Effects of alendronate on plasma calcium levels, urinary calcium excretion, and bone resorption markers in normal rats: comparison with elcatonin, synthetic eel calcitonin.
In normal rats given alendronate (0.01-6.25 mg/kg) or elcatonin (synthetic eel calcitonin; 0.32-8.0 U/kg), changes in urinary calcium (Ca), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) excretion during the hypocalcemic response were assessed. Although the lower doses (0.01-0.25 mg/kg) of alendronate did not influence plasma Ca, the high doses (1.25-6.25 mg/kg) significantly decreased plasma Ca by the third day after single iv administration. In these groups, urinary Ca excretion did not show any significant change, but urinary Pyr and D-Pyr excretion decreased significantly at high doses. The hypocalcemic effect lasted for only 1 or 2 days (2-3 days after injection) even at high doses of alendronate. In the group receiving elcatonin (8.0 U/kg, twice daily), a significant decrease in plasma Ca was evident as early as 1 day after the start of administration. This was accompanied by a marked increase in urinary Ca excretion in the early stage without a significant decrease in urinary Pyr or D-Pyr excretion, and the suppression of bone resorption was more pronounced in the late phase of treatment with elcatonin. These results suggest that alendronate decreases plasma Ca chiefly by suppressing bone resorption, whereas elcatonin decreases plasma Ca by inhibiting bone resorption and accelerating Ca excretion. The present data show that both alendronate and elcatonin inhibit bone resorption and exert an antihypercalcemic effect, but the mechanism of action is different in the two drugs.
Azuma
Y
Y
Pharmacological Research Department, Teijin Institute for Biomedical Research, Tokyo, Japan.
Chokki
M
M
Ohta
T
T
Kiyoki
M
M
D019386:Alendronate; D000596:Amino Acids / Q000652:urine; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002116:Calcitonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000097:blood* / Q000652:urine*; D002940:Circadian Rhythm; D004164:Diphosphonates / Q000494:pharmacology*; D008297:Male; D010710:Phosphates / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D004164:Diphosphonates; D010710:Phosphates; C015484:pyridinoline; C036020:deoxypyridinoline; D002116:Calcitonin; D002118:Calcium; C012755:elcatonin; D019386:Alendronate