Renal Osteodystrophy: New Insights in Pathophysiology and Treatment Modalities with Special Emphasis on the Insulin-Like Growth Factor System

Jehle, Peter; Jehle, Daniela R.; Mohan, Subburaman; Keller, Frieder

doi:10.1159/000045046

Cited by 19 publications

(24 citation statements)

References 167 publications

(180 reference statements)

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“…IGF-1 and -2 are important regulators of bone metabolism. Bone cell types capable of synthesizing IGF-1 are osteoblasts and stimulate proliferation, differentiation and matrix synthesis in those cells [5, 13]. It appears that IGFs act on bone cells not only by paracrine but also by endocrine pathways, suggesting that circulating IGFs may be of important for the regulation of bone metabolism [14].…”

Section: Discussionmentioning

confidence: 99%

“…IGFBP-3 and -5) and negative manner (e.g. IGFBP 1, 2 and 4) in bone cells [5, 15]. IGFBP-3 is positively regulated by growth hormone and potentiates IGF action under most conditions [5].…”

Section: Discussionmentioning

confidence: 99%

“…The anabolic effect of PTH is mediated in part by the ability of PTH to stimulate the production of IGF-1 [4]. It has been speculated that IGFs and TGF-β are released during osteoclastic bone resorption to initiate the bone formation phase of the remodeling cycle [5]. The importance of the IGF system as a key regulator of bone formation is demonstrated by the finding that approximately 50% of basal bone cell proliferation could be blocked by inhibiting the actions of IGFs produced endogenously by bone cells in serum-free culture [6].…”

Section: Introductionmentioning

confidence: 99%

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Changes in Bone Mineral Density, Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 in Kidney Transplant Recipients

Söylemezoğlu

Derici²,

Arınsoy³

et al. 2002

Nephron

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Background: Osteopenia is a major complication of renal transplantation (RTx). This cross-sectional and longitudinal study was planned to better define long-term bone status and relationship to IGF system components. Methods: Serial measurements of bone mineral density (BMD) and serum markers were performed in 30 patients prior to RTx and at 6 and 12 months following RTx. Serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), vitamin D, and intact parathyroid hormone (iPTH) were measured. Results: Serum creatinine, phosphate, alkaline phosphatase and osteocalcine levels decreased, serum calcium levels increased and serum iPTH levels did not change significantly after transplantation. The mean BMD of the vertebrae was 0.97 ± 0.22 g/cm² at the time of RTx, 0.87 ± 0.21 g/cm² 6 months post-RTx (p < 0.05), and 0.81 ± 0.21 g/cm² 12 months post-RTx (p < 0.05). Femur BMD also declined from 0.79 ± 0.16 to 0.72 ± 14 g/cm² at 12 months (p < 0.05). There was a significant increase in the IGF-1 and a significant reduction in the IGFBP-3 concentrations at 6 months post-RTx (p < 0.05). Significant correlations between serum IGF-1 concentrations and vitamin D concentrations were noted only at 6 months. There was no significant correlation between the BMD and serum IGF system. Conclusions: These results demonstrate a significant loss of BMD after RTx. The circulating levels of IGF-1 and IGFBP-3 stimulated by the reduction in BMD and IGF-1 secretion are increased in order to restore bone formation.

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Section: Discussionmentioning

confidence: 99%

“…IGFBP-3 and -5) and negative manner (e.g. IGFBP 1, 2 and 4) in bone cells [5, 15]. IGFBP-3 is positively regulated by growth hormone and potentiates IGF action under most conditions [5].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in Bone Mineral Density, Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 in Kidney Transplant Recipients

Söylemezoğlu

Derici²,

Arınsoy³

et al. 2002

Nephron

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“…reduced tyrosine kinase activity) may further account for reduced IGF effects on tissues [43]. Previous studies have shown that CRF patients with high PTH levels exhibit increased bone turnover [3, 4, 5]and a diminished bone mineral density [8]. We anticipated sera from CRF patients with PTH >300 pg/ml to contain higher levels of IGFs than control subjects such that IGF-induced bone formation could compensate for the elevated bone resorption caused by elevated PTH levels in these subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Children with CRF exhibit poor linear growth [1, 2]. In addition, CRF in adults is often associated with secondary hyperparathyroidism and increased bone turnover, a condition called hyperparathyroid bone disease (HBD) [3, 4, 5]. Patients with HBD sometimes show severe osteopenia and/or pathological fractures [6 , 7].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of IGF System Component Levels and Mitogenic Activity of Uremic Serum on Normal Human Osteoblasts

Wagner

Stracke²,

Jehle³

et al. 2000

Nephron

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To test the hypothesis that impairment in bone formation in renal osteodystrophy in adults with chronic renal failure (CRF) might be mediated in part by alterations in circulating levels of the insulin-like growth factor (IGF) system components, we compared serum levels of IGF-I, IGF-II, IGF-binding protein (IGFBP)-3, IGFBP-4 and IGFBP-5 in adults with CRF (CRF patients with parathyroid hormone (PTH) < 100 pg/ml, PTH > 300 pg/ml and end-stage renal failure (ESRF) patients) versus age-matched controls. To evaluate the biological significance of alterations in circulating level of IGF system components, we compared the mitogenic activity of the sera on proliferation of normal human osteoblasts in vitro by using [³H]thymidine incorporation. We found severalfold increased serum levels of IGFBP-3 (2-fold), IGFBP-4 (5-fold) and slightly increased IGF-II levels in ESRF patients as well as a 2.6-fold increase in free IGF-I in CRF patients with PTH < 100 pg/ml. The mitogenic activity was found to be increased in serum of kidney failure patients compared to controls. This was most pronounced in CRF patients with PTH < 100 pg/ml showing also a significant increase in free IGF-I and the lowest levels of the IGF-inhibitory IGFBP-4. Our data support the hypothesis that alterations in serum levels of stimulating (i.e. free IGF-I) and inhibitory IGF system components (i.e. IGFBP-4) may influence osteoblastic cell proliferation in renal osteodystrophy.

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Severely Reduced Production of Klotho in Human Chronic Renal Failure Kidney

Koh

Fujimori

Nishiguchi

et al. 2001

Biochemical and Biophysical Research Communications

435

285

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Renal Osteodystrophy: New Insights in Pathophysiology and Treatment Modalities with Special Emphasis on the Insulin-Like Growth Factor System

Cited by 19 publications

References 167 publications

Changes in Bone Mineral Density, Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 in Kidney Transplant Recipients

Changes in Bone Mineral Density, Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 in Kidney Transplant Recipients

Evaluation of IGF System Component Levels and Mitogenic Activity of Uremic Serum on Normal Human Osteoblasts

Severely Reduced Production of Klotho in Human Chronic Renal Failure Kidney

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