RECENT ADVANCES IN STUDIES OF ITAI-ITAI-D ISEASE

The recent studies of Itai-itai disease (IID) which have been mainly c onducted since 1980 is reviewed. Fifty-one patients were officially de signated as having IID from 1980 to 1996. The latest patient registere d in 1994 complained of having a bone pain at the age of 72 in 1991. T his fact indicates the occurrence of new cases of IID even today. In 7 5 autopsy cases of IID (1979-1991), Looser zones, which are characteri stic of osteomalacia, were observed in 45 (60%). A large number of Loo ser zones were found in the ribs (356), femur (44), ulna (12), pubic r amus (9) and other bones. The most conspicuous feature of bone histopa thology 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 atr ophic 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. An emia and hypocalcemia, found in the endstage of IID, were closely asso ciated with an impaired renal function. Extensive measurements of heav y metals in the organs derived from the autopsy cases of IID have show n significantly lower values of Cd, Zn, and Cu in the kidneys, whereas significantly higher values of Cd and Zn were found in the liver, pan creas, thyroid and other organs compared to the control group. It can be inferred that the kidneys of those with IID once had high concentra tions of Cd which had been excreted into the urine, associated with th e ablation of tubular epithelium. On the based of these findings, the pathogenesis of IID is discussed.