Skip to main content

Advertisement

Log in

Local Anabolic Effects of Growth Hormone on Intact Bone and Healing Fractures in Rats

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

The local effects of rat growth hormone (rGH) injected at the surfaces of intact tibial diaphyses and healing tibial diaphysial fractures were investigated in 10-month-old female rats. Intact diaphysial bones: rats were injected daily for 14 days with vehicle, 2 µg rGH, or 20 µg rGH at the surface of the right tibial diaphysis. After 10 days of injection the animals were labeled with calcein. At the rGH-injected location, increased external diaphysial bone dimensions and increased calcein-labeled area were seen, and the responses to rGH were dose dependent. The new bone formed at the periosteal surface was woven bone. At the opposite left tibia, no systemic effect of rGH was found. rGH did not influence body weight changes during the treatment, or muscle mass or serum IGF-I at the end of the treatment. Healing diaphysial fractures: a closed fracture was made in the right tibial diaphysis, and stabilized by medullary nailing. The fractures were tested after 21 days and 98 days of healing. During the first 21 days of healing, all rats were injected daily with either vehicle or 20 µg rGH at the surface of the fracture line. In the 21-day healing rGH group, ultimate load, ultimate stiffness, external callus dimensions, and external callus volume of the fractures were increased. rGH did not affect body weight changes during this healing period or serum IGF-I at the end of the healing period. In the 98-day healing rGH group, ultimate load was still increased compared with the vehicle group, although a ninefold increase took place in the vehicle group between days 21 and 98 of healing. External callus dimensions of the fractures were increased in the rGH group, whereas body weight changes during the healing period were not affected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. TT Andreassen PH Jørgensen A Flyvbjerg H Ørskov H Oxlund (1995) ArticleTitleGrowth hormone stimulates bone formation and strength of cortical bone in aged rats. J Bone Miner Res 10 1057–1067 Occurrence Handle1:CAS:528:DyaK2MXntVakt7w%3D Occurrence Handle7484281

    CAS  PubMed  Google Scholar 

  2. G Ørtoft TT Andreassen H Oxlund (1999) ArticleTitleGrowth hormone increases cortical and cancellous bone mass in young growing rats with glucocorticoid-induced osteopenia. J Bone Miner Res 14 710–721

    Google Scholar 

  3. I Morimoto K Kai Y Okada et al. (2000) ArticleTitleSkeletal changes in rats bearing mammosomatotrophic pituitary tumors: a model of acromegaly with gonadal dysfunction. Bone 26 255–261 Occurrence Handle10.1016/S8756-3282(99)00274-4 Occurrence Handle1:CAS:528:DC%2BD3cXhtFalsrg%3D Occurrence Handle10709998

    Article  CAS  PubMed  Google Scholar 

  4. TT Andreassen H Oxlund (2000) ArticleTitleThe influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats. J Bone Miner Res 15 2266–2275

    Google Scholar 

  5. Li Mosekilde JS Thomsen PB Orhii DN Kalu (1998) ArticleTitleGrowth hormone increases vertebral and femoral bone strength in osteopenic, ovariectomized, aged rats in a dose-dependent and site-specific manner. Bone 23 343–352 Occurrence Handle10.1016/S8756-3282(98)00107-0 Occurrence Handle1:CAS:528:DyaK1cXmsFeit7w%3D Occurrence Handle9763146

    Article  CAS  PubMed  Google Scholar 

  6. Li Mosekilde L Tornvig JS Thomsen PB Orhii MJ Banu DN Kalu (2000) ArticleTitleParathyroid hormone and growth hormone have additive or synergetic effect when used as intervention treatment in ovariectomized rats with established osteopenia. Bone 26 643–651 Occurrence Handle10.1016/S8756-3282(00)00276-3 Occurrence Handle1:CAS:528:DC%2BD3cXjsVGgsLw%3D Occurrence Handle10831937

    Article  CAS  PubMed  Google Scholar 

  7. B Bak PH Jørgensen TT Andreassen (1990) ArticleTitleDose response of growth hormone on fracture healing in the rat. Acta Orthop Scand 61 54–57 Occurrence Handle1:STN:280:By%2BB2cnpvFE%3D Occurrence Handle2336953

    CAS  PubMed  Google Scholar 

  8. B Bak PH Jørgensen TT Andreassen (1991) ArticleTitleThe stimulating effect of growth hormone on fracture healing is dependent on onset and duration of administration. Clin Orthop 264 295–301 Occurrence Handle1997248

    PubMed  Google Scholar 

  9. G Ørtoft H Grønbæk H Oxlund (1998) ArticleTitleGrowth hormone administration can improve growth in glucocorticoid-injected rats without affecting the lymphocytopenic effect of the glucocorticoid. Growth Horm IGF Res 8 251–264 Occurrence Handle10984314

    PubMed  Google Scholar 

  10. H Oxlund NB Andersen G Ørtoft H Ørskov TT Andreassen (1998) ArticleTitleGrowth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats. Endocrinology 139 1899–1904 Occurrence Handle1:CAS:528:DyaK1cXitVKltrY%3D Occurrence Handle9528976

    CAS  PubMed  Google Scholar 

  11. JH Tobias JWM Chow TJ Chambers (1992) ArticleTitleOpposite effects of insulin-like growth factor-I on the formation of trabecular and cortical bone in adult female rats. Endocrinology 131 2387–2392 Occurrence Handle1:CAS:528:DyaK3sXhsVyr Occurrence Handle1425437

    CAS  PubMed  Google Scholar 

  12. EM Spencer CC Liu ECC Si GA Howard (1991) ArticleTitleIn vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats. Bone 12 21–26 Occurrence Handle1:STN:280:By6B2svhtVA%3D Occurrence Handle2054232

    CAS  PubMed  Google Scholar 

  13. HN Rosen V Chen A Cittadini et al. (1995) ArticleTitleTreatment with growth hormone and IGF-I in growing rats increases bone mineral content but not bone mineral density. J Bone Miner Res 10 1352–1358

    Google Scholar 

  14. AG Torrance JR Mosley RFL Suswillo LE Lanyon (1994) ArticleTitleNoninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periostal pressure. Calcif Tissue Int 54 241–247 Occurrence Handle1:STN:280:ByuA3s3ntVU%3D Occurrence Handle8055374

    CAS  PubMed  Google Scholar 

  15. MZ Cheng G Zaman LE Lanyon (1994) ArticleTitleEstrogen enhances the stimulation of bone collagen synthesis by loading and exogenous prostacyclin, but not prostaglandin E2, in organ cultures of rat ulnae. J Bone Miner Res 9 805–816

    Google Scholar 

  16. NB Andersen TT Andreassen H Ørskov H Oxlund (2000) ArticleTitleGrowth hormone and mild exercise in combination increases markedly muscle mass and tetanic tension in old rats. Eur J Endocrinol 143 409–418 Occurrence Handle1:CAS:528:DC%2BD3cXntVShs7g%3D Occurrence Handle11022185

    CAS  PubMed  Google Scholar 

  17. BP Halloran DD Bikle J Harris et al. (1995) ArticleTitleSkeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone. J Bone Miner Res 10 1168–1176

    Google Scholar 

  18. TT Andreassen C Ejersted H Oxlund (1999) ArticleTitleIntermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 14 960–968

    Google Scholar 

  19. H Grønbæk B Nielsen R Østerby A Harris H Ørskov A Flyvbjerg (1995) ArticleTitleEffect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats. Diabetologia 38 135–144 Occurrence Handle10.1007/s001250050263 Occurrence Handle7536170

    Article  PubMed  Google Scholar 

  20. PH Jørgensen C Bang TT Andreassen A Flyvbjerg H Ørskov (1995) ArticleTitleDose-response study of the effect of growth hormone on mechanical properties of skin graft wounds. J Surg Res 58 295–301 Occurrence Handle10.1006/jsre.1995.1046 Occurrence Handle7885026

    Article  PubMed  Google Scholar 

  21. JA Gasser CP Jerome (1992) ArticleTitleParathyroid hormone: a cure for osteoporosis? Triangle 31 111–121

    Google Scholar 

  22. E Hedner A Linde A Nilsson (1996) ArticleTitleSystemically and locally administered growth hormone stimulates bone healing in combination with osteopromotive membranes: an experimental study in rats. J Bone Miner Res 11 1952–1960

    Google Scholar 

  23. J Guicheux O Gauthier E Aguado et al. (1998) ArticleTitleHuman growth hormone locally released in bone sites by calcium-phosphate biomaterial stimulates ceramic bone substitution without systemic effects: a rabbit study. J Bone Miner Res 13 739–748

    Google Scholar 

  24. J Isgaard A Nilsson A Lindahl JO Jansson OG Isaksson (1986) ArticleTitleEffects of local administration of GH and IGF-1 on longitudinal bone growth in rats. Am J Physiol 250 E367–E372 Occurrence Handle1:CAS:528:DyaL28XktVSqsbk%3D Occurrence Handle3963179

    CAS  PubMed  Google Scholar 

  25. NL Schlechter SM Russel EM Spencer CS Nicoll (1986) ArticleTitleEvidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin. Proc Natl Acad Sci USA 83 7932–7934

    Google Scholar 

  26. NL Schlechter SM Russel S Greenberg EM Spencer CS Nicoll (1986) ArticleTitleA direct growth effect of growth hormone in rat hindlimb shown by arterial infusion. Am J Physiol 250 E231–E235 Occurrence Handle1:CAS:528:DyaL28XhvVSnsbw%3D Occurrence Handle3953810

    CAS  PubMed  Google Scholar 

  27. A Nilsson J Isgaard A Lindahl L Peterson O Isaksson (1987) ArticleTitleEffects of unilateral arterial infusion of GH and IGF-I on tibial longitudinal bone growth in hypophysectomized rats. Calcif Tissue Int 40 91–96 Occurrence Handle3105839

    PubMed  Google Scholar 

  28. AR Baker PG Hollingshead S Pitts Meek S Hansen R Taylor TA Stewart (1992) ArticleTitleOsteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice. Mol Cell Biol 12 5541–5547 Occurrence Handle1:CAS:528:DyaK3sXhs1Kisg%3D%3D Occurrence Handle1448085

    CAS  PubMed  Google Scholar 

  29. K-F Tseng JF Bonadio TA Stewart AR Baker SA Goldstein (1996) ArticleTitleLocal expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice. J Orthop Res 14 598–604 Occurrence Handle1:CAS:528:DyaK28XlvVWgsr0%3D Occurrence Handle8764869

    CAS  PubMed  Google Scholar 

  30. J Saban GB Schneider D Bolt D King (1996) ArticleTitleErythroid-specific expression of human growth hormone affects bone morphology in transgenic mice. Bone 18 47–52 Occurrence Handle10.1016/8756-3282(95)00419-X Occurrence Handle1:CAS:528:DyaK28XhsFKmtLc%3D Occurrence Handle8717536

    Article  CAS  PubMed  Google Scholar 

  31. R Barnard KW Ng TJ Martin MJ Waters (1991) ArticleTitleGrowth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. Endocrinology 128 1459–1464 Occurrence Handle1:CAS:528:DyaK3MXhsFOns7o%3D Occurrence Handle1999164

    CAS  PubMed  Google Scholar 

  32. A Nilsson D Swolin S Enerback C Ohlsson (1995) ArticleTitleExpression of functional growth hormone receptors in cultured human osteoblast-like cells. J Clin Endocrinol Metab 80 3483–3488 Occurrence Handle1:CAS:528:DyaK2MXpvFSjtLw%3D Occurrence Handle8530587

    CAS  PubMed  Google Scholar 

  33. MC Slootweg JP Salles C Ohlsson CP De Vries MJE Engelbregt JC Netelenbos (1996) ArticleTitleGrowth hormone binds to a single high affinity receptor site on mouse osteoblasts: modulation by retinoic acid and cell differentiation. J Endocrinol 150 465–472 Occurrence Handle1:CAS:528:DyaK28XmtVSiur4%3D Occurrence Handle8882165

    CAS  PubMed  Google Scholar 

  34. M Ernst ER Froesch (1988) ArticleTitleGrowth hormone-dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor I. Biochem Biophys Res Commun 151 142–147 Occurrence Handle1:CAS:528:DyaL1cXhsVekt78%3D Occurrence Handle3348770

    CAS  PubMed  Google Scholar 

  35. M Ernst GA Rodan (1990) ArticleTitleIncreased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3. Endocrinology 127 807–814 Occurrence Handle1:CAS:528:DyaK3cXlt1Kkur8%3D Occurrence Handle2164921

    CAS  PubMed  Google Scholar 

  36. MC Slootweg SC Van Buul-Offers MPM Herrmann-Erlee JM van der Meer SA Duursma (1988) ArticleTitleGrowth hormone is mitogenic for fetal mouse osteoblasts but not for undifferentiated bone cells. J Endocrinol 116 R11–R13 Occurrence Handle1:CAS:528:DyaL1cXht1CrsLw%3D Occurrence Handle3351425

    CAS  PubMed  Google Scholar 

  37. G Morel P Chavassieux B Barenton PM Dubois PJ Meunier G Boivin (1993) ArticleTitleEvidence for a direct effect of growth hormone on osteoblasts. Cell Tissue Res 273 279–286 Occurrence Handle1:CAS:528:DyaK3sXmtFOku7o%3D Occurrence Handle8364969

    CAS  PubMed  Google Scholar 

  38. M Kassem W Blum J Ristelli L Mosekilde EF Eriksen (1993) ArticleTitleGrowth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro. Calcif Tissue Int 52 222–226 Occurrence Handle1:CAS:528:DyaK3sXkt1Skurs%3D Occurrence Handle7683248

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to A. Berg, M. Fischer, and J. Utoft for excellent technical assistance. We thank K. Nyborg, Medical Research Laboratories, Aarhus University Hospital for performing the IGF-I determinations. This work was supported by The Danish Health Research Council, grant #9600822 (Aarhus University-Novo Nordisk Center for Research in Growth and Regeneration), and Aarhus University Research Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. T. Andreassen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andreassen, T., Oxlund, H. Local Anabolic Effects of Growth Hormone on Intact Bone and Healing Fractures in Rats . Calcif Tissue Int 73, 258–264 (2003). https://doi.org/10.1007/s00223-002-2074-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-002-2074-6

Keywords

Navigation