Growth of long bones in renal failure: Roles of hyperparathyroidism, growth hormone and calcitriol

Sanchez, Cheryl P.; Salusky, Isidro B.; Kuizon, Beatriz D.; Abdella, Patricia A.; Jüppner, Harald; Goodman, William G.

doi:10.1046/j.1523-1755.1998.00199.x

Cited by 79 publications

(124 citation statements)

References 22 publications

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“…The animals had free access to drinking water and standard rodent diet containing 23.4% protein, 0.6% calcium, and 0.6% phosphorus (Purina Mills, Indianapolis, IN). After 24 h of acclimatization, 37 rats underwent the first stage of a two-stage 5/6 nephrectomy (Nx) under ketamine and xylazine anesthesia (11). The second stage nephrectomy was completed 7 d later, and seven animals underwent thyroparathyroidectomy (TPTX) at the same time (12).…”

Section: Methodsmentioning

confidence: 99%

“…A group of ten nephrectomized animals received calcitriol (Nx-D) at a daily dose of 50 ng/kg per d by intraperitoneal injection 10 d before sacrifice. The dose and duration of calcitriol therapy was based on an earlier study that showed changes in the growth plate only after 10 d of treatment (11).…”

Section: Methodsmentioning

confidence: 99%

“…Blood was obtained for biochemical determinations for calcium, creatinine, phosphorus, urea nitrogen, and parathyroid hormone (PTH). The proximal tibiae were excised, and tibial length was measured as described previously (11). Bones were decalcified in 15% ethylenediamine tetra-acetic acid in PBS, pH 7.0, at 4°C for approximately 2 wk and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

“…Serum urea nitrogen, creatinine, calcium, and phosphorus levels were measured using standard laboratory methods (11). Serum intact PTH levels were measured using the Rat Intact PTH ELISA assay kit (Immutopics Inc, San Clemente, CA).…”

Section: Serum Biochemical Determinationsmentioning

confidence: 99%

“…In situ hybridization was performed using methods described elsewhere (11,14). 35 S-labeled sense and antisense riboprobes encoding mouse type X collagen, rat PTH/PTHrP receptor, mouse MMP-9/ gelatinase B (provided by Drs.…”

Section: In Situ Hybridization (Radioactive and Nonradioactive)mentioning

confidence: 99%

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Effects of Thyroparathyroidectomy, Exogenous Calcium, and Short-Term Calcitriol Therapy on the Growth Plate in Renal Failure

Sanchez

2003

Journal of the American Society of Nephrology

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Abstract. 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 ϭ 10) and 5/6 nephrectomy (Nx). In the nephrectomized group, animals underwent (a) thyroparathyroidectomy (Nx-TPTX, n ϭ 7), (b) received exogenous calcium (Nx-Calcium, n ϭ 10), (c) received short-term calcitriol therapy (Nx-D, n ϭ 10), or (d) nephrectomized control (NxControl, n ϭ 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. cpsanchez@facstaff.wisc.eduThe prevalence of adynamic bone disease has increased in both adult and pediatric patients with chronic renal failure. The use of large doses of exogenous calcium as phosphate binding agents, aggressive calcitriol therapy, presence of diabetes, and parathyroidectomy may contribute to the development of adynamic bone in these patients (1,2).Adynamic bone is characterized by low to normal serum intact parathyroid hormone levels (PTH), low alkaline phosphatase, and episodes of hypercalcemia (3,4). In the skeleton, there is diminished bone formation rate, a decrease in osteoblast and osteoclast number, and a decline in osteoid formation (4 -6). Linear growth has been reported to decline in prepubertal children who developed adynamic bone during treatment of secondary hyperparathyroidism with high intermittent doses of calcitriol (7). Reductions in tibial length have been demonstrated in nephrectomized rats given exogenous calcium accompanied by reductions in growth (8). Iwasaki et al. (9) have reported that parameters of bone formation were decreased in nephrectomized rats that underwent thyroparathyroidectomy and were given high-calcium diet. In addition, diminution of body weight and inhibition of skeletal growth were reported in young rats with normal renal ...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Serum Biochemical Determinationsmentioning

confidence: 99%

Section: In Situ Hybridization (Radioactive and Nonradioactive)mentioning

confidence: 99%

See 3 more Smart Citations

Effects of Thyroparathyroidectomy, Exogenous Calcium, and Short-Term Calcitriol Therapy on the Growth Plate in Renal Failure

Sanchez

2003

Journal of the American Society of Nephrology

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Expression of osteoclastogenic factor transcripts in osteoblast‐like UMR‐106 cells after exposure to FGF‐23 or FGF‐23 combined with parathyroid hormone

Teerapornpuntakit

Wongdee

Krishnamra

et al. 2016

Cell Biology International

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As a bone-derived hormone, fibroblast growth factor-23 (FGF-23) negatively regulates phosphate and calcium metabolism, while retaining growth-promoting action for mesenchymal cell differentiation. Elevated FGF-23 levels, together with hyperparathyroidism, are often observed in chronic kidney disease, which is associated with impaired bone mineralization and enhanced bone resorption. Although overexpression of osteoblast-derived osteoclastogenic cytokines might contribute to this metabolic bone disease, whether FGF-23 alone and FGF-23 plus parathyroid hormone (PTH) directly modulated the expression of osteoblast-derived osteoclastogenic genes remained elusive. Herein, we demonstrated the direct effects of FGF-23 on proliferation and mRNA expression of osteoblast-specific differentiation and osteoclastogenic markers in rat osteoblast-like UMR-106 cells in the presence or absence of PTH. FGF-23 was found to suppress UMR-106 cell proliferation, while increasing FGF-23 expression, the latter of which suggested the presence of positive feedback regulation of FGF-23 expression in osteoblasts. FGF-23 also upregulated the mRNA expression of osteoblast differentiation markers (e.g., Runx2, osterix, AJ18, Dlx5, alkaline phosphatase, and osteopontin), osteoclastogenic factors (e.g., MCSF, MCP-1, IL-6, and TNF-α), and bone resorption regulators (RANKL and osteoprotegerin). However, combined PTH and FGF-23 exposure did not alter the levels of FGF-23-induced transcripts, suggesting that both hormones had no additive effect. In conclusion, FGF-23 directly suppressed osteoblast proliferation, while inducing osteoclastogenic gene expression in UMR-106 cells, and the FGF-23-induced transcripts were not altered by long-standing PTH exposure.

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Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants

Hauta-alus

Holmlund-Suila

Valkama

et al. 2020

Journal of Bone and Mineral Research

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Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term‐born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 μg/d (group‐10) or 30 μg/d (group‐30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross‐sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2‐year follow‐up (p = 0.041) but not with bone (p = 0.53). Infants in group‐30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] −0.50 [−0.98, −0.01] SD unit, p = 0.044) but not in the group‐10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Growth of long bones in renal failure: Roles of hyperparathyroidism, growth hormone and calcitriol

Abstract: Calcitriol counteracts the trophic actions of growth hormone on epiphyseal growth plate cartilage and modifies chondrocyte differentiation in vivo, and these mechanisms may contribute to disturbances in longitudinal bone growth in renal failure.

Cited by 79 publications

References 22 publications

Effects of Thyroparathyroidectomy, Exogenous Calcium, and Short-Term Calcitriol Therapy on the Growth Plate in Renal Failure

Effects of Thyroparathyroidectomy, Exogenous Calcium, and Short-Term Calcitriol Therapy on the Growth Plate in Renal Failure

Expression of osteoclastogenic factor transcripts in osteoblast‐like UMR‐106 cells after exposure to FGF‐23 or FGF‐23 combined with parathyroid hormone

Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants

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