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 attentuated 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 μg/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 μg/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.
|Original language||English (US)|
|Number of pages||10|
|Journal||Toxicology and Applied Pharmacology|
|State||Published - Apr 1992|
Bibliographical noteFunding Information:
’ This work is supported in part by the National Institutes of Health Grant ES048 16 and by the U.S. Department of Energy, Office of Health and Environmental Research, under Contract W-31-109-ENG-38 and in part by Minnesota Agricultural Station Project MIN-62-055. Preliminary data presented at the 74th Annual FASEB meeting in Washington, D.C., April 1990. 2 The submitted manuscript has been authored by a contractor of the U.S. Government under contract W-3 I-109-ENG-38. Accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes.