Effects of calcium salt and IGF -I infusion on calcium kinetics and bone parameters in growing rats
Abstract
Calcium is the major cation of bone mineral, the process of skeletal development and remodeling is inherently related to calcium metabolism. Kinetic modeling enables the rapid assessment of changes that occur associated with age, therapeutic intervention. Therefore, calcium metabolism was investigated using kinetic analysis in rats via several independent studies. First, calcium absorption from two different calcium salts, calcium ascorbate and calcium acetate, was compared. As measured by femur uptake, fractional calcium absorption from calcium ascorbate was substantially higher than that from calcium acetate (70% ± 5 vs. 45% ± 5) on a 25 mg test load. To further confirm this observation, a metabolic study was conducted. Four groups of male Sprague-Dawley rats (n = 10/group) received oral or intravenous doses of 25 mg Ca as calcium ascorbate or calcium acetate. Each dose contained 25 μCi 45Ci. Sequential blood, urine and fecal samples were collected over 48 hours. Data was analyzed by compartmental modeling. Results of kinetic analysis demonstrated that the higher absorption of calcium ascorbate was due to a longer residence time in the gut. Secondly, the effect of Insulin-like growth factor I (IGF-I) on calcium metabolism in growing rats was examined using the same kinetic model. IGF-I is an important mediator during pubertal skeletal growth, and has been considered as a potential treatment for osteoporosis. Measurement of bone quality and calcium metabolism were first determined in rats from age 6 weeks to 31 weeks in order to determine the timing for IGF-I intervention. Human recombinant IGF-I/IGFBP-3 complex was chronically infused into female rats at two different ages: 6 and 9 weeks of age, representing early puberty and young adulthood in humans. After 4 weeks of treatment, body weights of IGF-I treated rats were higher than control rats. Femoral calcium content was also significantly higher in IGF-I treated pubertal rats, 493 ± 42, compared to control rats, 368 ± 24 mg calcium/g ash weight. Kinetic analysis revealed the treatment resulted in higher intestinal calcium absorption and faster calcium clearance from the circulation in pubertal rats. However, the IGF-I treatment failed to alter calcium metabolism in young adult rats.
Degree
Ph.D.
Advisors
Weaver, Purdue University.
Subject Area
Nutrition
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