title: Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency.
abstract: 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 one female aged 21-43 years, mean age 28 years) participated in the study. 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 period, the study population received increasing doses of GH at 4-week intervals (1, 2 and 4 U/m2). Blood samples were collected in the fasting state at 7.00 h on the last day of each period and assayed for serum levels of osteocalcin (S-BGP), bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S-PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (S-ICTP) and N-terminal propeptide of type III collagen (S-PIIINP). Following replacement therapy, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 increased sequentially with time (p < 0.001 and p < 0.001, MANOVA) and the values were elevated significantly over baseline levels after treatment with 1 U/m2. Serum BGP values were below normal at the start of the study and increased gradually following GH treatment to levels in the low-normal range. Baseline values for serum bone alkaline phosphatase (B-ALP), PICP and PIIINP were within the normal range. The collagen parameters increased with GH replacement (p < 0.001, MANOVA) to levels above normal, whereas B-ALP stayed within normal limits. Serum ICTP values were elevated above the normal range at baseline, indicating increased bone resorption in GHD. A linear increase in values was observed with GH treatment (p < 0.001, MANOVA). Serum ICTP did not correlate significantly with the bone formative parameters 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.
authors.affiliation: Department of Medical Endocrinology, National University Hospital, Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Bollerslev
authors.forename: J
authors.initials: J
authors.lastname: Møller
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: O
authors.initials: O
authors.lastname: Djøseland
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000172:deficiency* / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D011347:Procollagen / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011994:Recombinant Proteins; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D000469:Alkaline Phosphatase