EFFECTS OF STRONTIUM ON CALCIUM-METABOLISM IN RATS .1. A DISTINCTION BETWEEN THE PHARMACOLOGICAL AND TOXIC DOSES

Strontium at low doses has been used to treat osteoporosis. However, excessive doses can disturb calcium metabolism. The aim of the present study was to determine a dose that does not have any significant toxic effects on calcium contents in bone and calcium metabolism, and, consequently, to distinguish between pharmacological and toxic doses in rats. The rats were divided into a control, 0.05%-Sr, 0.10%-Sr and 0.50%-Sr groups (strontium intake approx. 0, 87.5, 175 and 875 mu mol/day, respectively). All of the rats were pair-fed their respective diets containing various doses of strontium in single metabolic cages from when they were 36 to 63 days old. When the rats were 60 days old, bone formation, bone resorption, calcium balance and intestinal calcium absorption were calculated as calcium metabolic parameters over a 3-day period using calcium balance and kinetic studies. At the age of 64 days, the rats were sacrificed under anesthesia, and the femur and blood were collected. Calcium and strontium levels in the bone and serum were then measured. In the strontium groups that received less than 175 mu mol/day, none of the calcium metabolic parameters were significantly affected. However, the calcium contents in the bone were significantly increased in the group that received 87.5 mu mol/day group. On the other hand, in the group that received the highest dose of strontium (875 mu mol/day), all of the calcium metabolic parameters measured were markedly suppressed. A decrease in calcium level in both the bone and serum was also observed. These results suggest that strontium at doses of less than 175 mu mol per day does not have a toxic effect on calcium contents in bone or calcium metabolism in rats, and a dose of 87.5 mu mol/day may be adopted for future evaluations of the efficacy of strontium in various experimental skeletal diseases.