224Ra-induced osteopenia in male CBA mice

Six groups of young adult, male mice were injected with six dose levels of the bone-seeking, alpha-emitting radionuclide 224Ra (half-life 3.6 days); a seventh group was injected with saline alone. The administered doses were relatively low, ranging from 2 to 64 kBq per animal. The mice were maintained under standard laboratory conditions until they either died or became moribund, when they were killed. The mean ages at death of the experimental groups were not significantly different from the normal control group. Individual bones--the mandible, parietal, nasal, and bulla--were isolated and standard linear measurements and dry weights were obtained. In all measurements considered, the highest two administered amounts (32 and 64 kBq) caused a significant reduction relative to controls. Low power microscopy of the mandible revealed osteonecrosis in the high dose groups. This is similar to the condition of "radium jaw" which has been described as a late effect of either accidental ingestion or therapeutic administration of 226Ra (half-life 1,620 years) in man; the other bones did not show obvious osteonecrosis. This work emphasizes the long-term osteopenic effects of low-dose radium, even in the short-lived species 224Ra. It also provides a method of quantifying the osteopenic effect of bone-seeking radionuclides.