Morehead State University
The Effect of Calcium Channel Antagonists on Bone Metabolism in Male Brown Norway Rats
Institution
Morehead State University
Faculty Advisor/ Mentor
Darrin DeMoss
Abstract
Bone metabolism is invariably correlated with calcium transport indicating that 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. Previous experimental evidence has suggested that calcium channel 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, exacerbating the situation. Therefore, 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. Experimentation utilized male and female Brown Norway Rats six months of age to compare the effects of 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 various calcium channel antagonists on bone loss, bone resorption parameters were compared between normal males and females, and animals receiving calcium channel antagonists (diltiazem, nifedipine, verapamil). 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. Data obtained suggest that calcium channel antagonists potentially elicit their actions through alternative mechanisms in each of these highly regulated calcium pools.
The Effect of Calcium Channel Antagonists on Bone Metabolism in Male Brown Norway Rats
Bone metabolism is invariably correlated with calcium transport indicating that 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. Previous experimental evidence has suggested that calcium channel 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, exacerbating the situation. Therefore, 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. Experimentation utilized male and female Brown Norway Rats six months of age to compare the effects of 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 various calcium channel antagonists on bone loss, bone resorption parameters were compared between normal males and females, and animals receiving calcium channel antagonists (diltiazem, nifedipine, verapamil). 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. Data obtained suggest that calcium channel antagonists potentially elicit their actions through alternative mechanisms in each of these highly regulated calcium pools.