SKELETAL CHANGES IN MULTIPAROUS AND NULLIPAROUS MICE FED A NUTRIENT-DEFICIENT DIET CONTAINING CADMIUM

Female mice were given nutrient-deficient, purified diets containing e ither 0.25 (environmental), 5, or 50 ppm Cd; the nutrient quality of e ach was patterned after deficiencies known to be present in food consu med by Japanese women who contracted Itai-Itai disease. One-half of th e mice were bred for six consecutive, 42-day rounds of pregnancy/lacta tion (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 successivel y pregnant; those taken in later rounds experienced gestation/lactatio n either four (round 5) or three (round 6) non-successive times. No co nsistent round-by-round decreases in diet consumption or body weight o ccurred 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 decalci fication (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 effe ct smaller decreases in both femur Ca content and Ca/DW ratio than eit her consumption of nutrient-deficient diet or multiparous experience. Demineralization results for PL mice provide evidence that the combina tion 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 decalcificatio n may have been initiated in human females at a time prior to the mult iparous and menopausal stages of life.