Morehead State University
Influence of Calcium Channel Antagonists on Estrogen-Regulated Bone Resorption
Institution
Morehead State University
Faculty Advisor/ Mentor
Darrin DeMoss; Micheal Fultz; David Peyton; Carol Wymer
Abstract
Bone metabolism is invariably correlated with calcium transport. Calcium channel antagonists are utilized therapeutically and experimentally to decrease the influx of calcium into cells by blocking voltage-regulated L-type calcium channels. The established principle that bone formation decreases following the attainment of peak bone mass, illustrates the need for a more comprehensive understanding of the action calcium channel antagonists have on bone turnover and an improved understanding of the protective action estrogen exerts on skeletal mass. Experimentation utilized female Brown Norway Rats six months of age to compare the effects of estrogen and the antagonists on blood pressure and bone turnover from both the amorphous and calcified compartments. In order to evaluate the positive or negative impact of estrogen and various calcium channel antagonists on bone loss, bone resorption parameters were compared between normal females, estrogen-deficient females, females receiving hormone replacement therapy, and females receiving calcium channel antagonists (Diltiazem, Nifedipine, Verapamil), or females receiving a combination of the two agents. The models utilized to study bone turnover were the pharmacokinetic loss of the tracer ³H-tetracycline, a compound deposited in the active mineralization front and freely released in urine and the measurement of various bone degradation markers (deoxypyridinoline, pyridinoline, and helical peptide) in urine collected throughout the experimental period. Ovariectomized females display an increased turnover rate while those receiving hormone replacement therapy were not significantly different from controls. Data obtained suggest that calcium channel antagonists potentially elicit their actions through alternative mechanisms in each of these highly regulated calcium pools.
Influence of Calcium Channel Antagonists on Estrogen-Regulated Bone Resorption
Bone metabolism is invariably correlated with calcium transport. Calcium channel antagonists are utilized therapeutically and experimentally to decrease the influx of calcium into cells by blocking voltage-regulated L-type calcium channels. The established principle that bone formation decreases following the attainment of peak bone mass, illustrates the need for a more comprehensive understanding of the action calcium channel antagonists have on bone turnover and an improved understanding of the protective action estrogen exerts on skeletal mass. Experimentation utilized female Brown Norway Rats six months of age to compare the effects of estrogen and the antagonists on blood pressure and bone turnover from both the amorphous and calcified compartments. In order to evaluate the positive or negative impact of estrogen and various calcium channel antagonists on bone loss, bone resorption parameters were compared between normal females, estrogen-deficient females, females receiving hormone replacement therapy, and females receiving calcium channel antagonists (Diltiazem, Nifedipine, Verapamil), or females receiving a combination of the two agents. The models utilized to study bone turnover were the pharmacokinetic loss of the tracer ³H-tetracycline, a compound deposited in the active mineralization front and freely released in urine and the measurement of various bone degradation markers (deoxypyridinoline, pyridinoline, and helical peptide) in urine collected throughout the experimental period. Ovariectomized females display an increased turnover rate while those receiving hormone replacement therapy were not significantly different from controls. Data obtained suggest that calcium channel antagonists potentially elicit their actions through alternative mechanisms in each of these highly regulated calcium pools.