Uncoupling between bone formation and resorption in ovariectomized rats with chronic cadmium exposure

Osteoporosis, osteomalacia, and pathological fractures are characteristic f eatures of Itai-Itai disease. The mechanisms of bone damage caused by cadmi um (Cd) exposure have not been fully clarified. We investigated skeletal ch anges in ovariectomized rats with chronic Cd exposure, using bone histomorp hometry and mechanical tests. Female Sprague-Dawley rats at the age of 8 we eks were ovariectomized. Eight weeks after ovariectomy, the rats were divid ed into two groups: Cd-OVX group (n = 15), ovariectomized rats given cadmiu m chloride (CdCl2, 0.18 mg/rat) ip three times a week for 28 weeks; Cont-OV X group (n = 10), ovariectomized rats given distilled water alone for 28 we eks. Cd-OVX rats had a significant increase in serum concentration of intac t osteocalcine and showed numerical but not significant increase in urinary excretion of deoxypyridinoline despite a significant decrease in glomerula r filtration rate to 40% of the value in Cont-OVX rats. Bone mineral conten t (BMC) and density were significantly decreased in both the lumbar vertebr al body and femur of Cd-OVX rats. Ultimate compressive load in the lumbar b ody and bending load in the midfemur were significantly lower in Cd-OVX rat s than in Cont-OVX rats but the differences were not demonstrated when the values were corrected for BMC. Structural moduli in the lumbar vertebral bo dy and the midfemur were not different between the two groups. Cd-OVX rats showed significant decreases in the trabecular bone volume and trabecular n umber with increased values in the indices of bone formation and resorption in the lumbar vertebral body cancellous bone in comparison with Cont-OVX r ats. In the midfemur, Cd-OVX rats had significantly smaller cortical bone a rea than Cont-OVX rats but the moment of inertia was identical between the two groups. The indices of bone formation and resorption at endocortical su rface of the midfemur were significantly increased in Cd-OVX rats over thos e in Cont-OVX rats, whereas the indices of bone formation at the periosteal surface were not different between the two groups. These data suggested th at chronic Cd exposure exacerbated the uncoupling between bone formation an d resorption in ovariectomized rats, which resulted in the osteopenia, stru ctural changes of the bone, and decreased mechanical strength in ovariectom ized rats with chronic Cd exposure, (C) 2000 academic Press.