Effects of thyroparathyroidectomy, exogenous calcium, and short-term calcitriol therapy on the growth plate in renal failure.
Several factors have been implicated in the development of adynamic bone, including the use of calcium-containing phosphate binding agents, aggressive calcitriol therapy, and parathyroidectomy. To evaluate the effects of these interventions on the growth plate, weanling rats underwent sham nephrectomy (Control, n = 10) and 5/6 nephrectomy (Nx). In the nephrectomized group, animals underwent (a) thyroparathyroidectomy (Nx-TPTX, n = 7), (b) received exogenous calcium (Nx-Calcium, n = 10), (c) received short-term calcitriol therapy (Nx-D, n = 10), or (d) nephrectomized control (Nx-Control, n = 10). Higher serum calcium and lower PTH levels were demonstrated in Nx-Calcium and Nx-D animals. A decline in growth was demonstrated in Nx-Calcium and Nx-TPTX accompanied by shorter tibial lengths. The width of the growth plate was wider in Nx-Calcium animals due to an increase in the width of the hypertrophic zone and a decrease in the proliferative zone; these changes were accompanied by an impairment of chondroclastic resorption, lower gelatinase B/MMP-9 activity, decline in insulin-like growth factor-I (IGF-I) receptor, and lower histone-4 mRNA expression. Such findings in the growth plate, may partially contribute to the diminution of growth in these animals. Although growth was impaired in the Nx-TPTX animals, there were no significant changes demonstrated in the growth plate cartilage. Histone-4 transcripts, IGF-I receptor expression, and histochemical staining for chondroclasts were decreased in Nx-D animals. Thus, treatments used in the management of secondary hyperparathyroidism in renal failure have diverse effects on the growth plate of the young skeleton, and concurrent use of these interventions needs further evaluation.
Sanchez
Cheryl P
CP
Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. cpsanchez@facstaff.wisc.edu
He
Yu-Zhu
YZ
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000008:administration & dosage*; D002455:Cell Division; D019902:Chondrocytes / Q000473:pathology; D004334:Drug Administration Schedule; D006132:Growth Plate / Q000187:drug effects* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009392:Nephrectomy; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000473:pathology / Q000628:therapy*; D000071681:Tartrate-Resistant Acid Phosphatase; D013965:Thyroidectomy
D002120:Calcium Channel Agonists; D007527:Isoenzymes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D020780:Matrix Metalloproteinase 9; D002117:Calcitriol; D002118:Calcium