Growth Hormone pp 237-252 | Cite as

Effects of GH on Bone Metabolism and Bone Mass

  • Claes Ohlsson
Chapter
Part of the Endocrine Updates book series (ENDO, volume 4)

Abstract

It is well known that growth hormone (GH) is important in the regulation of longitudinal bone growth (1; 2). Its role in the regulation of bone metabolism in man has not been understood until recently (1). Bone remodeling is regulated by a balance between bone resorption and bone formation. Recent studies, which demonstrate that GH exerts potent effects on bone remodeling, will be discussed in this chapter. Finally a hypothetical model for the mechanism of action of GH in the regulation of bone remodeling and bone mass will be presented.

Keywords

Bone Mineral Density Growth Hormone Bone Mass Growth Hormone Deficiency Growth Hormone Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ohlsson C., Bengtsson B., Isaksson O., Andreassen T. and Slootweg M. Growth hormone and bone. Endocr Rev 1998, in press.Google Scholar
  2. 2.
    Ohlsson C, Lindahl A, Isgaard J. and Isaksson O. The dual effector theory. In Handbook of Physiology. Kostyo J (Ed) 1997.Google Scholar
  3. 3.
    Nilsson A., Swolin D., Enerback S. and Ohlsson C. Expression of functional growth hormone receptors in cultured human osteoblast-like cells. J Clin Endocrinol Metab 1995, 80:3483–3488.PubMedCrossRefGoogle Scholar
  4. 4.
    Barnard R., Ng K.W., Martin T.J. and Waters M.J. Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. Endocrinology 1991, 128:1459–1464.PubMedCrossRefGoogle Scholar
  5. 5.
    Salles J.P., De Vries C.P, Netelenbos J.C. and Slootweg M.C. Dexamethasone increases and serum decreases growth hormone receptor binding to UMR-106.01 rat osteosarcoma cells. Endocrinology 1994, 134:1455–1459.PubMedCrossRefGoogle Scholar
  6. 6.
    Slootweg M.C., Ohlsson C., Salles J.P., de Vries C.P. and Netelenbos J.C. Insulin-like growth factor binding proteins-2 and-3 stimulate growth hormone receptor binding and mitogenesis in rat osteosarcoma cells. Endocrinology 1995, 136:4210–4217.PubMedCrossRefGoogle Scholar
  7. 7.
    Slootweg M., Ohlsson C., van Elk E., Netelenbos J. and Andress D. Growth hormone receptor activity is stimulated by insulin-like growth factor binding protein 5 in rat osteosarcoma cells. Growth Regul 1996, 6:238–246.PubMedGoogle Scholar
  8. 8.
    Leung K., Rajkovic I.A., Peters E., Markus I., Van Wyk J.J. and Ho K.K. Insulin-like growth factor I and insulin down-regulate growth hormone (GH) receptors in rat osteoblasts: evidence for a peripheral feedback loop regulating GH action. Endocrinology 1996, 137:2694–2702.PubMedCrossRefGoogle Scholar
  9. 9.
    Slootweg M., Swolin D., Netelenbos J., Isaksson O. and Ohlsson C. Estrogen enhances growth hormone receptor expression and growth hormone action in rat osteosarcoma cells and human osteoblast-like cells. J Endocrinol 1997, 151:159–164.CrossRefGoogle Scholar
  10. 10.
    Kassem M., Blum W., Ristelli J., Mosekilde L. and Eriksen E.F. Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro. Calcif Tissue Int 1993, 52:222–226.PubMedCrossRefGoogle Scholar
  11. 11.
    Slootweg M.C., van Buul-Offers S.C., Herrmann-Erlee M.P., van der Meer J.M. and Duursma S.A. Growth hormone is mitogenic for fetal mouse osteoblasts but not for undifferentiated bone cells. J Endocrinol 1988, 116:R11–R13.PubMedCrossRefGoogle Scholar
  12. 12.
    Swolin D. and Ohlsson C. Growth hormone increases interleukin-6 produced by human osteoblast-like cells. J Clin Endocrinol Metab 1996, 81:4329–4333.PubMedCrossRefGoogle Scholar
  13. 13.
    Kassem M., Brixen K., Mosekilde L. and Eriksen E.F. Human marrow stromal osteoblast-like cells do not show reduced responsiveness to in vitro stimulation with growth hormone in patients with postmenopausal osteoporosis. Calcif Tissue Int 1994, 54:1–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Kassem M., Mosekilde L. and Eriksen E.F. Growth hormone stimulates proliferation of normal human bone marrow stromal Osteoblast precursor cells in vitro. Growth Regul 1994, 4:131–135.PubMedGoogle Scholar
  15. 15.
    Okazaki R, Conover C.A., Harris S.A., Spelsberg T.C. and Riggs B.L. Normal human osteoblast-like cells consistently express genes for insulinlike growth factors I and II but transformed human Osteoblast cell lines do not. Journal of Bone and Mineral Research 1995, 10:788–795.PubMedCrossRefGoogle Scholar
  16. 16.
    Swolin D., Brantsing C., Matejka G. and Ohlsson C. Cortisol decreases IGF-I mRNA levels in human osteoblast-like cells. J Endocrinol 1996, 149:397–403.PubMedCrossRefGoogle Scholar
  17. 17.
    Chenu C., Valentin-Opran A., Chavassieux P., Saez S., Meunier P.J. and Delmas P.D. Insulin like growth factor I hormonal regulation by growth hormone and by 1,25(OH)2D3 and activity on human osteoblast-like cells in short-term cultures. Bone 1990, 11:81–86.PubMedCrossRefGoogle Scholar
  18. 18.
    Morel G., Chavassieux P., Barenton B., Dubois P.M., Meunier P.J. and Boivin G. Evidence for a direct effect of growth hormone on osteoblasts. Cell Tissue Res 1993, 273:279–286.PubMedCrossRefGoogle Scholar
  19. 19.
    Kanzaki S., Baxter R.C., Knutsen R, Baylink D.J. and Mohan S. Evidence that human bone cells in culture secrete insulin-like growth factor (IGF)-II and IGF binding protein-3 but not acid-labile subunit both under basal and regulated conditions. Journal of Bone and Mineral Research 1995, 10:854–858.PubMedCrossRefGoogle Scholar
  20. 20.
    Hayden J.M., Mohan S. and Baylink DJ. The insulin-like growth factor system and the coupling of formation to resorption. Bone 1995, 17:93S–98S.PubMedCrossRefGoogle Scholar
  21. 21.
    Schmid C., Ernst M., Zapf J. and Froesch E.R. Release of insulin-like growth factor carrier proteins by osteoblasts: stimulation by estradiol and growth hormone. Biochem Biophys Res Commun 1989, 160:788–794.PubMedCrossRefGoogle Scholar
  22. 22.
    McCarthy T.L., Casinghino S., Centrella M. and Canalis E. Complex pattern of insulin-like growth factor binding protein expression in primary rat Osteoblast enriched cultures: regulation by Prostaglandin E2, growth hormone, and the insulin-like growth factors. J Cell Physiol 1994, 160:163–175.PubMedCrossRefGoogle Scholar
  23. 23.
    Mohan S., Strong D.D., Lempert U.G., Tremollieres F., Wergedal J.E. and Baylink DJ. Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells. Acta Endocrinol (Copenh) 1992, 127:555–564.Google Scholar
  24. 24.
    Chen T.L., Liu F., Bates R.L. and Hintz R.L. Further characterization of insulin-like-growth factor binding proteins in rat osteoblast-like cell cultures: modulation by 17 beta-estradiol and human growth hormone. Endocrinology 1991, 128:2489–2496.PubMedCrossRefGoogle Scholar
  25. 25.
    Lewinson D., Shenzer P. and Hochberg Z. Growth hormone involvement in the regulation of tartrate-resistant acid phosphatase-positive cells that are active in cartilage and bone résorption. Calcif Tissue Int 1993, 52:216–221.PubMedCrossRefGoogle Scholar
  26. 26.
    Nishiyama K., Sugimoto T., Kaji H., Kanatani M., Kobayashi T. and Chihara K. Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation. Endocrinology 1996, 137:35–41.PubMedCrossRefGoogle Scholar
  27. 27.
    Ransjo M., Lerner U. and Ohlsson C. Growth hormone inhibits formation of osteoclast-like cells in mouse bone marrow cultures. J Bone Miner Res 1996, 1l:suppl T394.Google Scholar
  28. 28.
    Schmidt I.U., Dobnig H. and Turner R.T. Intermittent parathyroid hormone treatment increases Osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats. Endocrinology 1995, 136:5127–5134.PubMedCrossRefGoogle Scholar
  29. 29.
    Andreassen T.T., Jorgensen RH., Flyvbjerg A., Orskov H. and Oxlund H. Growth hormone stimulates bone formation and strength of cortical bone in aged rats. Journal of Bone and Mineral Research 1995, 10:1057–1067.PubMedCrossRefGoogle Scholar
  30. 30.
    Nowak I, Nygaard H. and Eschen C. Growth hormone and/or estradiol and gestagen as a treatment of osteoporosis in the aged ovariectomized rat. J Bone Miner Res 1995, suppl 1:S252.Google Scholar
  31. 31.
    Andreassen T. and Oxlund H. Additive anabolic effects of growth hormone and parathyroid hormone on vertebral body cortical and cancellous bone in old ovariectomized rats. J Bone Miner Res 1996, suppl 1:S457.Google Scholar
  32. 32.
    Noland K., Orhii P., Rutstein J. and Kalu D. Effect of growth hormone therapy on cortical bone in aged ovariectomized rats. J Bone Miner Res 1996, suppl 1: S458.Google Scholar
  33. 33.
    Orhii P., Noland K., Rutstein J. and Kalu D. Effect of growth hormone therapy on cancellous bone in aged ovariectomized rats. J Bone Miner Res 1996, suppl 1:S458.Google Scholar
  34. 34.
    Verhaeghe J., van Bree R, Van Herck E., Thomas H., Skottner A., Dequeker J Mosekilde L., Einhorn T.A. and Bouillon R. Effects of recombinant human growth hormone and insulin-like growth factor-I, with or without 17 beta-estradiol, on bone and mineral homeostasis of aged ovariectomized rats. Journal of Bone and Mineral Research 1996, 11:1723–1735.PubMedCrossRefGoogle Scholar
  35. 35.
    Eschen C. and Andreassen T.T. Growth hormone normalizes vertebral strength in ovariectomized rats. Calcif Tissue Int 1995, 57:392–396.PubMedCrossRefGoogle Scholar
  36. 36.
    Wolf E., Rapp K. and Brem G. Expression of metallothionein-human growth hormone fusion genes in transgenic mice results in disproportionate skeletal gigantism. Growth Dev Aging 1991, 55:117–127.PubMedGoogle Scholar
  37. 37.
    Sandstedt J., Ohlsson C., Norjavaara E., Nilsson J. and Tornell J. Disproportional bone growth and reduced weight gain in gonadectomized male bovine growth hormone transgenic and normal mice. Endocrinology 1994, 135:2574–2580.PubMedCrossRefGoogle Scholar
  38. 38.
    Sandstedt J., Törnell I, Norjavaara E., Isaksson O. and Ohlsson C. Intact testis function is a prerequisite for an optimal effect of elevated GH levels on vertebral bone weight in mice. Endocrinology and Metabolism 1996, suppl 1A:10.Google Scholar
  39. 39.
    Sandstedt J., Tornell J., Norjavaara E., Isaksson O.G. and Ohlsson C. Elevated levels of growth hormone increase bone mineral content in normal young mice, but not in ovariectomized mice. Endocrinology 1996, 137:3368–3374.PubMedCrossRefGoogle Scholar
  40. 40.
    Ohlsson C, Tornell J., Sandstedt J. and Andreassen T. Effect of increased growth hormone on mechanical strength of cortical bone in growth hormone-transgenic mice. J Bone Miner Res 1996, suppl 1:T634.Google Scholar
  41. 41.
    Baker A.R., Hollingshead P.G., Pitts-Meek S., Hansen S., Taylor R. and Stewart T.A. Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice. Mol Cell Biol 1992, 12:5541–5547.PubMedGoogle Scholar
  42. 42.
    Saban J., Schneider G.B., Bolt D. and King D. Erythroid-specific expression of human growth hormone affects bone morphology in transgenic mice. Bone 1996, 18:47–52.PubMedCrossRefGoogle Scholar
  43. 43.
    Sass D., Jerome C., Bowman A., Bennett-Cain A., LeRoith D. and Epstein S. Short term effects of GH and IGF-1 on cancellous bone formation in rhesus macaque monkeys. J Clin Endocrinol Metab 1997, 82:1202–1209.PubMedCrossRefGoogle Scholar
  44. 44.
    de Boer H., Blok G.J., van Lingen A., Teule G.J., Lips P. and van der Veen E.A. Consequences of childhood-onset growth hormone deficiency for adult bone mass. Journal of Bone and Mineral Research 1994, 9:1319–1326.PubMedCrossRefGoogle Scholar
  45. 45.
    Kaufman J.M., Taelman P., Vermeiden A. and Vandeweghe M. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab 1992, 74:118–123.PubMedCrossRefGoogle Scholar
  46. 46.
    Saggese G., Baroncelli G.I., Bertelloni S. and Barsanti S. The effect of longterm growth hormone (GH) treatment on bone mineral density in children with GH deficiency. Role of GH in the attainment of peak bone mass. J Clin Endocrinol Metab 1996, 81:3077–3083.PubMedCrossRefGoogle Scholar
  47. 47.
    Wuster C., Slenczka E. and Ziegler R. Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: need for additional growth hormone substitution? Klin Wochenschr 1991, 69:769–773.PubMedCrossRefGoogle Scholar
  48. 48.
    Johansson A.G., Burman P., Westermark K. and Ljunghall S. The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I. J Intern Med 1992, 232:447–452.PubMedCrossRefGoogle Scholar
  49. 49.
    Bing-You R.G., Dems M.C. and Rosen C.J. Low bone mineral density in adults with previous hypothalamic-pituitary tumors: correlations with serum growth hormone responses to GH-releasing hormone, insulin-like growth factor I, and IGF binding protein 3. Calcif Tissue Int 1993, 52:183–187.PubMedCrossRefGoogle Scholar
  50. 50.
    Rosen T., Hansson T., Granhed H., Szucs J. and Bengtsson B.A. Reduced bone mineral content in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh) 1993, 129:201–206.Google Scholar
  51. 51.
    Holmes S.J., Economou G., Whitehouse R.W., Adams J.E. and Shalet S.M. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994, 78:669–674.PubMedCrossRefGoogle Scholar
  52. 52.
    Beshyah S.A., Freemantle C., Thomas E., Rutherford O., Page B., Murphy M. and Johnston D.G. Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults. Clin Endocrinol (Oxf) 1995, 42:179–189.CrossRefGoogle Scholar
  53. 53.
    Degerblad M., Bengtsson B.A., Bramnert M., Johnell O., Manhem P., Rosen T. and Thoren M. Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy. European Journal of Endocrinology 1995, 133:180–188.PubMedCrossRefGoogle Scholar
  54. 54.
    Toogood A.A., Adams J.E., O’Neill P.A. and Shalet S.M. Elderly patients with adult-onset growth hormone deficiency are not osteopenic. J Clin Endocrinol Metab 1997, 82:1462–1466.PubMedCrossRefGoogle Scholar
  55. 55.
    Rosen T., Wilhelmsen L., Landin-Wilhelmsen K., Lappas G. and Bengtsson B. Increased fracture rate in adults with hipopituitarism and growth hormone (GH) deficiency. European Journal of Endocrinology 1997, In PressGoogle Scholar
  56. 56.
    Kotzmann H., Bernecker P., Hubsch P., Pietschmann P., Woloszczuk W., Svoboda T., Geyer G. and Luger A. Bone mineral density and parameters of bone metabolism in patients with acromegaly. Journal of Bone and Mineral Research 1993, 8:459–465.PubMedCrossRefGoogle Scholar
  57. 57.
    Marcus R, Butterfield G., Holloway L., Gilliland L., Baylink D.J., Hintz R.L. and Sherman B.M. Effects of short term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab 1990, 70:519–527.PubMedCrossRefGoogle Scholar
  58. 58.
    Holmes S., Mawer E. and Shalet S. Effect of Growth Hormone Replacement on Calcium, Phosphate, Vitamin D and Parathyroid Hormone Metabolism in Adults with Growth Hormone Deficiency. Endocrinology and Metabolism 1997, 4:49–54.Google Scholar
  59. 59.
    Bengtsson B.A., Eden S., Lonn L., Kvist H., Stokland A, Lindstedt G., Bosaeus I., Tolli J., Sjostrom L. and Isaksson O.G. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab 1993, 76:309–317.PubMedCrossRefGoogle Scholar
  60. 60.
    Beshyah S.A., Thomas E., Kyd P., Sharp P., Fairney A. and Johnston D.G. The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism. Clin Endocrinol (Oxf) 1994, 40:383–391.CrossRefGoogle Scholar
  61. 61.
    Binnerts A, Swart G.R., Wilson J.H., Hoogerbrugge N., Pols H.A., Birkenhager J.C. and Lamberts S.W. The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol (Oxf) 1992, 37:79–87.CrossRefGoogle Scholar
  62. 62.
    Hansen T.B., Brixen K., Vahl N., Jorgensen J.O., Christiansen J.S., Mosekilde L. and Hagen C. Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. J Clin Endocrinol Metab 1996, 81:3352–3359.PubMedCrossRefGoogle Scholar
  63. 63.
    Johannsson G., Rosen T., Bosaeus I., Sjostrom L. and Bengtsson B.A Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency. J Clin Endocrinol Metab 1996, 81:2865–2873.PubMedCrossRefGoogle Scholar
  64. 64.
    Spencer E.M. and Tobiassen O. The mechanism of the action of growth hormone on vitamin D metabolism in the rat. Endocrinology 1981, 108:1064–1070.PubMedCrossRefGoogle Scholar
  65. 65.
    Spanos E., Barrett D., Maclntyre I., Pike J.W., Safilian E.F. and Haussler M.R. Effect of growth hormone on vitamin D metabolism. Nature 1978, 273:246–247.PubMedCrossRefGoogle Scholar
  66. 66.
    Lieberman S.A., Holloway L., Marcus R. and Hoffman AR. Interactions of growth hormone and parathyroid hormone in renal phosphate, calcium, and calcitriol metabolism and bone remodeling in postmenopausal women. Journal of Bone and Mineral Research 1994, 9:1723–1728.PubMedCrossRefGoogle Scholar
  67. 67.
    Whitehead H.M., Boreham C., Mcllrath E.M., Sheridan B., Kennedy L., Atkinson A.B. and Hadden D.R. Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled crossover study. Clin Endocrinol (Oxf) 1992, 36:45–52.CrossRefGoogle Scholar
  68. 68.
    Thoren M, Soop M., Degerblad M. and Saaf M. Preliminary study of the effects of growth hormone substitution therapy on bone mineral density and serum osteocalcin levels in adults with growth hormone deficiency. Acta Endocrinol (Copenh) 1993, 128:41–43.Google Scholar
  69. 69.
    Vandeweghe M., Taelman P. and Kaufman J.M. Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males. Clin Endocrinol (Oxf) 1993, 39:409–415.CrossRefGoogle Scholar
  70. 70.
    Amato G., Carella C., Fazio S., La Montagna G., Cittadini A., Sabatini D., Marciano-Mone C., Sacca L. and Bellastella A. Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993, 77:1671–1676.PubMedCrossRefGoogle Scholar
  71. 71.
    Balducci R., Toscano V., Pasquino A.M., Mangiantini A., Municchi G, Armenise P., Terracina S., Prossomariti G. and Boscherini B. Bone turnover and bone mineral density in young adult patients with panhypopituitarism before and after long-term growth hormone therapy. European Journal of Endocrinology 1995, 132:42–46.PubMedCrossRefGoogle Scholar
  72. 72.
    Sartorio A., Ortolani S., Conti A., Cherubim R., Galbiati E. and Faglia G. Effects of recombinant growth hormone (GH) treatment on bone mineral density and body composition in adults with childhood onset growth hormone deficiency. J Endocrinol Invest 1996, 19:524–529.PubMedGoogle Scholar
  73. 73.
    Degerblad M, Elgindy N., Hall K., Sjoberg H.E. and Thoren M. Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. Acta Endocrinol (Copenh) 1992, 126:387–393.Google Scholar
  74. 74.
    Juul A., Pedersen S.A., Sorensen S., Winkler K., Jorgensen J.O., Christiansen J.S. and Skakkebaek N.E. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline Phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset. European Journal of Endocrinology 1994, 131:41–49.PubMedCrossRefGoogle Scholar
  75. 75.
    O’Halloran D.J., Tsatsoulis A., Whitehouse R.W., Holmes S.J., Adams J.E. and Shalet S.M. Increased bone density after recombinant human growth hormone (GH) therapy in adults with isolated GH deficiency. J Clin Endocrinol Metab 1993, 76:1344–1348.PubMedCrossRefGoogle Scholar
  76. 76.
    Holmes S.J., Whitehouse R.W., Swindell R., Economou G., Adams J.E. and Shalet S.M. Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency. Clin Endocrinol (Oxf) 1995, 42:627–633.CrossRefGoogle Scholar
  77. 77.
    Beshyah S.A., Kyd P., Thomas E., Fairney A. and Johnston D.G. The effects of prolonged growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults. Clin Endocrinol (Oxf) 1995, 42:249–254.CrossRefGoogle Scholar
  78. 78.
    Baum H.B., Biller B.M., Finkelstein J.S., Cannistraro K.B., Oppenhein D.S., Schoenfeld D.A., Michel T.H., Wittink H. and Klibanski A. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med 1996, 125:883–890.PubMedGoogle Scholar
  79. 79.
    Brixen K., Nielsen H.K., Mosekilde L. and Flyvbjerg A. A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers. Journal of Bone and Mineral Research 1990, 5:609–618.PubMedCrossRefGoogle Scholar
  80. 80.
    Brixen K., Kassem M., Nielsen H.K., Loft A.G., Flyvbjerg A. and Mosekilde L. Short-term treatment with growth hormone stimulates osteoblastic and osteoclastic activity in osteopenic postmenopausal women: a dose response study. Journal of Bone and Mineral Research 1995, 10:1865–1874.PubMedCrossRefGoogle Scholar
  81. 81.
    Kassem M., Brixen K., Blum W.F., Mosekilde L. and Eriksen E.F. Normal osteoclastic and osteoblastic responses to exogenous growth hormone in patients with postmenopausal spinal osteoporosis. Journal of Bone and Mineral Research 1994, 9:1365–1370.PubMedCrossRefGoogle Scholar
  82. 82.
    Kruse H.P. and Kuhlencordt F. On an attempt to treat primary and secondary osteoporosis with human growth hormone. Horm Metab Res 1975, 7:488–491.PubMedCrossRefGoogle Scholar
  83. 83.
    Aloia J.F., Zanzi I, Ellis K., Jowsey J., Roginsky M., Wallach S. and Conn S.H. Effects of growth hormone in osteoporosis. J Clin Endocrinol Metab 1976, 43:992–999.PubMedCrossRefGoogle Scholar
  84. 84.
    Aloia J.F., Vaswani A., Kapoor A., Yeh J.K. and Cohn S.H. Treatment of osteoporosis with calcitonin, with and without growth hormone. Metabolism 1985, 34:124–129.PubMedCrossRefGoogle Scholar
  85. 85.
    Aloia J.F., Vaswani A., Meunier RI, Edouard C.M., Arlot M.E., Yeh J.K. and Cohn S.H. Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin. Calcif Tissue Int 1987, 40:253–259.PubMedCrossRefGoogle Scholar
  86. 86.
    Holloway L., Kohlmeier L., Kent K. and Marcus R. Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women. J Clin Endocrinol Metab 1997, 82:1111–1117.PubMedCrossRefGoogle Scholar
  87. 87.
    Rudman D., Feller A.G., Nagraj H.S., Gergans G.A., Lalitha P.Y., Goldberg A.F., Schlenker RA., Conn L., Rudman I.W. and Mattson D.E. Effects of human growth hormone in men over 60 years old N Engl J Med 1990, 323:1–6.Google Scholar
  88. 88.
    Johansson A.G., Lindh E. and Ljunghall S. Insulin-like growth factor I stimulates bone turnover in osteoporosis. Lancet 1992, 339:1619.PubMedCrossRefGoogle Scholar
  89. 89.
    Ebeling P.R., Jones J.D., O’Fallon W.M., Janes C.H. and Riggs B.L. Shortterm effects of recombinant human insulin-like growth factor I on bone turnover in normal women. J Clin Endocrinol Metab 1993, 77:1384–1387.PubMedCrossRefGoogle Scholar
  90. 90.
    Ghiron L.J., Thompson J.L., Holloway L., Hintz R.L., Butterfield G.E., Hoffman A.R. and Marcus R. Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women. Journal of Bone and Mineral Research 1995, 10:1844–1852.PubMedCrossRefGoogle Scholar
  91. 91.
    Johansson A.G., Lindh E., Blum W.F., Kollerup G., Sorensen O.H. and Ljunghall S. Effects of growth hormone and insulin-like growth factor I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 1996, 81:44–48.PubMedCrossRefGoogle Scholar
  92. 92.
    Hedner E., Linde A. and Nilsson A. Systemically and locally administered growth hormone stimulates bone healing in combination with osteopromotive membranes: an experimental study in rats. Journal of Bone and Mineral Research 1996, 11:1952–1960.PubMedCrossRefGoogle Scholar
  93. 93.
    Tseng K.F., Bonadio J.F., Stewart T.A., Baker A.R. and Goldstein S.A. Local expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice. J Orthop Res 1996, 14:598–604.PubMedCrossRefGoogle Scholar
  94. 94.
    Ejersted C., Andreassen T.T., Hauge E.M., Meisen F. and Oxlund H. Parathyroid hormone (1–34) increases vertebral bone mass, compressive strength, and quality in old rats. Bone 1995, 17:507–511.PubMedCrossRefGoogle Scholar
  95. 95.
    Ejersted C., Andreassen T.T., Nilsson M.H. and Oxlund H. Human parathyroid hormone(l-34) increases bone formation and strength of cortical bone in aged rats. European Journal of Endocrinology 1994, 130:201–207.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Claes Ohlsson
    • 1
    • 2
  1. 1.Research Centre for Endocrinology and MetabolismSahlgrenska University HospitalGöteborgSweden
  2. 2.Diabetes BranschNIDDK, NIHBethesdaUSA

Personalised recommendations