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 othe r conditions, growth retardation, hyperparathyroidism and uremic osteo dystrophy. Many children with CRF are now being treated with growth ho rmone (GH). Since GH has a direct mitogenic effect on osteoblasts in c ulture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phophatase (AP), bone GLA-protein (BGP) and bo ne mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) a nd 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. Dur ing GH therapy, a similar increase in height velocity and IGF-I were n oted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) v s. 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 1.5 +/- 5.6 nmol/l (p < 0.0 1), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (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 mug/l. 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 paramete rs tested. BMD in the SS group increased significantly during treatmen t 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 i n 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). Th ere were no changes in calcium, inorganic phosphorus, 1,25-dihydroxyvi tamin D3 or intact PTH throughout the study in either group. Serum pho sphorus and intact PTH were significantly higher in the CRF than in th e SS group both before and at the end of the 1 st year of GH treatment . We conclude that, during the 1st year of GH treatment, growth veloci ty and IGF-I increase in both groups of patients. The increment in ost eoblastic activity was greater in children without CRF.