Growth changes of collagen cross-linking, calcium, and water content in bone

It has been claimed that the increase in the strength of growing bone is due to increased mineral content. The strength of collagen is based on intermolecular covalent cross-links, and it has also been proposed that cross-link changes increase bone strength. Measurements of the content of calcium, collagen, and water, as well as cross-link analyses, were performed on the tibial cortex of growing dogs. Within the age range studied (8-44 weeks), no changes in calcium content expressed as a percentage of dry bone weight were seen. Collagen content expressed as weight of hydroxyproline per dry bone weight showed a minor reduction during growth. However, water content decreased considerably up to an age of about 25 weeks, which implies a concomitant increase in the amount of bone material. Of the two cross-link main groups, reducible and nonreducible, it is only possible chemically to analyze the reducible. During the final part of the period of growth and mechanical maturation of the bones, the number of reducible cross-links decreases. This indicates a concomitant increase in the more stable nonreducible forms. The possible mechanical relevance of the chemical changes found during growth is discussed.