Inadequate copper intake reduces serum insulin-like growth factor-I and bone strength in growing rats fed graded amounts of copper and zinc

This study examined the effects of graded intakes of zinc (Zn) and copper (Cu) on serum insulin-like growth-factor-I (IGF-I) concentration and bone quality in growing rats. Using a 3 X 4 factorial design, weanling male Sprague-Dawley rats were randomly assigned to 12 groups (n = 7 per group) and were fed one of nine modified AIN-93G basal diets with varying amounts of Cu (0.3, 3 and 10 mug/g) and Zn (5, 15 and 45 mug/g) for 6 wk. A group of rats was pair-fed to each low Zn group. Although dietary Zn mainly influenced body weights (P < 0.0001), dietary Cu was the main determinant of most of the variables related to bone quality. Low Cu intake reduced serum IGF-I and femur breaking force and ultimate stress (by 27, 14 and 7%, respectively; P < 0.05) and increased bone IGF-I concentration (by 62%; P < 0.0001). Low Cu intake also increased femur nitrogen, hydroxyproline, hexosamine and calcium (Ca) concentrations of long bones (P < 0.05). Lumbar vertebrae dry weight and density were the lowest in the rats fed the low Cu diets (P < 0.001) and were higher in the rats fed high amounts of both Cu and Zn (P < 0.01). In summary, growing rats fed low and marginal Cu had lower serum IGF-I than those fed high dietary Cu. Bone strength was also reduced with low dietary Cu, despite compensatory changes in the bone matrix. In the presence of graded intakes of Cu, the effects of low dietary Zn were more pronounced on the spinal bones than the long bones.