Cadmium-induced bone loss: Increased susceptibility in females

Abstract

An overview is presented of studies on effects of Cd on (1) female mice during pregnancy and lactation and after ovariectomy and (2) bone organ/cell culture systems. The gastrointestinal absorption of Cd increased two- to threefold in mouse dams during pregnancy and lactation, with both the kidneys and duodenum of the dam showing striking increases in Cd deposition. Dietary Cd at 5 or 50 μg g⁻¹ caused a dose-dependent decrease in femur Ca content in multiparous mouse dams but not in nonpregnant controls. In addition, dietary Cd at 50 μg g⁻¹ significantly increased the loss of bone mineral that occurs normally in mice after removal of the ovaries. In cultures of fetal rat limb bones prelabeled with ⁴⁵Ca, Cd at 10 nM (1 ng g⁻¹) caused a release of 70% of the ⁴⁵Ca, similar to the release caused by 10 nM parathyroid hormone. This level of Cd also caused a fivefold increase in the number of multinucleated osteoclast-like cells formed during in vitro incubation of progenitor-enriched mononuclear bone marrow cells. These results support the view that Cd exposure contributed to the pathogenesis of Itai-Itai disease among multiparous, postmenopausal women in Japan and provide evidence that Cd may act directly on bone.