Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2002
Publication Date: 2/1/2003
Citation: Roughead, Z.K., Lukaski, H.C. 2003. Inadequate copper intake reduces serum insulin-like growth factor-1 (IGF-1) and bone strength in rats. Journal of Nutrition. 133:442-448.
Interpretive Summary: Osteoporosis is a common bone disease for which there is no cure. One out of every two women and one out of eight men over age 50 will have an osteoporosis-related fracture in their life time. As we age, the circulating concentration of an important hormone called insulin-like growth factor-1 (IGF-1) also decreases leading to reduced bone formation and gradual bone loss (this is called somatopause). Although we know that food intake regulates serum IGF-1, we do not know how specific nutrients (like copper and zinc) affect this important protein. We designed a study to determine if the amounts of copper and zinc in the diet influence serum IGF-1 concentrations and the quality of bones in growing rats. We fed rats low, medium and high amounts of both minerals. We found that although zinc had the strongest effect on the growth of the animals (as indicated by their body weights), copper was much more influential in determining both serum IGF-1 and also the quality of bones. The long bones in the rats fed the low copper diets were less dense and more fragile that those fed adequate amounts of copper. The vertebrae were also less dense in those fed the low copper diets. We concluded that both adequate amounts of zinc and copper are needed for proper growth. However, relative to zinc, copper is more influential in affecting bone strength. Dietary copper may exert its role in bone health, at least in part, through its effect on serum IGF-1. More research is needed to determine if higher copper intakes protect against bone loss associated with aging.
Technical Abstract: This study examined the effects of graded intakes of zinc (Zn) and copper (Cu) on serum insulin-like growth-factor-1 (IGF-1) concentration and bone quality in growing rats. Using a 3x4 factorial design, weanling, male Sprague Dawley rats were randomly assigned to 12 groups (n=7 per group) and were fed one of 9 modified AIN-93G basal diets with varying amounts of Cu (0.3, 3, and 10 g/g) and Zn (5, 15, 45 g/g) for 6 wk. A group of rats was pair-fed to each low Zn group. While 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 reduced serum IGF-1 and femur breaking strength (by 27% and 14%, respectively, P<0.05) and increased bone IGF-1 concentration (by 62%, P<0.0001). Low Cu intake also increased femur nitrogen, hydroxyproline, hexosamine and calcium concentrations of long bones (P <0.05). Tibia osteocalcin concentration was low at extreme intakes and high at marginal intakes of Cu and Zn (P = 0.003). Femur breaking strength correlated directly with serum IGF-1 (R2 = 0.34, P <0.0001) and inversely with bone IGF-1 concentration (R2 = 0.22, P <0.0001). 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, low and marginal dietary Cu dramatically reduced serum IGF-1 concentration in growing rats. Despite compensatory increases in bone calcium, collagen, hexosamines, and IGF-1 concentrations, bone strength was significantly reduced with low dietary Cu. In the presence of graded intakes of Cu, the effects of dietary Zn were minimal on the long bones, but were more pronounced on spinal bones.