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Endocrine Reviews 19 (1): 55-79
Copyright © 1998 by The Endocrine Society

Growth Hormone and Bone1

Claes Ohlsson, Bengt-Åke Bengtsson, Olle G. P. Isaksson, Troels T. Andreassen and Maria C. Slootweg

Research Centre for Endocrinology and Metabolism (C.O., B-Å.B., O.I., M.S.), Sahlgrenska University Hospital, S-41345 Göteborg, Sweden; Diabetes Branch (C.O.), The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Department of Connective Tissue Biology (T.T.A.), Institute of Anatomy, University of Aarhus, Aarhus, Denmark; and Eli Lilly, Netherlands (M.S.), Nieuwegein, Netherlands

I. Introduction
II. Effects of GH on Longitudinal Bone Growth
A. GH and regulation of postnatal longitudinal bone growth
B. Results supporting an important physiological role of IGF-I for bone growth
C. Evaluation of the somatomedin theory vs. the dual effector theory
III. Effect of GH in Vitro
A. Effects of GH in bone tissue cultures
B. Effects of GH on osteoblasts
C. Effects of GH on osteoclasts
IV. Effects of GH on Bone Metabolism in Animals
A. Effects of GH deficiency and GH replacement on bone parameters
B. Effects of GH treatment on bone parameters of animals with normal GH secretion
C. Effects of GH on fracture healing
V. Effects of GH on Bone Metabolism in Humans
A. Bone metabolism in patients with acromegaly and GH deficiency
B. Effects of the GH/IGF-I axis on bone metabolism and bone mass in patients with normal GH secretion
VI. Summary and Conclusions




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 JNCI J Natl Cancer InstHome page
M. S. Sandhu, D. B. Dunger, and E. L. Giovannucci
Insulin, Insulin-Like Growth Factor-I (IGF-I), IGF Binding Proteins, Their Biologic Interactions, and Colorectal Cancer
J Natl Cancer Inst, July 3, 2002; 94(13): 972 - 980.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. D. Wallace, W. J. Abbott-Johnson, D. H. G. Crawford, R. Barnard, J. M. Potter, and R. C. Cuneo
GH Treatment in Adults with Chronic Liver Disease: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study
J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2751 - 2759.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
C. J. Greenhalgh, P. Bertolino, S. L. Asa, D. Metcalf, J. E. Corbin, T. E. Adams, H. W. Davey, N. A. Nicola, D. J. Hilton, and W. S. Alexander
Growth Enhancement in Suppressor of Cytokine Signaling 2 (SOCS-2)-Deficient Mice Is Dependent on Signal Transducer and Activator of Transcription 5b (STAT5b)
Mol. Endocrinol., June 1, 2002; 16(6): 1394 - 1406.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
D. Zivadinovic, M. Tomic, D. Yuan, and S. S. Stojilkovic
Cell-Type Specific Messenger Functions of Extracellular Calcium in the Anterior Pituitary
Endocrinology, February 1, 2002; 143(2): 445 - 455.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
C. Christmas, K. G. O'Connor, S. M. Harman, J. D. Tobin, T. Munzer, M. F. Bellantoni, C. St. Clair, K. M. Pabst, J. D. Sorkin, and M. R. Blackman
Growth Hormone and Sex Steroid Effects on Bone Metabolism and Bone Mineral Density in Healthy Aged Women and Men
J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2002; 57(1): M12 - 18.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
J. Nakae, Y. Kido, and D. Accili
Distinct and Overlapping Functions of Insulin and IGF-I Receptors
Endocr. Rev., December 1, 2001; 22(6): 818 - 835.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
C. Salto, J. M. Kindblom, C. Johansson, Z. Wang, H. Gullberg, K. Nordstrom, A. Mansen, C. Ohlsson, P. Thoren, D. Forrest, et al.
Ablation of TR{alpha}2 and a Concomitant Overexpression of {alpha}1 Yields a Mixed Hypo- and Hyperthyroid Phenotype in Mice
Mol. Endocrinol., December 1, 2001; 15(12): 2115 - 2128.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
G. Gotherstrom, J. Svensson, J. Koranyi, M. Alpsten, I. Bosaus, B.-A. Bengtsson, and G. Johannsson
A Prospective Study of 5 Years of GH Replacement Therapy in GH-Deficient Adults: Sustained Effects on Body Composition, Bone Mass, and Metabolic Indices
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4657 - 4665.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. M. Fitts, R. M. Klein, and C. A. Powers
Estrogen and Tamoxifen Interplay with T3 in Male Rats: Pharmacologically Distinct Classes of Estrogen Responses Affecting Growth, Bone, and Lipid Metabolism, and Their Relation to Serum GH and IGF-I
Endocrinology, October 1, 2001; 142(10): 4223 - 4235.
[Abstract] [Full Text] [PDF]

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 Mol. Pathol.Home page
Z Laron
Insulin-like growth factor 1 (IGF-1): a growth hormone
Mol. Pathol., October 1, 2001; 54(5): 311 - 316.
[Abstract] [Full Text] [PDF]

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 JDRHome page
V. Visnapuu, T. Peltomaki, O. Ronning, T. Vahlberg, and H. Helenius
Growth Hormone and Insulin-like Growth Factor I Receptors in the Temporomandibular Joint of the Rat
Journal of Dental Research, October 1, 2001; 80(10): 1903 - 1907.
[Abstract] [PDF]

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 EndocrinologyHome page
A. Flores-Morales, N. Stahlberg, P. Tollet-Egnell, J. Lundeberg, R. L. Malek, J. Quackenbush, N. H. Lee, and G. Norstedt
Microarray Analysis of the in Vivo Effects of Hypophysectomy and Growth Hormone Treatment on Gene Expression in the Rat
Endocrinology, July 1, 2001; 142(7): 3163 - 3176.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
N. Miyakoshi, X. Qin, Y. Kasukawa, C. Richman, A. K. Srivastava, D. J. Baylink, and S. Mohan
Systemic Administration of Insulin-Like Growth Factor (IGF)-Binding Protein-4 (IGFBP-4) Increases Bone Formation Parameters in Mice by Increasing IGF Bioavailability via an IGFBP-4 Protease-Dependent Mechanism
Endocrinology, June 1, 2001; 142(6): 2641 - 2648.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
J. A. Gusenoff, S. M. Harman, J. D. Veldhuis, J. J. Jayme, C. St. Clair, T. Munzer, C. Christmas, K. G. O'Connor, T. E. Stevens, M. F. Bellantoni, et al.
Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men
Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E616 - E625.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
D. Le Roith, C. Bondy, S. Yakar, J.-L. Liu, and A. Butler
The Somatomedin Hypothesis: 2001
Endocr. Rev., February 1, 2001; 22(1): 53 - 74.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
O. Vidal, M. K. Lindberg, K. Hollberg, D. J. Baylink, G. Andersson, D. B. Lubahn, S. Mohan, J.-A. Gustafsson, and C. Ohlsson
Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice
PNAS, May 9, 2000; 97(10): 5474 - 5479.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
R. S. MacDonald
The Role of Zinc in Growth and Cell Proliferation
J. Nutr., May 1, 2000; 130(5): 1500S - 1508.
[Abstract] [Full Text]

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 JCOHome page
J. Pfeilschifter and I. J. Diel
Osteoporosis Due to Cancer Treatment: Pathogenesis and Management
J. Clin. Oncol., April 7, 2000; 18(7): 1570 - 1593.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Longobardi, N. Keay, C. Ehrnborg, A. Cittadini, T. Rosén, R. Dall, M. A. Boroujerdi, E. E. Bassett, M. L. Healy, C. Pentecost, et al.
Growth Hormone (GH) Effects on Bone and Collagen Turnover in Healthy Adults and Its Potential as a Marker of GH Abuse in Sports: A Double Blind, Placebo-Controlled Study
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1505 - 1512.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
N. Mauras, K. O. O’Brien, S. Welch, A. Rini, K. Helgeson, N. E. Vieira, and A. L. Yergey
Insulin-Like Growth Factor I and Growth Hormone (GH) Treatment in GH-Deficient Humans: Differential Effects on Protein, Glucose, Lipid, and Calcium Metabolism
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1686 - 1694.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
B. M. K. Biller, G. Sesmilo, H. B. A. Baum, D. Hayden, D. Schoenfeld, and A. Klibanski
Withdrawal of Long-Term Physiological Growth Hormone (GH) Administration: Differential Effects on Bone Density and Body Composition in Men with Adult-Onset GH Deficiency
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 970 - 976.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
L. Rui, S. F. Archer, L. S. Argetsinger, and C. Carter-Su
Platelet-derived Growth Factor and Lysophosphatidic Acid Inhibit Growth Hormone Binding and Signaling via a Protein Kinase C-dependent Pathway
J. Biol. Chem., January 28, 2000; 275(4): 2885 - 2892.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. D. Wallace, R. C. Cuneo, P. A. Lundberg, T. Rosén, J. O. L. Jørgensen, S. Longobardi, N. Keay, L. Sacca, J. S. Christiansen, B.-A. Bengtsson, et al.
Responses of Markers of Bone and Collagen Turnover to Exercise, Growth Hormone (GH) Administration, and GH Withdrawal in Trained Adult Males
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 124 - 133.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
J. Van Wyk
Insulin-Like Growth Factors and Skeletal Growth: Possibilities for Therapeutic Interventions
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4349 - 4354.
[Full Text]

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 EndocrinologyHome page
N. R. Cox, N. E. Morrison, J. L. Sartin, F. C. Buonomo, B. Steele, and H. J. Baker
Alterations in the Growth Hormone/Insulin-Like Growth Factor I Pathways in Feline GM1 Gangliosidosis
Endocrinology, December 1, 1999; 140(12): 5698 - 5704.
[Abstract] [Full Text]

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 EndocrinologyHome page
N. Miyakoshi, C. Richman, X. Qin, D. J. Baylink, and S. Mohan
Effects of Recombinant Insulin-Like Growth Factor-Binding Protein-4 on Bone Formation Parameters in Mice
Endocrinology, December 1, 1999; 140(12): 5719 - 5728.
[Abstract] [Full Text]

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 FASEB J.Home page
J. WANG, J. ZHOU, and C. A. BONDY
Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy
FASEB J, November 1, 1999; 13(14): 1985 - 1990.
[Abstract] [Full Text]

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 Arch. Dis. Child.Home page
H. Robson
Bone growth mechanisms and the effects of cytotoxic drugs
Arch. Dis. Child., October 1, 1999; 81(4): 360 - 364.
[Full Text]

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 J. Clin. Endocrinol. Metab.Home page
S. Mora, P. Pitukcheewanont, J. C. Nelson, and V. Gilsanz
Serum Levels of Insulin-Like Growth Factor I and the Density, Volume, and Cross-Sectional Area of Cortical Bone in Children
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2780 - 2783.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
K. Sjogren, J.-L. Liu, K. Blad, S. Skrtic, O. Vidal, V. Wallenius, D. LeRoith, J. Tornell, O. G. P. Isaksson, J.-O. Jansson, et al.
Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice
PNAS, June 8, 1999; 96(12): 7088 - 7092.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
S. Göthe, Z. Wang, L. Ng, J. M. Kindblom, A. C. Barros, C. Ohlsson, B. Vennström, and D. Forrest
Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation
Genes & Dev., May 15, 1999; 13(10): 1329 - 1341.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
G. Van den Berghe, P. Wouters, F. Weekers, S. Mohan, R. C. Baxter, J. D. Veldhuis, C. Y. Bowers, and R. Bouillon
Reactivation of Pituitary Hormone Release and Metabolic Improvement by Infusion of Growth Hormone-Releasing Peptide and Thyrotropin-Releasing Hormone in Patients with Protracted Critical Illness
J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1311 - 1323.
[Abstract] [Full Text]

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 EndocrinologyHome page
G. Maor, Y. Segev, and M. Phillip
Testosterone Stimulates Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I-Receptor Gene Expression in the Mandibular Condyle--A Model of Endochondral Ossification
Endocrinology, April 1, 1999; 140(4): 1901 - 1910.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
M. Russell-Aulet, B. Shapiro, C. A. Jaffe, M. D. Gross, and A. L. Barkan
Peak Bone Mass in Young Healthy Men Is Correlated with the Magnitude of Endogenous Growth Hormone Secretion
J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3463 - 3468.
[Abstract] [Full Text]


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