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The IGF/IGFBP system in relation to macroscopic bone architecture in pediatric renal transplant patients
Daniela Kiepe1, Eva-Maria Rüth, Werner F Blum
1University Children's Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany. daniela.kiepe@med.uni-heidelberg.de
Insights
Pediatric kidney transplant patients show thin bones due to functional insulin-like growth factor (IGF) deficiency. Elevated inhibitory IGF binding proteins (IGFBPs) contribute to this bone disease, impacting periosteal growth.
Area of Science:
- Pediatric Endocrinology
- Nephrology
- Bone Biology
Background:
- Pediatric renal transplant recipients often develop post-transplant bone disease, characterized by reduced peripheral bone cortical thickness.
- The insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system is a key regulator of periosteal bone growth.
Purpose of the Study:
- To investigate the hypothesis that functional insulin-like growth factor (IGF) deficiency contributes to reduced cortical thickness in pediatric renal transplant recipients.
- To analyze the relationship between serum IGF/IGFBP system components and bone architecture in these patients.
Main Methods:
- Cross-sectional study of 55 pediatric renal transplant recipients.
- Peripheral quantitative computed tomography (pQCT) to assess bone architecture and muscle size.
- Specific radioimmunoassays to measure serum IGF and IGFBP levels.
Main Results:
- Serum IGF-I levels were normal, but IGF-II levels were elevated. IGFBP-3, -4, and -6 levels were significantly increased, indicating functional IGF deficiency.
- Cortical thickness at both proximal and distal forearm positively correlated with serum IGF-I levels.
- Elevated inhibitory IGFBPs suggest a role in impaired bone modeling.
Conclusions:
- The IGF/IGFBP system in pediatric renal transplant recipients is dysregulated, with increased inhibitory IGFBPs leading to functional IGF deficiency.
- This hormonal imbalance is associated with reduced bone cortical thickness, highlighting the system's importance in periosteal bone development.
Abstract:
The post-transplant bone disease of the peripheral skeleton in pediatric renal transplant recipients is characterized by an inadequately thin bone cortex in relation to muscular force. A major hormonal modulator of periosteal growth is the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system. We therefore hypothesized that the reduced cortical thickness in these patients may be due to functional IGF deficiency. To test this hypothesis, we investigated 55 patients (mean estimated glomerular filtration rate 86.3 +/- 30.0 ml/min/1.73 m(2)) in a cross-sectional study. Parameters of macroscopic bone architecture and forearm muscle size were analyzed by peripheral quantitative computed tomography (pQCT), and serum IGF/IGFBP system components were measured by specific radioimmunoassays. The mean (+/- standard deviation) standardized serum IGF-I (0.20 +/- 1.16 score) level was normal, while the mean IGF-II (1.16 +/- 0.11 score) level was significantly elevated. Serum IGFBP-1 and IGFBP-2 levels were not altered, whereas the IGFBP-3 (1.34 +/- 0.15 score) level was significantly increased. The serum IGFBP-4 level was slightly elevated (by 11%), the IGFBP-6 level was markedly (2.3-fold) elevated, while the IGFBP-5 level was comparable to that of the control. The respective age-adjusted cortical thickness at both the proximal (r = 0.407, P < 0.005) and distal (r = 0.383, P < 0.01) forearm was positively correlated with the standardized serum IGF-I level. In conclusion, the serum IGF/IGFBP system in pediatric renal transplant recipients is characterized by an increase in the levels of the inhibitory IGFBPs, IGFBP-3, -4 and -6, resulting in a functional IGF deficiency. The positive correlation of IGF-I with cortical thickness underlines the importance of this hormonal system in the modeling of bone, particularly periosteal growth.
