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Surgically induced uremia in rats II: Osseous PTH-susceptible signaling systems as predictors of bone resorption

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Abstract

Predicting the course of parathormone (PTH)-elicited bone turnover in both humans and experimental rat models with moderate chronic uremia, using only standard clinical chemistry analyses, is often difficult. Consequently, rat bone from 1+2/3 nephrectomized animals, after 230 days of progressive renal failure, was examined for PTH-stimulated adenylate cyclase (AC) and phospholipase C (PLC) activities. Correlations to biological parameters related to the function of bone and kidney were made. Reduced renal function was demonstrated by increased serum creatinine; circulating 1,25 dihydroxyvitamin D3 below detection level; diminished renal PTH-elicited AC activity; and decreased urinary cAMP excretion. PTH-activated renal PL-C was also reduced. However, no significant differences were seen in urine creatinine, calcium, phosphate, and hydroxyproline, nor in serum PTH, alkaline phosphatase, calcium, and phosphate. Notwithstanding, renal osteodystrophy developed as estimated by increased plasticity of the long bones, as well as reduction of the diaphyseal (Dd) and inner femoral midshaft (Di) diameters. Femoral cancellous bone exhibited a substantial elevation of both eroded surface (ES) and osteoid surface (OS) as well as a marked reduction in trabecular bone volume (TBV). Calvarial PTH-activated AC was enhanced, whereas corresponding PL-C was markedly reduced. PTH-enhanced AC correlated positively with ES and negatively with Di, respectively. PTH-enhanced PL-C, however, correlated positively with bone calcium content and negatively with ES. Our results indicate that bone modeling and remodeling are to a large extent related to PTH-elicited signaling systems, and cannot easily be predicted by standard clinical chemistry analyses.

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Authors and Affiliations

  1. Institute of Medical Biochemistry, University of Oslo, Blindern, P.O. Box 1112, N-0317, Oslo, Norway

    G. Jablonski & J. O. Gordeladze

  2. Institute for Surgical Research, The National Hospital, Rikshospitalet, 0027, Oslo, Norway

    G. Jablonski & J. O. Gordeladze

  3. Department of Connective Tissue Biology, Institute of Anatomy, DK-8000, Aarhus C, Denmark

    C. C. Danielsen & L. Mosekilde

Authors
  1. G. Jablonski
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  2. C. C. Danielsen
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  3. L. Mosekilde
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  4. J. O. Gordeladze
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Jablonski, G., Danielsen, C.C., Mosekilde, L. et al. Surgically induced uremia in rats II: Osseous PTH-susceptible signaling systems as predictors of bone resorption. Calcif Tissue Int 55, 281–287 (1994). https://doi.org/10.1007/BF00310407

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  • DOI: https://doi.org/10.1007/BF00310407

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