Cadmium osteotoxicity in experimental animals: mechanisms and relationship to human exposures.
Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure, within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.
Bhattacharyya
Maryka H
MH
Environmental Sciences Division, Argonne National Laboratory, Lemont, IL 60439, USA. mhbhatt@anl.gov
D000818:Animals; D001847:Bone Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D018570:Risk Assessment; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D018675:Toxicity Tests; D019061:src-Family Kinases / Q000378:metabolism
D004785:Environmental Pollutants; D016760:Proto-Oncogene Proteins c-fos; D002104:Cadmium; D019061:src-Family Kinases; D002118:Calcium