DOSE-DEPENDENT EFFECTS OF RECOMBINANT HUMAN GROWTH-HORMONE ON BIOCHEMICAL MARKERS OF BONE AND COLLAGEN-METABOLISM IN ADULT GROWTH-HORMONE DEFICIENCY

Administration of growth hormone (GH) to patients with growth hormone deficiency (GHD) has beneficial effects, but so far has been employed only empirically. We have, therefore, investigated the dose-dependent effect of GH on target tissue by studying biochemical markers of bone and collagen turnover in GHD. Then patients with GHD (nine males and o ne female aged 21-43 years, mean age 28 years) participated in the stu dy. Growth hormone deficiency was defined as a peak serum GH response of less than 15 mU/l in two provocation tests. After a 4-week run-in p eriod, the study population received increasing doses of GH at 4-week intervals (1, 2 and 4 U/m(2)). Blood samples were collected in the fas ting state at 7.00 h on the last day of each period and assayed for se rum levels of osteocalcin (S-BGP), bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S-PICP), carboxy-terminal py ridinoline cross-linked telopeptide of type I collagen (S-ICTP) and N- terminal propeptide of type III collagen (S-PIIINP). Following replace ment therapy, serum insulin-like growth factor I and insulin-like grow th factor binding protein 3 increased sequentially with time (p<0.001 and p<0.001, MANOVA) and the values were elevated significantly over b aseline levels after treatment with 1 U/m(2). Serum BGP values were be low normal at the start of the study and increased gradually following GH treatment to levers in the low-normal range. Baseline values for s erum bone alkaline phosphatase (B-ALP), PICP and PIIINP were within th e normal range. The collagen parameters increased with GH replacement (p < 0.001, MANOVA) to levels above normal, whereas B-ALP stayed withi n normal limits. Serum ICTP values were elevated above the normal rang e at baseline, indicating increased bone resorption in GHD. A linear i ncrease in values was observed with GH treatment (p < 0.001, MANOVA). Serum ICTP did not correlate significantly with the bone formative par ameters but was correlated positively to PIIINP. The sensitivity of S- ICTP as a bone resorptive marker is thus questioned. In conclusion, a dose-dependent increase in markers of growth hormone metabolism and in biochemical markers of both bone and non-bone collagen synthesis was seen following incremental doses of GH in GHD.