Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure

Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phophatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 ± 0.77 to 8.38 ± 1.25 (p < 0.001) vs. 4.0 ± 0.6 to 7.14 ± 1.3 cm/year (p < 0.001) and 7.8 ± 2.6 to 21.8 ± 7.5 (p < 0.01) vs. 7.9 ± 1.3 to 21.5 ± 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 ± 27 to 274 ± 50 IU/1 (p < 0.01) in the SS group but not in CRF patients (223 ± 58 pre- 218 ± 51 IU/I post-GH therapy). BGP increased significantly in both groups (p ‹ 0.01) from 15 ± 2.1 to 22 ± 3.5 and from 49 ± 11 to 71 ± 36 μg/1. BGP was significantly higher in the CRF group, both before initiation of the study and after 1 year of GH therapy. No correlation was found between BGP and serum AP or any of the other blood parameters tested. BMD in the SS group increased significantly during treatment from 0.63 ± 0.11 to 0.75 ± 0.11 g/cm² (p < 0.05). This increase was not different from that which could be expected for the respective ages as we have previously reported. In the CRF group, the increase in BMD was not significant. The respective changes in BMD in the SS and CRF groups were 0.04 ± 0.02 and 0.10 ± 0.07 g/cm² (p = 0.043). There were no changes in calcium, inorganic phosphorus, 1,25-dihy- droxyvitamin D₃ or intact PTH throughout the study in either group. Serum phosphorus and intact PTH were significantly higher in the CRF than in the SS group both before and at the end of the 1st year of GH treatment. We conclude that, during the 1 st year of GH treatment, growth velocity and IGF-I increase in both groups of patients. The increment in osteoblastic activity was greater in children without CRF.