|Abstract / Summary|
The Effects of Zinc Ions on Bone Growth, Modeling and Remodeling This Ph.D.-thesis is based on three original papers investigating the effects of zinc on bone modelling and remodelling. Aims I. Investigation of bone quality after alimentary zinc depletion and supplementation in an animal model of intact, growing rats. A biomechanical study. Paper I. II. A histological description of bone changes and the amount and localization of zinc ions following alimentary zinc depletion and supplementation in an animal model of intact growing rats. A histological study. Paper II. III. The effects of alimentary zinc depletion and supplementation on fracture healing in an animal model with a standardized closed fracture. A biomechanical study. Paper III. Methods Forty-five 4 weeks-old, male Wistar rats were used for the investigation in paper I and II, and eighty, 12-weeks-old male rats were used in the fracture study (paper III). The animals were housed in pairs in metal-free cages in rooms with controlled temperature and a 12:12 h light/dark cycle. They were given free access to a semisynthetic diet with different amounts of zinc added and distilled water. All animals were sacrified and both hindlimbs were investigated by use of histology and biomechanical testing. Results Paper I and II • Alimentary zinc supplementation in growing rats has a potent anabolic effect. Both the body weight and the length of the femora increased dose-dependently. • Zinc induced a significant increase in bone strength in growing rats at all investigated sites. • Zinc influenced bone strength in growing rats in a dose-dependent manner, except at the distal femoral metaphysis, where there was no significant difference between the two groups of rats fed with zinc-supplemented diet. • Static hisomorphometry showed that zinc exerted its main effect on growing rats on the periosteal envelope. • Alimentary zinc supply to growing rats resulted in an increase in the height of the total growth plate in a dose-dependent manner. • Based on the modified autometallographic Timm sulphide silver method (AMG), zinc ions are demonstrated as present in osteoid bone, joint cartilage and synovial membrane. In other words at the site of bone formation as a requisite for complete calcification. • At ultrastructural levels (electron microscopy) AMG-stained zinc ions were demonstrated at the initial site of calcification in, what we believe to be, matrix vesicles in the unmineralized bone matrix. • Zinc concentration in bone in growing rats were significantly decreased in zinc depleted rats. Paper III • The growth in growing rats suffering a fracture was not influenced by the zinc content of the daily diets. • The time of fracture healing in growing rats was not influenced by the additional administration of zinc to the daily diets and no histological differences were found. • Biomechanical testing revealed a significant zinc-induced effect on the maximum load values of the fractsite after 56 days of healing in growing rats.