J. Bollerslev et al., DOSE-DEPENDENT EFFECTS OF RECOMBINANT HUMAN GROWTH-HORMONE ON BIOCHEMICAL MARKERS OF BONE AND COLLAGEN-METABOLISM IN ADULT GROWTH-HORMONE DEFICIENCY, European journal of endocrinology, 135(6), 1996, pp. 666-671
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.