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The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

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Abstract

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

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Acknowledgements

This study received financial support in the form of grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant 01/01789-0) and from Genzyme. The authors acknowledge the assistance provided by Jefferson D. Boyles and Cristina Siqueira in the translation and editing of the text as well as the technical assistance provided by Rosimeire Aparecida Bizerra. We also thank Dr. Susan C. Schiavi (Genzyme) for supplying the rat PTH vials.

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Authors and Affiliations

  1. Nephrology Division, Medical School of University of São Paulo, São Paulo, Brazil

    Daniella G. Batista, Kátia R. Neves, Fabiana G. Graciolli, Luciene M. dos Reis, Rafael G. Graciolli, Wagner V. Dominguez, Carolina L. Neves, Andrea O. Magalhães, Melani R. Custódio, Rosa M. Moysés & Vanda Jorgetti

  2. Laboratório de Fisiopatologia Renal (LIM-16), Av. Dr. Arnaldo, 455, sala 3342, 01246-903, São Paulo, SP, Brazil

    Vanda Jorgetti

Authors
  1. Daniella G. Batista
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  2. Kátia R. Neves
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  3. Fabiana G. Graciolli
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  4. Luciene M. dos Reis
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  5. Rafael G. Graciolli
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  6. Wagner V. Dominguez
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  7. Carolina L. Neves
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  8. Andrea O. Magalhães
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  9. Melani R. Custódio
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  10. Rosa M. Moysés
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  11. Vanda Jorgetti
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Corresponding author

Correspondence to Vanda Jorgetti.

Additional information

V. Jorgetti has received remuneration from Genzyme and has a consultant/advisory role at Genzyme and Abbott. All other authors have stated that they have no conflict of interest.

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Batista, D.G., Neves, K.R., Graciolli, F.G. et al. The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances. Calcif Tissue Int 87, 60–67 (2010). https://doi.org/10.1007/s00223-010-9367-y

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  • DOI: https://doi.org/10.1007/s00223-010-9367-y

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