Evaluation of IGF system component levels and mitogenic activity of uremicserum on normal human osteoblasts

To test the hypothesis that impairment in bone formation in renal osteodyst rophy 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 wi th parathyroid hormone (PTH) < 100 pg/ml, PTH > 300 pg/ml and end-stage ren al failure (ESRF) patients) versus age-matched controls. To evaluate the bi ological significance of alterations in circulating level of IGF system com ponents, we compared the mitogenic activity of the sera on proliferation of normal human osteoblasts in vitro by using [H-3]thymidine incorporation. W e 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 mit ogenic activity was found to be increased in serum of kidney failure patien ts 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 lowes t levels of the IGF-inhibitory IGFBP-4. Our data support the hypothesis tha t alterations in serum levels of stimulating (i.e. free IGF-I) and inhibito ry IGF system components (i.e. IGFBP-4) may influence osteoblastic cell pro liferation in renal osteodystrophy. Copyright (C) 2000 S. Karger AG, Basel.