Use of the (3)H-Tetracycline rat model in the study of skeletal compartmentalization and metabolism of calcium in the maturing male and female rat and the role of the skeleton in calcium homeostasis in the adolescent male rat
Date of Award
Joan C. Edwards School of Medicine
Type of Degree
Leonard J. Deutsch
The (3)H-tetracycline bone labeling procedure was employed to monitor bone resorption from urinary loss curves in male and female rats of various ages. In addition, whole body dry skeletal mass and the loss of (3)H-tetracycline from individual bones was determined. It was found that the dry skeletal mass/body mass ratio of 24-week-old females was 30-40% greater than that for males. The urinary loss of (3)H-tetracycline was described by a double exponential equation indicating the presence of two distinct and independent exchangeable bone compartments. Both compartments decrease in size with age, but their label loss activities were different. The label loss activity within the rapidly depleted compartment, which we suggest reflects calcium loss from the bone fluid compartment, was "inert” in the sense that it did not change with age or between sexes. Label loss activity in the slowly depleted compartment, which we suggest represents the active resorption of calcified bone, was increased with aging. Despite a smaller skeletal mass, resorptive activity in this compartment was higher in female rats than in male rats by 24 weeks of age due to a larger compartment size and the maintenance of a high rate of resorptive activity. In addition, the effect of dietary calcium on skeletal bone metabolism was investigated in adolescent Sprague Dawley male rats labeled with (3)H-tetracycline. As dietary calcium decreased in concentration from 5.0% to 0.02%, no effect was observed on body mass. However, an increase in pool size and the rate of turnover, without any change in pool depletion time, was detected for both the bone fluid and calcified bone compartments. The decrease in dietary calcium resulted in the elevation of calcium loss from the bone fluid compartment at a dietary calcium threshold of 2.5%, which was higher than the threshold for increased calcium loss from the calcified compartment (dietary calcium level of 1.5%). This observation suggests a physiological role for each bone compartment in the maintenance of plasma calcium homeostasis. These mechanisms appear to function in a precise manner in order to provide protection for both the plasma calcium concentration and the maintenance of skeletal health in the face of a homeostatic challenge. However, under conditions of severe calcium stress both compartments are affected detrimentally. The bone fluid compartment, which functions to buffer the moment-to-moment fluctuations of plasma calcium, appears to have been depleted of its calcium stores as evidenced by a decrease in bone calcium content. However, the loss of bone from the calcified compartment responds initially with an increase in bone resorption from only bones of the appendicular skeleton, thus protecting the bones of the axial skeleton which possess a greater percentage of trabecular bone. Under continued severe calcium stress the calcified compartment displays a decrease in overall skeletal health as evidenced by the significant decrease in individual dry bone mass.
Calcium – Physiological effect.
DeMoss, Darrin Lee, "Use of the (3)H-Tetracycline rat model in the study of skeletal compartmentalization and metabolism of calcium in the maturing male and female rat and the role of the skeleton in calcium homeostasis in the adolescent male rat" (1996). Theses, Dissertations and Capstones. 1471.