The composition of recrystallized bone mineral.

Bone mineral and synthetic calcium-deficient carbonate apatite (CDCA), when defined in terms of their respective thermal stabilities and ignition products, are homologous. When heated to 550 degrees, they may have a structure similar to that of the mineral dahllite. When heated to temperatures greater than 550 degrees, CDCA (like bone mineral) losses its structural CO3 and is recrystallized to whitlockite and/or OH-apatite, depending on its stoichiometry.

A chick bone model for evaluating radial bone growth. 1. Effects of vitamin D3 deficiency.

Vitamin D3 is essential for calcification and normal bone development in chicks. In its absence, calcification is reduced but the volume (and mass) of bone increases. In vitamin D3-deficient chicks, this study shows the major defect to be in bone resorption rather than formation. Bone formation measured serially by the apposition of periosteal matrix was normal, whereas bone resorption measured by dissolution at the endosteal surface was dramatically reduced. Bone cells, therefore, would appear to retain their capacity to synthesize a collagenous matrix in the absence of vitamin D3 but lose their capacity to resorb bone. Calcification and its putative dependence on bone resorption (and vitamin D) remain to be elucidated. The vitamin D3-deficient chick provides a convenient and easily quantifiable model in which the morphological and biochemical effects of vitamin D3 can be further studied.

Glutamine metabolism in bone.

Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.

The nature of bone carbonate.

Models of the bone salt and its synthetic analogues have been strenuously, and sometimes emotionally debated since the late nineteenth century. The main protagonist in the drama is the ubiquitous CO3=ion whose role has never been clearly understood. Initially regarded as an essential part of the calcium phosphate crystal complex, it came to be dubiously designated as a separate phase CaCO3, as an adsorbed ion, or even as a mere contaminant. More recent studies provide evidence that the original impression may be more nearly correct. Of particular interest in defining the role of CO3= in bone are the reactions involved in the formation of CO3-apatite under conditions approximating the physiological. These observations suggest that the synthesis of bone mineral involves hydrolysis of an initial acidic calcium phosphate precipitate to octacalcium phosphate, which is then converted to octacalcium phosphate carbonate (OCPC) by virtue of the replacement of PO4 identical to (HPO4=) by CO3=. OCPC satisfies many criteria for a satisfactory definition of the nature of the bone mineral. It can explain its solubility behavior and the intrinsic relationship between PO4 identical to (HPO4=) and CO3=, the normal variations in bone composition, the sequence of events in bone mineral maturation, and the loss of CO3= under normal and pathological conditions.

Inter-relationships of carbonate, phosphate, monohydrogen phosphate, calcium, magnesium and sodium in uraemic bone: comparison of dialysed and non-dialysed patients.

1. Chemical and morphological features of uraemic bone disease were studied by comparison of bone composition in 44 patients with uraemia (12 dialysed and 32 non-dialysed) and 36 control subjects. The significant changes included decreased bone mineral carbonate associated with calcium, a concomitant increase in phosphate, and an increase in magnesium. There was also an increase in osteoid and a reduction in the specific gravity of the compact bone. 2. The most marked changes in bone composition were observed in patients with uraemia of more than 1 year's duration, who had been dialysed. Bone mineral sodium concentrations were not significantly altered in any group. 3. The changes in bone mineral composition appeared to be the result of several simultaneous and/or successive mechanisms: (i) loss of fixed base, calcium carbonate; (ii) replacement of carbonate by phosphate; (iii) the addition of immature bone mineral, which contains high concentrations of phosphate and relatively low concentrations of carbonate. 4. These observations are consistent with earlier views of the bone salt as an indefinite calcium/phosphate/carbonate complex. Variations in bone composition may arise from a reciprocal relationship between phosphate and carbonate. The bone mineral analogue that best explains these variations in bone composition is octacalcium phosphate carbonate [Ca4 (PO4)2(HPO4)x(CO3)1-x,zH2O].