Different responses of bone alkaline phosphatase isoforms during recombinant insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults with growth hormone deficiency.
We studied serum bone alkaline phosphatase (ALP) isoforms and other markers of bone turnover in growth hormone-deficient (GHD) adults (n = 22). The patients were followed during 1 week of insulin-like growth factor-I (IGF-I) administration, 40 micrograms/kg of body weight/day (n = 6), and during 24 months of growth hormone (GH) therapy, 0.125 IU/kg of body weight/week for the first month, and then 0.250 IU/kg of body weight/week (n = 20). Six ALP isoforms were separated and quantified by high-performance liquid chromatography: one bone/intestinal, two bone (B1, B22), and three liver ALP isoforms. At baseline, the mean levels of B1, B22, and osteocalcin were higher in GHD adults than in healthy adults. After 2 week of IGF-I administration and 1 month of GH therapy, only B1 was decreased. We suggest that the initial decrease of B1 during GH therapy could be an effect of endocrine IGF-I action mediated by GH. After 3 months of GH therapy, both B1 and B2 increased as compared with placebo. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary pyridinoline cross-links/creatinine ratio increased during GH therapy. PICP increased significantly before bone ALP and osteocalcin, indicating early stimulation of type I collagen synthesis as previously demonstrated by in vitro models. Different responses of the bone ALP isoforms during IGF-I and during GH therapy suggest different regulations in vivo.
Magnusson
P
P
Department of Clinical Chemistry, Linköping University Hospital, Sweden.
Degerblad
M
M
Sääf
M
M
Larsson
L
L
Thorén
M
M
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood* / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology*; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007527:Isoenzymes / Q000097:blood* / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D007527:Isoenzymes; D010446:Peptide Fragments; D011347:Procollagen; D011994:Recombinant Proteins; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase