The IGF/IGFBP system in relation to macroscopic bone architecture in pediatric renal transplant patients

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.

Bone Density and Cortical Structure after Pediatric Renal Transplantation

“…Decreased physical activity and potential alterations in the insulin-like growth factor system may also have contributed to persistent cortical structural deficits. 28 In a related study, we also observed that greater gains in muscle were significantly associated with lesser declines in section modulus after diagnosis and treatment with glucocorticoids in children with Crohn disease. 19 We recently examined pQCT trabecular BMD in children with CKD (including 86 with eGFR ,30 ml/min per 1.73 m 2 ) and no history of renal transplantation, anticipating that trabecular BMD Z-scores would be elevated because of an anabolic effect of PTH.…”

Metabolic bone disease after renal transplantation

“…Finally, the overall decreased physical activity in KTx patients may be another important contributing factor [36]. Finally, the overall decreased physical activity in KTx patients may be another important contributing factor [36].…”