Abnormal Bone Mineral Maturation in the Chronic Uremic State

Abstract

A B S T R A C T X-ray diffraction analysis of bone from chronically uremic but nonacidotic rats with normocalcemia and hyperphosphatemia revealed smaller apatite crystals and an increase in the X-ray amorphous mineral fraction when compared to age-matched, pair-fed control animals, indicating less advanced mineral maturation in the uremic animals. Studies in animals with varied degrees of chronic renal insufficiency revealed a progression of the bone crystal maturational defect with advancing uremia. INTRODUCTIONAlthough a causal relationship between chronic renal failure and progressive osteopenia has been well documented by radiographic and histochemical analyses (1, 2), the sequence of physiology and biochemical events that initiate and perpetuate the derangements in skeletal metabolism are still poorly defined. Previous investigations have been concerned primarily with rates of bone mineral (apatite) and matrix (collagen) turnover, under the assumption that the intricate processes of crystal growth and collagen maturation were proceeding in normal fashion. In an earlier study, we demonstrated maturational alterations in bone collagen and mineral metabolism in the experimental uremic state that progressed with advancing uremia, although insignificant alterations in plasma pH, calcium, and bone carbonate content obtained (3). The present study was undertaken to determine whether the apparent collagen maturational defect in the advancing uremic state is associated with compositional and structural alterations of the mineral

Experimental renal osteodystrophy. The response to 25-hydroxycholecalciferol and dicholomethylene diphosphate therapy.

“…The rise in urinary nondialyzable (retentate) polypeptides, containing hydroxyproline, observed during treatment is consistent with this interpretation (Table I) since these fragments largely reflect collagen synthesis (10,11). In a previous communication, alterations in collagen maturation were documented as early as the 2-wk period of experimentally induced uremia (1), well in advance of the inorganic structural alterations of the mineral phase alone (2). Since it is thought that maturation and increased cross-linking of newly synthesized collagen preceeds calcification in hard tissues (3,4), the partial restoration of the crystal maturational sequence may be secondary to the restoration of the bone collagen maturation.…”

“…X-ray diffraction analyses substantiated density gradient measurements suggesting that the relatively "immature" bone tissue of uremic animals was characterized by both increased amounts of X-ray amorphous mineral and less perfect, smallersized, apatite crystallites (2).…”

“…Characterization of the changes in the bone mineral and matrix collagenous protein was accomplished utilizing bromoform-toluene density gradient fractionation (1) as well as X-ray diffraction analysis (2). Total skeletal calcium, phosphorus, and hydroxyproline levels were concomitantly determined, as previously described (1).…”

Failure to detect an amorphous calcium-phosphate solid phase in bone mineral: A radial distribution function study

“…Based on XRD intensity and IR measurements, Harper and Posner [26] and Termine and Posner [11] developed systematic techniques to determine the apparent proportions of ACP and PCHA in mixtures of synthetically prepared components which they and others subsequently used to study bone mineral [11,[28][29][30][31][32]. Initial estimates of the apparent ACP content of normal bone ranged from about 65-70% for young bone and from 35-40% for mature and older bone.…”

“…When these effects were taken into account, the proportion of ACP was revised downward [10,28]: ACP content in young bones to about 50%, mature bones to about 25-30% [10,32,33].…”