Effects of cadmium on bone: an in vivo model for the early response.
Cadmium (Cd) exposure induces bone resorption in vitro and in vivo that can lead to low bone mass and increased incidence of fracture. We have developed an animal model for following the early skeletal response to Cd. A low-calcium (but not calcium-deficient) diet is used to increase gastrointestinal absorption of calcium so that the endogenous fecal calcium excretion is essentially the total fecal calcium excretion. The bone response is followed by quantitation of stable fecal calcium and does not require a radioactive label. After mice were adjusted to a low-calcium diet, Cd was administered by a single gavage and fecal calcium was monitored to determine the magnitude of the calcium release from bone. Fecal calcium excretion (microg Ca/hr; mean +/- SE) remained at the background level for 8 hr (13.6 +/- 1.8, n = 18) but increased during the 8- to 24-hr and 24- to 56-hr collection periods (43.8 +/- 6.8, n = 12; 50.75 +/- 3.7, n = 6, respectively). The bone response was transient and dropped to nearly background levels during the 56- to 104-hr collection period. Blood calcium levels were normal throughout the time course. Bone resorption occurred at Cd levels of 7.9 +/- 0.7 microg/liter blood (mean +/- SE, n = 6), which is in the range of occupational exposure levels. The transient nature of the bone response contrasted to the slow but continuing rise observed in blood Cd levels. These results suggest that a threshold level of Cd is required for a bone response but that chronic levels of Cd in blood do not necessarily indicate the occurrence of continuous active bone resorption. This model can be used to probe early gene changes (prior to the bone response) that may be occurring in response to Cd exposure.
Wilson
A K
AK
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Illinois 60439-4833, USA.
Bhattacharyya
M H
MH
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced*; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects; D013058:Mass Spectrometry; D051379:Mice
D002136:Calcium, Dietary; D002104:Cadmium; D002118:Calcium