Effects of short-term insulin-like growth factor-I (IGF-I) or growth hormone (GH) treatment on bone metabolism and on production of 1,25-dihydroxycholecalciferol in GH-deficient adults.

UNLABELLED Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 +/- 14 yr of age) were treated with IGF-I (5 micrograms/kg/h in a continuous s.c. infusion) and GH (0.03 IU/kg/daily s.c. injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2-3 days of both treatments (P < 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. CONCLUSIONS Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1 alpha-hydroxylase activity in vivo.

[1]  T. Kaku,et al.  Long‐Term Treatment of Indomethacin Reduces Vertebral Bone Mass and Strength in Ovariectomized Rats , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  S. Boonen,et al.  Age-Associated Decline in Human Femoral Neck Cortical and Trabecular Content of Insulin-Like Growth Factor I: Potential Implications for Age-Related (Type II) Osteoporotic Fracture Occurrence , 1997, Calcified Tissue International.

[3]  B. Hollis,et al.  Increased Serum 1,25-Dihydroxyvitamin D after Growth Hormone Administration is not Parathyroid Hormone-Mediated , 1997, Calcified Tissue International.

[4]  P. Lips,et al.  The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men. , 1997, The Journal of clinical endocrinology and metabolism.

[5]  J. Adams,et al.  Elderly patients with adult-onset growth hormone deficiency are not osteopenic. , 1997, The Journal of clinical endocrinology and metabolism.

[6]  E. Froesch,et al.  Effects of growth hormone (GH) and insulin-like growth factor-I on serum leptin in GH-deficient adults. , 1997, Diabetologia.

[7]  R. Bouillon,et al.  Effects of short‐term insulin‐like growth factor‐I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D3 production in healthy man , 1997, Journal of internal medicine.

[8]  P. Lips,et al.  The effect of growth hormone on histomorphometric indices of bone structure and bone turnover in growth hormone deficient men , 1997 .

[9]  A. Klibanski,et al.  Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. , 1996, The Journal of clinical endocrinology and metabolism.

[10]  S. Feld,et al.  Growth hormone, the insulin-like growth factor system, and the kidney. , 1996, Endocrine reviews.

[11]  C. Stewart,et al.  Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. , 1996, Physiological reviews.

[12]  P. Backeljauw,et al.  Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome--a clinical research center study. GHIS Collaborative Group. , 1996, The Journal of clinical endocrinology and metabolism.

[13]  P. Lips,et al.  Histomorphometric analysis of bone mass and bone metabolism in growth hormone deficient adult men. , 1996, Bone.

[14]  N. Mauras,et al.  Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans. , 1996, The Journal of clinical endocrinology and metabolism.

[15]  R. Margolis,et al.  Invited review of a workshop: anabolic hormones in bone: basic research and therapeutic potential. , 1996, The Journal of clinical endocrinology and metabolism.

[16]  S. Ljunghall,et al.  Effects of growth hormone and insulin-like growth factor I in men with idiopathic osteoporosis. , 1996, The Journal of clinical endocrinology and metabolism.

[17]  R. Marcus,et al.  Effects of recombinant insulin‐like growth factor‐I and growth hormone on bone turnover in elderly women , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  J. Guevara-Aguirre,et al.  A randomized, double blind, placebo-controlled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone receptor deficiency. , 1995, The Journal of clinical endocrinology and metabolism.

[19]  D. Johnston,et al.  The effects of prolonged growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults * , 1995, Clinical endocrinology.

[20]  J. Reynolds,et al.  Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. , 1995, Endocrinology.

[21]  R. Quarto,et al.  In vivo and in vitro effects of insulin-like growth factor-I (IGF-I) on femoral mRNA expression in old rats. , 1994, Bone.

[22]  F. Vrtovsnik,et al.  Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells. , 1994, The Journal of clinical investigation.

[23]  S. Mohan,et al.  Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging. , 1994, The Journal of clinical endocrinology and metabolism.

[24]  M. Preece,et al.  Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome). , 1993, The Journal of clinical endocrinology and metabolism.

[25]  W. O'Fallon,et al.  Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women. , 1993, The Journal of clinical endocrinology and metabolism.

[26]  J. Kaufman,et al.  Short and long‐term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone‐deficient males * , 1993, Clinical endocrinology.

[27]  L. Lönn,et al.  Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. , 1993, The Journal of clinical endocrinology and metabolism.

[28]  R. Bouillon,et al.  Influence of vitamin D on parathyroid function in the elderly. , 1992, The Journal of clinical endocrinology and metabolism.

[29]  S. Lamberts,et al.  The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition , 1992, Clinical endocrinology.

[30]  S. Ljunghall,et al.  Insulin-like growth factor I stimulates bone turnover in osteoporosis , 1992, The Lancet.

[31]  Z. Laron,et al.  Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism , 1992, The Lancet.

[32]  J. Kaufman,et al.  Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. , 1992, The Journal of clinical endocrinology and metabolism.

[33]  C. Hassager,et al.  The effect of growth hormone (GH) therapy on urinary pyridinoline cross‐links in GH‐deficient adults , 1991, Clinical endocrinology.

[34]  A. Parfitt.  Growth hormone and adult bone remodelling , 1991, Clinical endocrinology.

[35]  T. Martin,et al.  Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. , 1991, Endocrinology.

[36]  L. Mosekilde,et al.  A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers , 1990, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  C. Christiansen,et al.  Effects of growth hormone (GH) on plasma bone Gla protein in GH-deficient adults. , 1990, The Journal of clinical endocrinology and metabolism.

[38]  J. Eisman,et al.  Somatomedin-C, physical fitness, and bone density. , 1990, The Journal of clinical endocrinology and metabolism.

[39]  R. Marcus,et al.  Effects of short term administration of recombinant human growth hormone to elderly people. , 1990, The Journal of clinical endocrinology and metabolism.

[40]  D. Rowe,et al.  Insulin-like growth factor I regulates type I procollagen messenger ribonucleic acid steady state levels in bone of rats. , 1989, Endocrinology.

[41]  E. Froesch,et al.  Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[42]  E. Froesch,et al.  Recombinant human insulin-like growth factor I stimulates growth and has distinct effects on organ size in hypophysectomized rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[43]  E. Froesch,et al.  Growth hormone dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor I. , 1988, Biochemical and biophysical research communications.

[44]  E. Canalis,et al.  Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. , 1988, Endocrinology.

[45]  R L Hintz,et al.  Insulin-like growth factors I and II: aging and bone density in women. , 1984, The Journal of clinical endocrinology and metabolism.

[46]  D. Clemmons.  Multiple hormones stimulate the production of somatomedin by cultured human fibroblasts. , 1984, The Journal of clinical endocrinology and metabolism.

[47]  D. Clemmons,et al.  6 Factors controlling blood concentration of somatomedin C , 1984 .

[48]  D. Clemmons,et al.  Factors controlling blood concentration of somatomedin C. , 1984, Clinics in endocrinology and metabolism.

[49]  R. Tsang,et al.  Effects of growth hormone replacement therapy on 1,25-dihydroxyvitamin D and calcium metabolism. , 1983, The Journal of clinical endocrinology and metabolism.

[50]  E. Canalis,et al.  Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. , 1980, The Journal of clinical investigation.

[51]  J. Zerwekh,et al.  Effect of Growth Hormone Administration: Reciprocal Changes in Serum lα,25-Dihydroxyvitamin D and Intestinal Calcium Absorption* , 1980 .