Realizing that the physiology and biochemistry of bone and the nutritional role of vitamin D are important to orthopedists nutritionists, other clinicians, and to basic scientists, we have established the following overall objectives and long-term goals for the proposed work: (1) to gain a better understanding of the regulatory factors involved in the formation and stabilization of the macromolecular matrix of bone; (2) to ascertain and understand the mechanisms whereby pathogenic disorders alter the quantitative relationship of the intermolecular covalent structural crosslinks of bone collagen; and (3) to gain insight into and compare the molecular architectures of normal and patholoic bone collagen. Basic research into these phenomena will lead to an understanding of the structure-function relationship of mineralized matrices. Rates of turnover and biosynthesis of soft and hard tissue collagen will be compared between normal and vitamin D-deficient chicks. Rachitic bone collagen will be prepared, and the analysis, distribution and loci of the intermolecular crosslinks will be detemined from amino acid composition and sequence of CNBr and smaller peptides prepared from specific enzymic digests. The amounts of NaBH4-reducible stable imines and their location in collagen will be determined by various chemical methods. The locus of all the hydroxylysines partaking in crosslink formation will be identified. Abberrations noted may elucidate and provide insight into the structure-function relationship of bone collagen. The ultimate goal of such a study is to disclose specific structural and functional alterations so that their expressson in biochemical and molecular terms may be used in formulating rational diagnostic and therapeutic procedures in disease states involving bone.