Skeletal changes in multiparous and nulliparous mice fed a nutrient-deficient diet containing cadmium

Female mice were given nutrient-deficient, purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd; the nutrient quality of each was patterned after deficiencies known to be present in food consumed by Japanese women who contracted Itai-Itai disease. One-half of the mice were bred for six consecutive, 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant, virgin controls (NP mice). PL and NP mice were sacrificed at the end of rounds 1, 2, 3, 5, or 6. PL mice taken during the first three rounds were successively pregnant; those taken in later rounds experienced gestation/lactation either four (round 5) or three (round 6) non-successive times. No consistent round-by-round decreases in diet consumption or body weight occurred among NP mice during the 252 days of cadmium exposure, however a significant decrease in femur calcium content (11-17%) was observed in virgin groups exposed to 50 vs. 0.25 ppm Cd. Similar femur decalcification (14-20%) was observed in PL mice, however calcium loss at 50 ppm Cd paralleled decreases in food consumption (24%) and body weight (9-17%). Significant but smaller decreases in the calcium/dry weight (Ca/DW) ratio were found for NP and PL groups consuming 50 ppm dietary Cd. Over the 6-round experiment, exposure to cadmium was found to effect smaller decreases in both femur Ca content and Ca/DW ratio than either consumption of nutrient-deficient diet or multiparous experience. Demineralization results for PL mice provide evidence that the combination of chronic ingestion of cadmium in a nutrient-deficient diet and multiparous activity likely played a role in the etiology of Itai-Itai disease; results for NP mice additionally suggest that decalcification may have been initiated in human females at a time prior to the multiparous and menopausal stages of life.