Background Low bone turnover despite normal parathyroid hormone (PTH) conce
ntrations has been found in many patients with end-stage renal failure. Hyp
oresponsiveness to the calcaemic action is also a known feature of uraemia.
Hyporesponsiveness of bone surface cells involved in bone modelling has no
t been demonstrated to date. It was the purpose of this study using a rat m
odel of moderate renal failure to investigate whether doses of PTH and calc
itriol that reverse the effect of parathyroidectomy on calcaemia also norma
lize bone surface cell activity.
Materials and methods Sham-operated pair-fed male Sprague-Dawley rats were
compared with subtotally nephrectomized (SNX), parathyroidectomized (PTX) r
ats 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 measu
rements were carried out in the vertebral body (L5).
Results In SNX/PTX animals, calcitriol + 1,34 rat PTH caused a modest incre
ase 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 nor normalized by PTH + calcitriol (3.3 +/- 3)
. In contrast, osteoblast surface per cent and osteoid surface per cent wer
e increased over values in sham-operated rats; as a result, co-administrati
on of calcitriol and 1,34 rat PTH caused a highly significant increase in f
ractional bone volume (BV/TV).
Conclusions The results show that administration of PTH and calcitriol in d
oses that raise serum calcium fails to normalize the percentage of osteocla
st surface, but was effective in raising osteoblast number and osteoblast v
olume in experimental renal failure. The results argue for abnormal respons
e of bone cells to calcium-regulating hormones and/or the action of factors
other than calcium regulatory hormones in the genesis of skeletal abnormal
ities of renal failure.