INTERACTIVE EXHIBITION OF HEAVY-METAL TOXICITY IN BONE METABOLISM - FROM THE VIEWPOINT OF DEDUCTIVE TOXICOLOGY

''Toxicology'' includes a broad range of application such as environmental, clinical and forensic toxicology. These several kinds of applied toxicology forms a mutually connected ring. This ring is supported by a column called as deductive and detective analysis by the author. ''Deductive toxicology'' is a way of thinking to solve toxicological problems more multidimensionally. In this paper, an application of this way to the study of bone lesions observed in Itai-itai diseased patients is described. In cultured embryonic chick bone, both cadmium and copper induced an atrophic change of the osseous tissue. However, zinc induced an osteomalacic change as a result of strong inhibition of calcification. These histological changes were supported by investigation using a culture system of osteoblastic MC3T3-E1 cells. Cadmium stimulated bone resorption in a neonatal parietal bone. In addition, cadmium stimulated the formation of osteoclast-like cells in bone marrow cell culture. It is thus suggested that cadmium and copper are factors of osteoporosis whereas zinc is a factor of osteomalacia when they directly act on bone tissues. A simultaneous exposure of cadmium and zinc to cultured bones resulted in an osteomalacic change with or without inhibition of bone matrix formation. Copper caused an atrophic change in the absence or the presence of zinc. A combination of cadmium and copper induced a severe damage of osteoblasts and osteogenic mesenchymal eels. These results suggested that an interactive exhibition of heavy metal toxicity can cause various bone lesions such as osteomalacia, osteoporosis and osteoporomalacia. The idea that heavy metals can directly act on bone tissues and their interaction can induce various histological changes in the tissue will help an understanding of bone lesions in Itai-itai disease.