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

Abstract

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.