Physiological doses of calcium regulatory hormones do not normalize bone cells in uraemic rats

A. Szabó, M. G. Freesmeyer, K. Abendroth, G. Stein, L. Rosivall, A. El-Shakmak, E. Ritz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background. Low bone turnover despite normal parathyroid hormone (PTH) concentrations has been found in many patients with end-stage renal failure. Hyporesponsiveness to the calcaemic action is also a known feature of uraemia. Hyporesponsiveness of bone surface cells involved in bone modelling has not been demonstrated to date. It was the purpose of this study using a rat model of moderate renal failure to investigate whether doses of PTH and calcitriol that reverse the effect of parathyroidectomy on calcaemia also normalize bone surface cell activity. Materials and methods. Sham-operated pair-fed male Spraque-Dawley rats were compared with subtotally nephrectomized (SNX), parathyroidectomized (PTX) rats that received either solvent or calcitriol (5 pmol kg-1 h-1) + 1,34 rat PTH (100 ng kg-1 h-1) by osmotic minipump. Histomorphometric measurements were carried out in the vertebral body (L5). Results. In SNX/PTX animals, calcitriol + 1,34 rat PTH caused a modest increase in serum calcium (S-Ca) within the normal range. Osteoclast surface per cent was significantly lower in solvent-treated SNX/PTX rats than in sham-operated controls [3.7 ± 2.8 osteoclast surface/bone surface (OcS/BS%) vs. 6.3 ± 3.9], and this was not normalized by PTH + calcitriol (3.3 ± 3). In contrast, osteoblast surface per cent and osteoid surface per cent were increased over values in sham-operated rats; as a result, co-administration of calcitriol and 1,34 rat PTH caused a highly significant increase in fractional bone volume (BV/TV). Conclusions. The results show that administration of PTH and calcitriol in doses that raise serum calcium fails to normalize the percentage of osteoclast surface, but was effective in raising osteoblast number and osteoblast volume in experimental renal failure. The results argue for abnormal response of bone cells to calcium-regulating hormones and/or the action of factors other than calcium regulatory hormones in the genesis of skeletal abnormalities of renal failure.

Original languageEnglish
Pages (from-to)529-535
Number of pages7
JournalEuropean Journal of Clinical Investigation
Volume29
Issue number6
DOIs
Publication statusPublished - 1999

Keywords

  • Calcitriol
  • Parathyroid hormone
  • Parathyroid hormone resistance
  • Secondary hyperparathyroidism
  • Uraemia

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

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