Morehead State University
Effects of Various Calcium Channel Antagonist on Estrogen-Regulated Bone Resorption
Institution
Morehead State University
Faculty Advisor/ Mentor
Darrin Lee DeMoss
Abstract
Bone metabolism is invariably correlated with calcium transport. Therefore, calcium channels are a potential point of regulation for skeletal remodeling. Calcium channel antagonists are utilized therapeutically and experimentally to decrease the influx of calcium into cells by blocking voltage-regulated L-type calcium channels. 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 experimentation utilized female Brown Norway Rats six months of age to compare the effects of estrogen and the antagonists on calcium flux in both the amorphous and calcified compartments. The model utilized to study bone resorption involved a pharmacokinetic study of 3H-tetracycline, a compound deposited in the active mineralization front. Experimental evidence suggests that calcium antagonists decrease osteoblastic activity, thus decreasing the activity of the bone forming cells at a time when bone formation is already exceeded by bone resorption, thus exacerbating the situation. It is also known that there is a ten-year lag in the age-related rise in cardiovascular mortality in women compared to men. Therefore, the established principle of decreasing bone formation resulting in increased bone resorption following the attainment of peak bone mass illustrates the need for a more comprehensive understanding of the action of these drugs and an improved understanding of the protective action estrogen appears to have on skeletal mass.
Effects of Various Calcium Channel Antagonist on Estrogen-Regulated Bone Resorption
Bone metabolism is invariably correlated with calcium transport. Therefore, calcium channels are a potential point of regulation for skeletal remodeling. Calcium channel antagonists are utilized therapeutically and experimentally to decrease the influx of calcium into cells by blocking voltage-regulated L-type calcium channels. 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 experimentation utilized female Brown Norway Rats six months of age to compare the effects of estrogen and the antagonists on calcium flux in both the amorphous and calcified compartments. The model utilized to study bone resorption involved a pharmacokinetic study of 3H-tetracycline, a compound deposited in the active mineralization front. Experimental evidence suggests that calcium antagonists decrease osteoblastic activity, thus decreasing the activity of the bone forming cells at a time when bone formation is already exceeded by bone resorption, thus exacerbating the situation. It is also known that there is a ten-year lag in the age-related rise in cardiovascular mortality in women compared to men. Therefore, the established principle of decreasing bone formation resulting in increased bone resorption following the attainment of peak bone mass illustrates the need for a more comprehensive understanding of the action of these drugs and an improved understanding of the protective action estrogen appears to have on skeletal mass.