Comparison of peripheral bone and body axis skeleton in a rat model of mild-to-moderate renal failure in the presence of physiological serum levels of calcitropic hormones.
The skeleton is characterized by anatomic heterogeneity of metabolic turnover. Site-dependent differences in hormonal effects seem likely. Hyporesponsiveness of osteoclasts to parathyroid hormone (PTH) and probably calcitriol was recently demonstrated in the fifth lumbar vertebra of a rat model with moderate renal failure. We compared histomorphometric findings of the tibial head to these data. Histomorphometric measurements were carried out in sections of the right tibial head of pair-fed male Sprague-Dawley rats. Subtotally nephrectomized (SNx), parathyroidectomized (PTx), rats, which received either solvent or rat PTH(1-34) (100 ng/kg per hour) + calcitriol (5 pmol/kg per hour) via osmotic minipumps were compared with sham-operated controls. Results were compared with data from the fifth lumbar vertebra reported recently. Osteoclast numerical density and osteoclast surface density were lower in the tibial head and the lumbar vertebra of solvent-treated SNxPTx rats than in sham-operated controls (p < 0.05), and could not be returned to normal by the substitution of PTH + calcitriol (p < 0.05). On the other hand, there were differences between interventional effects on the tibial head and on the lumbar vertebra concerning parameters describing osteoblasts and trabecular bone volume. In the tibial head, osteoblast surface density was nearly unchanged in both interventions. Nevertheless, bone volume increased after SNxPTx without substitution of PTH + calcitriol (p < 0.05), and no further changes occurred after hormonal replacement. In contrast, osteoblast surface density in the lumbar vertebra was decreased slightly compared with values in sham-operated rats; a clear but nonsignificant increase occurred after the administration of calcitropic hormones. This was accompanied by unchanged trabecular bone volume after SNxPTx. Hormonal replacement, however, caused an increase in trabecular bone volume (p < 0.05), which represents an anabolic effect, which contrasts with findings from the tibial head. The different interventional effects on the lumbar spine and on peripheral bone, regarding the parameters reflecting the condition of osteoblasts, may be intrinsic to the uremic syndrome itself as well as to dissimilar growth manner, function, and mechanical requirements. The findings substantiate the site dependence of bone surface cell metabolism in renal failure and should be the subject of further study. Corresponding results with regard to bone resorption argue for a bone-site-independent, diminished response of osteoclasts to calcitropic hormones.
Freesmeyer
M G
MG
Department of Internal Medicine IV, Friedrich-Schiller-University, Jena, Germany.
Abendroth
K
K
Faldum
A
A
Krauss
C
C
Stein
G
G
D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology*; D008297:Male; D009392:Nephrectomy; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D016105:Parathyroidectomy; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000097:blood / Q000473:pathology*; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D013977:Tibia / Q000473:pathology*; D014511:Uremia / Q000097:blood / Q000473:pathology
D010446:Peptide Fragments; D019379:Teriparatide; D002117:Calcitriol; C035748:parathyroid hormone (1-34)amide