with AHPrBP blocked both the increase in serum calcium and the stimulation of the MiAR induced by 1,25(OH)2D3 infusion though serum 1,25(OH)2D3 levels rose according to the dose given. The results show that 1) the serum calcium and the bone resorbing responses to 1,25(OH)2D3 infusion are prevented by pretreatment with AHPrBP, and 2) the stimulatory effect of 1,25(OH)2D3 on the mineralization rate is blocked when bone resorption is inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001857:Bone Matrix / Q000378:metabolism; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002117:Calcitriol / Q000037:antagonists & inhibitors* / Q000097:blood; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology*; D006128:Growth / Q000187:drug effects; D008297:Male; D051379:Mice; D000077268:Pamidronate; D010710:Phosphates / Q000097:blood
D004164:Diphosphonates; D010710:Phosphates; D000469:Alkaline Phosphatase; D002117:Calcitriol; D000077268:Pamidronate; D002118:Calcium