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Restoration of Bone Mineralization by Cinacalcet is Associated with a Significant Reduction in Calcitriol-Induced Vascular Calcification in Uremic Rats

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Abstract

The present study investigated to what extent normalization of bone turnover goes along with a reduction of high-dose calcitriol-induced vascular calcifications in uremic rats. Five groups of male Sprague–Dawley rats were studied: sham-operated controls (n = 7), subtotally nephrectomized (SNX) uremic (CRF) animals (n = 12), CRF + calcitriol (vitD) (0.25 μg/kg/day) (n = 12), CRF + vitD + cinacalcet (CIN) (10 mg/kg/day) (n = 12), and CRF + vitD + parathyroidectomy (PTX) (n = 12). Treatment started 2 weeks after SNX and continued for the next 14 weeks. High-dose calcitriol treatment in hyperparathyroid rats went along with the development of distinct vascular calcification, which was significantly reduced by >50 %, in both CIN-treated and PTX animals. Compared to control animals and those of the CRF group, calcitriol treatment either in combination with CIN or PTX or not was associated with a significant increase in bone area comprising ±50 % of the total tissue area. However, whereas excessive woven bone accompanied by a dramatically increased osteoid width/area was seen in the CRF + vitD group, CIN treatment and PTX resulted in significantly reduced serum PTH level, which was accompanied by a distinct reduction of both the bone formation rate and the amount of osteoid. These data indicate that less efficient calcium and phosphorus incorporation in bone inherent to the severe hyperparathyroidism in vitamin D-treated uremic rats goes along with excessive vascular calcification, a process which is partially reversed by CIN treatment in combination with a more efficacious bone mineralization, thus restricting the availability of calcium and phosphate for being deposited in the vessel wall.

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Acknowledgement

The authors thank G. Dams for his technical assistance in providing the bone samples and D. De Weerdt for his help with the graphics. T.D.S. is a recipient of a research grant from the BOF (Special Research Fund) of the University of Antwerp.

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Authors and Affiliations

  1. Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Building T.3, Universiteitplein 1, 2610, Wilrijk, Belgium

    Tineke M. De Schutter, Geert J. Behets, Ellen Neven & Patrick C. D’Haese

  2. Department of Pediatric Nephrology, Center of Cardiovascular Research, Charité Universitätsmedizin, Berlin, Germany

    Susanne Jung & Uwe Querfeld

Authors
  1. Tineke M. De Schutter
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  2. Geert J. Behets
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  3. Susanne Jung
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  4. Ellen Neven
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  5. Patrick C. D’Haese
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  6. Uwe Querfeld
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Corresponding author

Correspondence to Patrick C. D’Haese.

Additional information

The authors have stated that they have no conflict of interest.

Cardiovascular findings of this study have been published in detail in a separate paper (Jung S et al. 2012 J Hypertens 30: doi: 10.1097/HJH.0b013e328357c049, in press).

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De Schutter, T.M., Behets, G.J., Jung, S. et al. Restoration of Bone Mineralization by Cinacalcet is Associated with a Significant Reduction in Calcitriol-Induced Vascular Calcification in Uremic Rats. Calcif Tissue Int 91, 307–315 (2012). https://doi.org/10.1007/s00223-012-9635-0

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  • DOI: https://doi.org/10.1007/s00223-012-9635-0

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