Uncoupling between Bone Formation and Resorption in Ovariectomized Rats with Chronic Cadmium Exposure

Abstract

Osteoporosis, osteomalacia, and pathological fractures are characteristic features of Itai–Itai disease. The mechanisms of bone damage caused by cadmium (Cd) exposure have not been fully clarified. We investigated skeletal changes in ovariectomized rats with chronic Cd exposure, using bone histomorphometry and mechanical tests. Female Sprague–Dawley rats at the age of 8 weeks were ovariectomized. Eight weeks after ovariectomy, the rats were divided into two groups: Cd–OVX group (n = 15), ovariectomized rats given cadmium chloride (CdCl2, 0.18 mg/rat) ip three times a week for 28 weeks; Cont–OVX group (n = 10), ovariectomized rats given distilled water alone for 28 weeks. Cd–OVX rats had a significant increase in serum concentration of intact osteocalcine and showed numerical but not significant increase in urinary excretion of deoxypyridinoline despite a significant decrease in glomerular filtration rate to 40% of the value in Cont–OVX rats. Bone mineral content (BMC) and density were significantly decreased in both the lumbar vertebral body and femur of Cd–OVX rats. Ultimate compressive load in the lumbar body and bending load in the midfemur were significantly lower in Cd–OVX rats than in Cont–OVX rats but the differences were not demonstrated when the values were corrected for BMC. Structural moduli in the lumbar vertebral body and the midfemur were not different between the two groups. Cd–OVX rats showed significant decreases in the trabecular bone volume and trabecular number with increased values in the indices of bone formation and resorption in the lumbar vertebral body cancellous bone in comparison with Cont–OVX rats. In the midfemur, Cd–OVX rats had significantly smaller cortical bone area than Cont–OVX rats but the moment of inertia was identical between the two groups. The indices of bone formation and resorption at endocortical surface of the midfemur were significantly increased in Cd–OVX rats over those in Cont–OVX rats, whereas the indices of bone formation at the periosteal surface were not different between the two groups. These data suggested that chronic Cd exposure exacerbated the uncoupling between bone formation and resorption in ovariectomized rats, which resulted in the osteopenia, structural changes of the bone, and decreased mechanical strength in ovariectomized rats with chronic Cd exposure.