The proposed research is designed to determine the chemical and structural changes which take place both in the molecular configurations of bone mineral components and in their interaction with the organic matrix during nucleation, maturation and aging. These changes occurring in bone as a tissue and as an organ influence the qualify of bone fabric as a material (mechanical support) and as an ion reservoir (physiological role). The delineation of those changes in normal tissue will provide a baseline to assess the effect on the qualities of the bone fabric resulting from pathological conditions including osteomalacia and rickets, osteoporosis and renal osteodystrophy. Our study will make extensive use of density fractionation of bone, which yields tissue samples which are relatively homogeneous with respect to the stage of maturation. The availability of such samples avoids the problem of major portions of the tissue obscuring the properties of minor fractions, and allows study of the bone mineral from the earliest solid deposits, through progressively increasing degrees of mineralization and maturation, to the most mature stages reached during aging. We will also carefully dissect and study tissues which have been shown to contain exclusively the earliest solid mineral deposits in developing bone, and prepare newly-formed bone under controlled conditions in bone organ culture. We will study the tissue-age differentiated bone mineral by x-ray diffraction, including radial distribution function analysis, nuclear magnetic resonance spectroscopy (which is uniquely capable of elucidating the nature of the important acid-phosphate constituent of bone mineral) and chemical composition analyses. The results of these studies will be integrated to provide a detailed characterization of the major structural and composition features of the initial mineral deposited, and the changes which take place in the mineral component during further development, maturation and aging.
