Effect of Experimental Chronic Renal Insufficiency on Bone Mineral and Collagen Maturation

Abstract

A B S T R A C T The effect of chronic renal disease on bone matrix and mineral maturation was evaluated in rats with experimental renal insufficiency of 2-11 wk duration utilizing bromoform-toluene gradient fractionation of bone powder, pulse labeling experiments with "5Ca and proline-'H differential extraction, an(d X-ray diffraction techniques.Maturation defects in both collagen and minieral (45Ca) metabolism were documented as early as 2 wk after the induction of uremia, when total bone calcium, inorganic phosphate, and hydroxyproline content were unchanged.The maturational defect progressed with advancing uremia despite insignificant changes in plasma pH and calcium, and normal bone carbonate levels.Although circulating levels of 25-hydroxycholecalciferol were significantly lower than normal in the uremic animals, pretreatment with either this vitamin D metabolite or vitamin D3 itself failed to alter the observed changes in skeletal maturation. INTRODUCTIONChronic renal failure is attended by a metabolic acidosis, intestinal malabsorption of amino acids (1) and minerals, alterations in vitamin D3 metabolism as well as increased circulating levels of parathyroid hormone, and uremic toxins such as indoles and guanidines. These biological derangements either singularly or in concert result in a form of osteopenia which because of its varied histological manifestation is termed "renal osteodys-

Abnormal Bone Mineral Maturation in the Chronic Uremic State

“…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 components of skeletal tissue.…”

“…Female Holtzman rats at 6 wk of age were unilaterally nephrectomized with contralateral segmental renal infarction, resulting in an impairment of 7/8 normal kidney function as previously described (3). This ischemic infarction of functioning renal mass persisted during the subsequent 2, 5, or 9-wk period of study.…”

Bone Magnesium Pools in Uremia

“…Magnesium has been shown to stabilize certain amorphous calcium-phosphate deposits and to prevent crystal formation (19). In turn Russell and Avioli have shown that immature bone is increased in uremic rats (20), which could be a consequence of the increased magnesium content. The fact that high magnesium bones required greater heat to induce crystal enlargement further suggests that magnesium may stabilize and determine crystal size in uremic bone.…”

The Regulation of Skeletal Muscle Alanine and Glutamine Formation and Release in Experimental Chronic Uremia in the Rat

“…Chronically uremic rats were produced surgically by unilateral nephrectomy and segmental infarction of the contralateral kidney after ligation of two of the renal arterial branches (26). Supplemental …”