Bone elongation in rats with renal failure and mild or advanced secondary hyperparathyroidism

Abstract

Impairment of growth in children with chronic renal failure may be due, in part to the insensitivity to the actions of growth hormone by insulin-like growth factor-I (IGF-I) because of accumulations of IGF binding proteins. There are a few studies describing the changes that occur in the growth plate in renal failure. None of these studies has simultaneously compared the modifications in the expression of selected markers of endochondral bone formation in renal failure with mild or advanced secondary hyperparathyroidism. Forty-six rats that underwent 5/6 nephrectomy (Nx) were fed either standard rodent diet (Nx-control) or high phosphorus diet to induce advanced secondary hyperparathyroidism (Nx-phosphorus) for 4 weeks. Sections of the tibia were obtained for growth plate histomorphometry, immunohistochemistry studies, and in situ hybridization experiments for selected markers of endochondral bone formation. Weight gain, gain in length, and tibial length were less in Nx animals. Serum parathyroid hormone (PTH) and phosphorus levels were higher and serum calcium levels were lower in the Nx-phosphorus group. The width of the growth plate was much shorter in the Nx-phosphorus group due to a decrease in both proliferative and hypertrophic zones. IGF-I protein and IGF binding protein-3 staining were diminished in both Nx groups without changes in the IGF-I receptor expression; the decline in IGF-I protein expression was much lower in the Nx-phosphorus group. PTH/PTH receptor protein (PTHrP) receptor mRNA transcripts decline and tartrate-resistant acid phosphastase (TRAP) staining increased only in the Nx-phosphorus group. The growth impairment in renal failure may be worsened by the severity of secondary hyperparathyroidism.