Gastrectomized rats respond with exaggerated hypercalcemia to oral and intravenous calcium loads because of impaired ability of bone to take up Ca2+.
BACKGROUND
Gastrectomy (Gx) causes osteopenia. The hypothesis tested in the present study is that Gx affects Ca homeostasis and that an impaired ability to handle Ca contributes to the Gx-evoked osteopenia.


METHODS
SHAM-operated and Gx rats were compared with respect to changes in blood Ca2+ after oral or intravenous loads of CaCl2 1-2 weeks or 2-4 months after the operations.


RESULTS
Different doses of oral CaCl2 raised blood Ca2+ more in Gx than in SHAM rats, more so after 2-4 months than after 1-2 weeks. The rise was greater in fasted (48 h) rats than in fed rats regardless of whether they were SHAM or Gx. While SHAM rats tolerated high doses of CaCl2 well, Gx rats died when exposed to quite modest doses, particularly 2-4 months after Gx. Intravenous infusion of CaCl2 (2,500 micromol/kg/h) induced a greater and steeper rise in blood Ca2+ in Gx rats than in SHAM rats. Kinetic analysis of the blood Ca2+ data showed Gx rats to display: 1) a decreased Ca2+ elimination clearance from the central distribution compartment (blood), 2) a reduced size of the peripheral distribution compartment (the so-called bone fluid compartment). and 3) a spectacular decrease in the intercompartmental clearance (transfer of Ca2+ from blood to bone). These effects were notably apparent after 2-4 months. At sacrifice, the Gx-evoked osteopenia was confirmed by planimetric analysis of the calvariae. revealing 40% reduction of bone tissue after 2-4 months.


CONCLUSIONS
Based on the present data we argue that Gx rats respond with exaggerated hypercalcemia to oral and intravenous CaCl2 loads because of a greatly impaired transfer of Ca+ from blood to bone. We suggest that with time this impairment results in osteopenia.
Surve
V V
VV
Dept. of Pharmacology, Institute of Physiological Sciences, Lund University, Sweden.
Höglund
P
P
Håkanson
R
R
D000284:Administration, Oral; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D005743:Gastrectomy / Q000009:adverse effects*; D006706:Homeostasis / Q000502:physiology; D006934:Hypercalcemia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D002118:Calcium