Cadmium effects on bone metabolism: accelerated resorption in ovariectomized, aged beagles.
The purpose of this study was to evaluate, in an animal whose skeleton is comparable to humans, the combined effects of estrogen depletion and Cd exposure on bone resorption by monitoring skeletal release of 45Ca and to determine whether Cd-induced bone resorption occurred independent of osteotropic hormone changes and renal dysfunction. Cd exposure following ovariectomy or sham surgery was for 7 months: 1 month by oral ingestion of capsules (1, 5, 15, 50 ppm) and 6 months via drinking water (15 ppm). Serum and fecal 45Ca were increased at 1 week following ovariectomy (OV) (54 +/- 9% and 122 +/- 40%, respectively), but this response was attenuated by 2 weeks. Five of seven exposed dogs had increased serum and fecal 45Ca during the 50-ppm Cd capsule period (15-40% and 15-190%, respectively). Serum 45Ca levels in OV/+Cd dogs showed a significant and consistent increase within 1 week of initiating each of three separate Cd.H2O exposure cycles. Blood Cd levels increased over time from 2 to 15 micrograms/l, coinciding with the elevated serum 45Ca concentrations. No correlation was observed between serum 45Ca increases and parathyroid hormone, 1,25-(OH)2-vitamin D, or calcitonin. No effects of ovariectomy and/or Cd were observed in total serum Ca, calciotropic hormone concentrations, serum or urinary phosphorus and creatinine, creatinine clearance, or urinary specific gravity. Urinary Cd concentrations ranged from 7 to 50 micrograms/l in exposed dogs but were not detectable in nonexposed dogs. Urinary protein concentrations showed no differences between groups. Cd increased bone resorption (skeletal 45Ca release) in ovariectomized and sham-operated dogs without renal dysfunction or calciotropic hormone interaction. Based on our results, Cd is an exogenous factor which exacerbates bone mineral loss in postmenopausal osteoporosis.
Sacco-Gibson
N
N
Biological and Medical Research Division, Argonne National Laboratory, Illinois 60439-4833.
Chaudhry
S
S
Brock
A
A
Sickles
A B
AB
Patel
B
B
Hegstad
R
R
Johnston
S
S
Peterson
D
D
Bhattacharyya
M
M
D000375:Aging / Q000378:metabolism; D000818:Animals; D001822:Body Burden; D001835:Body Weight / Q000187:drug effects; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D004285:Dogs; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D010052:Ovariectomy; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism
D002104:Cadmium; D003300:Copper; D003404:Creatinine; D015032:Zinc; D002118:Calcium