Life-span study on late effects of 224Ra in children and adults

Between 1945 and 1955, several thousand patients were injected with Peteosthor, a preparation containing Radium-224 (Ra), as treatment for bone tuberculosis or ankylosing spondylitis. Ra, like Pu, is a bone seeking nuclide. During the course of early experimental work it became clear in 1948 that the short lived alpha-emitter Ra concentrates predominantly in the growing zones of the bones. Consequently, I released strong official warnings, at the 1950 German Congress of Orthopedics, against Peteosthor, and especially against its administration to juvenile patients-still in their period of growth. Epidemiological investigations were then initiated on a study population that comprises 899 persons (including 217 children or juveniles) who received injections of Ra. The study has now been conducted for a follow-up period of over 60 y. The most striking detrimental health effect following Ra injections are a large number of malignant bone tumors that occurred predominantly in childhood. This finding was the reason for my invitation to the first conference on "Delayed Effects of Bone seeking Radionuclides" in Sun Valley, ID, in September 1967, a meeting that was organized by Charles Mays. I reported on 50 Ra-induced bone tumors in children and adults, growth disturbances, osteochondroma, and cataracts, concluding that the younger the age at Ra injection, the more severe the late effects. Up to now 57 malignant bone tumors have been observed while less than one case would have been expected. The peak occurred 8 y after the first Ra injection and the last bone sarcoma arose 46 y after injection. A total of 270 non-skeletal malignant diseases were observed against a statistical expectation of 192 cases, the excess risk of mammary cancers in those treated in childhood being particularly striking. In the past two years increases of non-cancer diseases have become apparent in the exposed group compared to a control group of 166 living members with no exposure to Ra. Although 124 study group members are still alive, only the 81 members with ages at or below the maximum age in the control group were included in this comparison in order to attain approximate age matching. The breakdown of these diseases is kidney insufficiency, 12 (15%) study group members vs. 3 (2%) controls, where 5 (6%) study group members required dialysis vs. 2 (1%) controls; thyroid disease (struma nodosa), 28 (35%) study group members vs. 29 (17%) controls; heart attack, 8 (10%) study group members vs. 4 (2%) controls; coronary heart disease, 9 (11%) study group members vs. 8 (5%) controls.