EFFECTS OF CALCIUM DEPLETION AND REPLETION ON SERUM INSULIN-LIKE-GROWTH-FACTOR-I AND BINDING-PROTEIN LEVELS IN WEANLING RATS

Previous studies in a weanling rat model indicated that dietary calciu m depletion not only stimulated osteoclastic resorption but also inhib ited bone formation, The present study sought to test whether the depl etion-associated inhibition of bone formation is related to a reductio n in serum insulin-like growth factor-I (IGF-I) and/or an increase in its binding proteins (IGFBPs), Twenty male weanling rats were divided into two weight-matched groups, The study group was subjected to a sem isynthetic diet deficient in calcium (0.02% calcium) for 28 days, whil e the control group was pair-weighed on the same diet but containing 0 .62 % calcium, After the depletion phase, all rats were fed the same c alcium-containing diet for an additional 14 days. Serum samples were o btained from each animal on a weekly basis and assayed for IGF-I and I GFBPs, During depletion, there was no statistically significant differ ence in serum IGF-I level between the study group and the control grou p, In contrast, the study group showed a statistically significant inc rease in several serum IGFBPs with apparent molecular size of 30 -38 k D (IGFBP-3), 26-28 kD (IGFBP-1, -2, -5, and/or -6), and 24-25 kD (IGFB P-4), respectively, compared to the control group, There was no differ ence in nutritional intakes between the two groups of rats during depl etion, During repletion, there was also no significant difference in s erum IGF-I level between the control and study group. However, during the first 7 days of repletion, serum IGFBP-3 and the 26-28 kD IGFBP of the study group was significantly less than those of the control grou p, which then returned to the control level after 2 weeks of repletion , In summary: (1) calcium depletion in weanling rats increased several serum IGFBPs without an effect on IGF-I; and (2) calcium repletion in duced an acute reduction in serum IGFBP-3, In conclusion, these findin gs represent the first evidence that the depletion-related inhibition of bone formation in the rat may be associated with an increase in sev eral serum IGFBPs, which may act to inhibit the osteogenic actions of IGFs. (C) 1998 by Elsevier Science Inc. All rights reserved.