Recent Advances in Studies of Itai-itai Disease.

Abstract

The recent studies of Itai-itai disease (IID) which have been mainly conducted since 1980 is reviewed. Fifty-one patients were officially designated as having IID from 1980 to 1996. The latest patient registered in 1994 complained of having a bone pain at the age of 72 in 1991. This fact indicates the occurrence of new cases of IID even today. In 75 autopsy cases of IID (1979-1991), Looser zones, which are characteristic of osteomalacia, were observed in 45 (60%). A large number of Looser zones were found in the ribs (356), femur (44), ulna (12), pubic ramus (9) and other bones. The most conspicuous feature of bone histopathology was a marked osteoid accumulation accompanied by the reduction of a bone mass. Loss of bone evaluated by densitometry was related to the severity of renal tubular dysfunction. The renal lesion of IID is characterized by tubulointerstitial nephropathy, and the grade of atrophic changes in tubules in the renal cortex correlates quantitatively with a decrease in kidney weight. The renal function assessed by long-term observation of serum creatinine showed a sustained reduction. Anemia and hypocalcemia, found in the end-stage of IID, were closely associated with an impaired renal function. Extensive measurements of heavy metals in the organs derived from the autopsy cases of IID have shown significantly lower values of Cd, Zn, and Cu in the kindneys, whereas significantly higher values of Cd and Zn were found in the liver, pancreas, thyroid and other organs compared to the control group. It can be inferred that the kidneys of those with IID once had high concentrations of Cd which had been excreted into the urine, associated with the ablation of tubular epithelium. On the based of these findings, the pathogenesis of IID is discussed.