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Vitamin D3 analogs and salmon calcitonin partially reverse the development of renal osteodystrophy in rats

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Abstract

We have previously established an uremic rat model which is suitable for investigating the effect of various treatment modalities on the progression of renal osteodystrophy [1]. Four months subsequent to 5/6 nephrectomy, animals were treated three times a week for 3 months with either vehicle, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 1,25(OH)2D3+24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25(OH)2D3+calcitonin (CT), or 1,25(OH)2D3+ 24,25(OH)2D3+CT. At termination of the study, clinical chemistry, chemical composition, and mechanical properties of femurs, calvarial parathyroid hormone (PTH)-elicited adenylate cyclase (AC), and phospholipase C (PL-C) activities, femoral cross-sectional area, and bone histomorphometry were analyzed. The main findings were that 1,25(OH)2D3±24,25(OH)2D3 treatment enhanced elasticity as well as time to fracture at the femoral metaphysis. CT potentiated the increase in elasticity obtained by 1,25(OH)2D3±24,25(OH)2D3 treatment. Only 24,25(OH)2D3 administration rectified the supernormal PTH-stimulated uremic bone AC, and only 1,25(OH)2D3 medication normalized the diminished CT-elicited AC. The obliterated uremic bone PTH-sensitive PL-C was fully normalized by all drug regimens. Femoral shaft inner zone diameter was enhanced by uremia, however, all drug treatments normalized it. Ditto effect was registered with either drug treatment on the subnormal outer and inner zone widths. Histomorphometrical analyses showed that 1,25(OH)2D3 administration reduced both eroded and osteoid surfaces. Most prominently, adjuvant 24,25(OH)2D3 or CT administration potentiated the beneficial effect of 1,25(OH)2D3 on fibrosis and osteomalacia. We assert that vitamin D3 treatment markedly reverses the development of renal osteodystrophy, and CT potentiates the effect of vitamin D3.

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Authors and Affiliations

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

    G. Jablonski, B. M. Mortensen, K. H. Klem & J. O. Gordeladze

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

    G. Jablonski, B. M. Mortensen & J. O. Gordeladze

  3. Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark

    L. Mosekilde & C. C. Danielsen

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  1. G. Jablonski
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  6. J. O. Gordeladze
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Jablonski, G., Mortensen, B.M., Klem, K.H. et al. Vitamin D3 analogs and salmon calcitonin partially reverse the development of renal osteodystrophy in rats. Calcif Tissue Int 57, 385–391 (1995). https://doi.org/10.1007/BF00302075

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