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Updated: Aug 24, 2026
Generation of Hypoparathyroid Rats via Carbon-Nanoparticle-Assisted Parathyroidectomy
Published on: July 14, 2023
Bone elongation in rats with renal failure and mild or advanced secondary hyperparathyroidism
Cheryl P Sanchez1, Yu-Zhu He, Ellen Leiferman
1Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. cpsanchez@wisc.edu
Insights
Growth impairment in chronic kidney disease is exacerbated by severe secondary hyperparathyroidism. This study in rats shows advanced hyperparathyroidism worsens growth plate changes and insulin-like growth factor-I (IGF-I) signaling.
Area of Science:
- Pediatric Endocrinology
- Nephrology
- Skeletal Biology
Background:
- Chronic renal failure (CRF) in children can lead to growth impairment, potentially due to insulin-like growth factor-I (IGF-I) resistance caused by altered IGF binding proteins.
- Changes in the growth plate in CRF are documented, but few studies have compared endochondral ossification markers in CRF with varying degrees of secondary hyperparathyroidism.
Purpose of the Study:
- To investigate the impact of advanced secondary hyperparathyroidism on growth plate alterations and endochondral bone formation markers in a rat model of chronic renal failure.
- To compare these changes with those in renal failure without induced hyperparathyroidism.
Main Methods:
- Forty-six rats underwent 5/6 nephrectomy (Nx). Rats were fed either a standard diet (Nx-control) or a high-phosphorus diet to induce advanced secondary hyperparathyroidism (Nx-phosphorus) for four weeks.
- Tibia sections were analyzed using histomorphometry, immunohistochemistry, and in situ hybridization to assess markers of endochondral bone formation.
Main Results:
- Nephrectomized rats showed reduced weight gain and tibial length. The Nx-phosphorus group exhibited higher parathyroid hormone (PTH) and phosphorus levels, and lower calcium levels.
- The growth plate was significantly narrower in the Nx-phosphorus group, with reduced proliferative and hypertrophic zones. IGF-I protein and IGF binding protein-3 staining decreased in both Nx groups, with a more pronounced decline in IGF-I in the Nx-phosphorus group.
- Parathyroid hormone/PTH-related peptide receptor (PTHrP) mRNA and tartrate-resistant acid phosphatase (TRAP) staining increased only in the Nx-phosphorus group.
Conclusions:
- Advanced secondary hyperparathyroidism significantly worsens growth plate abnormalities and alters endochondral ossification markers in chronic renal failure.
- The severity of secondary hyperparathyroidism may be a critical factor in the growth impairment observed in children with chronic kidney disease.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
The growth impairment in renal failure may be worsened by the severity of secondary hyperparathyroidism.
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