Itai-itai disease is thought to be the result of chronic
cadmium (Cd) intoxication. We examined 23 autopsy cases of
itai-itai disease and 18 cases of
sudden death as controls. Urine and blood samples from 10 patients were collected before they died and revealed the presence of severe
anemia and renal tubular
injuries. Undecalcified sections of iliac bone were stained with
Aluminon reagent, and
ammonium salt of
aurintricarboxylic acid, and
Prussian blue reagent in all cases of
itai-itai disease. These two
reagents reacted at the same mineralization fronts. X-ray microanalysis revealed the presence of
iron at mineralization fronts in
itai-itai disease. Five patients showed evidence of
hemosiderosis in the liver, spleen, and pancreas, probably as a result of post transfusion
iron overload.
Renal calculi and calcified aortic walls were also stained with
Prussian blue reagent in several patients. Neither
ferritin nor
transferrin were visualized at mineralization fronts in
itai-itai disease by immunohistochemical staining. These results suggest that
iron is bound to
calcium or to
calcium phosphate by a physicochemical reaction. A marked
osteomalacia was observed in 10 cases of
itai-itai disease by histomorphometry. Regression analyses of data from cases of
itai-itai disease suggested that an
Aluminon-positive
metal inhibited mineralization and that renal tubules were injured. Since bone Cd levels were increased in
itai-itai disease, it is likely that renal tubules were injured by exposure to Cd. Therefore, stainable bone
iron is another possible aggravating factor for osteopathy in
itai-itai disease, and a synergistic effect between
iron and Cd on mineralization is proposed.