Skip to main content
SpringerLink
Log in

Mechanical properties, bone mineral content, and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: Influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment

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

Summary

Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or Stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on Serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the Start of the experiment) were Studied for 6 months. The results were compared with those obtained in agematched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of Serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were Significantly reduced.

Treatment of OVX rats with 1 mg ND/14 days resulted in a Significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and Strength, and bone IGF-I content, and a decrease in Serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVX to the level of the intact controls.

These results indicate that ND acts as an antiresorptive drug and as a bone formation Stimulating drug. Furthermore, the increased bone mass and bone mineral density is associated with improved bone Strength and stiffness and the presence of an increased amount of IGF-I. IGF-I is a growth factor considered to play a role in the maintenance of normal skeletal balance by a paracrine or autocrine mechanism.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Riggs BL, Hodgson SF, O'Fallon WM, Chao EYS, Wahner HW, Muks JM, Cedel SL, Melton III LJ (1990) Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 322:802–809

    Google Scholar 

  2. Geusens P, Dequeker J (1986) Long-term effect of nandrolone decanoate, 1α-hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: a double-blind controlled study. Bone Miner 1:347–357

    Google Scholar 

  3. Johansen JS, Hassager C, Podenphant J, Riis BJ, Hartwell D, Thomsen K, Christiansen C (1989) Treatment of postmenopausal osteoporosis: Is the anabolic steroid nandrolone decanoate a candidate? Bone Miner 6:77–86

    Google Scholar 

  4. Need AG, Horowitz M, Bridges A, Morris HA, Nordin BEC (1989) Effects of nandrolone decanoate and antiresorptive therapy on vertebral density in osteoporotic postmenopausal women. Arch Intern Med 149:57–60

    Google Scholar 

  5. Adami S, Fossaluzza V, Rossini M, Bertoldo F, Gatti D, Zamberlan N, LoCascio V (1991) The prevention of corticosteroidinduced osteoporosis with nandrolone decanoate. Bone Miner 15:72–81

    Google Scholar 

  6. Hassager C, Riis BJ, Pødenphant J, Christiansen C (1989) Nandrolone decanoate treatment of post-menopausal osteoporosis for 2 years and effects of withdrawal. Maturitas 11:305–317

    Google Scholar 

  7. Colvard DS, Eriksen ED, Keetin PE, Wilson EM, Lubahn DB, French FS, Riggs BL, Spelsberg TC (1989) Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci USA 86:854–857

    Google Scholar 

  8. Kasperk CH, Wergedal JE, Farley JR, Linkhart TA, Turner RT, Baylink DJ (1989) Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology 124:1576–1578

    Google Scholar 

  9. Fitzsimmons RJ, Wergedal JE, Kasperk C, Baylink DJ (1990) The effects of nandrolone decanoate on human bone cells, in vitro. In: Christiansen C (ed) Osteoporosis 1990: the role of nandrolone decanoate in the treatment of established osteoporosis. Handeltrijkkeriet Aalborg Aps., Aalborg, Denmark, pp 13–18

    Google Scholar 

  10. Raymaekers G, Aerssens J, Van den Eynde R, Peeters J, De Keersmaecker G, Geusens P, Dequeker J (1992) Changes in bone matrix constituents in ovariectomized dogs on a calciumdeficient diet after administration of 17β-oestradiol and nandrolone decanoate. Eur J Exp Musculoskel Res 1:72–76

    Google Scholar 

  11. Kivirikko KI, Laitinen O, Prockop DJ (1967) Modifications of a specific assay for hydroxyproline in urine. Anal Biochem 19:249–255

    Google Scholar 

  12. Verhaeghe J, Van Herck E, Van Bree R, Van Assche FA, Bouillon R (1990) Osteocalcin during the reproductive cycle in normal and diabetic rats. J Endocrinol 120:143–151

    Google Scholar 

  13. Gundberg CM, Hauschka P, Lian JB, Gallop PM (1984) Osteocalcin: isolation, characterization and detection. In: Molav K (ed) Methods in enzymology. Academic Press, New York, pp 516–544

    Google Scholar 

  14. Verhaeghe J, Van Herck E, Visser WJ, Suiker AMH, Thomasset M, Einhorn TA, Faierman E, Bouillon R (1990) Bone and mineral metabolism in BB rats with long-term diabetes. Diabetes 39:249–255

    Google Scholar 

  15. Geusens P (1992) Photon absorptiometry in osteoporosis: bone mineral measurements in animal models and in humans. PhD thesis, K.U. Leuven, Orientaliste, Belgium

    Google Scholar 

  16. Mbuyi-Muamba JM, Dequeker J (1986) Bone mass measured by photonabsorptiometry and radiogrammetry in Wistar rats: age and sex variations. Invest Radiol 21:336–339

    Google Scholar 

  17. Burstein AH, Frankel VH (1971) A standard test for laboratory animal bone. J Biomechanics 4:155–158

    Google Scholar 

  18. Martens M, Van Audekercke R, De Meester P, Mulier JC (1980) The mechanical characteristics of the long bones of the lower extremity in torsional loading. J Biomechanics 13:667–676

    Google Scholar 

  19. Wronski TJ, Cintron M, Doherty AL, Dann LM (1988) Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. Endocrinology 123:681–686

    Google Scholar 

  20. Frost HM, Jee WSS (1992) On the rat model of human osteopenias and osteoporoses. Bone Miner 18:227–236

    Google Scholar 

  21. Schot LPC, Schuurs AHWM (1990) Pathophysiology of bone loss in castrated animals. J Steroid Biochem Molec Biol 37:461–465

    Google Scholar 

  22. Baron R, Tross R, Vipnery A (1984) Evidence of sequential remodeling in rat trabecular bone: morphology, dynamic histomorphometry, and changes during skeletal maturation. Anat Rec 208:127–145

    Google Scholar 

  23. Wronski TJ, Schenck PA, Cintron M, Walsh CC (1987) Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue Int 40:155–159

    Google Scholar 

  24. Turner RT, Wakky GK, Hannon KS (1990) Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats. J Orthop Res 8:612–617

    Google Scholar 

  25. Tang LY, Jee WSS, Ke HZ, Kimmel DB (1992) Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure. J Bone Miner Res 7:1093–1104

    Google Scholar 

  26. Vanderschueren D, Gevers G, Raymaekers G, Devos P, Dequeker J (1990) Sex- and age-related changes in bone and serum osteocalcin. Calcif Tissue Int 46:179–182

    Google Scholar 

  27. Dequeker J (1972) Bone loss in normal and pathological conditions. PhD Thesis, K. U. Leuven, Leuven University Press, Belgium

    Google Scholar 

  28. Dannucci GA, Martin RB, Patterson-Buckendahl (1987) Ovariectomy and trabecular bone remodeling in the dog. Calcif Tissue Int 40:194–199

    Google Scholar 

  29. Ismail F, Epstein S, Fallon MD, Thosmas SB, Reinhardt TA (1988) Serum bone gla protein and the vitamin D endocrine system in the oophorectomized rat. Endocrinology 122:624–630

    Google Scholar 

  30. Wronski TJ, Cintron M, Dann LM (1988) Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183

    Google Scholar 

  31. Delmas PD, Stenner S, Wahner HW, Mann KG, Riggs BL (1983) Increase in serum bone gamma-carboxyglutamic acid protein with aging in women. J Clin Invest 71:1316–1321

    Google Scholar 

  32. Yamamoto H, Sohmiya M, Oka N, Kato Y (1991) Effects of aging and sex on plasma insulin-like growth factor I (IGF-I) levels in normal adults. Acta Endocrinol (Copenh) 124:497–500

    Google Scholar 

  33. Wronski TJ, Dann LM, Horner SL (1989) Time course of vertebral osteopenia in ovariectomized rats. Bone 10:295–301

    Google Scholar 

  34. Wronski TJ, Dann LM, Scott KS, Cintrón M (1989) Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45:360–366

    Google Scholar 

  35. Fröhlander N, von Schoultz B (1988) Growth hormone and somatomedin C during post-menopausal replacement therapy with oestrogen alone and in combination with an antioestrogen. Maturitas 9:297–302

    Google Scholar 

  36. Turner RT, Backup P, Kline BC, Colvard DS, Spelsberg TC (1991) Evidence that the inhibition of osteoblast activity by estrogen is preceded by down regulation of IGF-I gene expression and that these changes are estrogen-receptor mediated. In: Spencer EM (ed) Modern concepts of insulin-like growth factors. Elsevier Science Publishing Co, New York, pp 143–153

    Google Scholar 

  37. Underwood LE, D'Ercole AJ, Clemmons DR, Van Wyk JJ (1986) Paracrine functions of somatomedin. In: Franchimont P (ed). Clinics in endocrinology and metabolism: paracrine control, vol 15. WB Saunders Co, London, pp 59–77

    Google Scholar 

  38. Holly JMP, Wass JAH (1989) Insulin-like growth factors: autocrine, paracrine or endocrine? New perspectives of the somatomedin hypothesis in the light of recent developments. J Endocrinol 122:611–618

    Google Scholar 

  39. Finkelman RD, Eason AL, Bell NH, Baylink DJ (1991) Ovariectomy selectively reduces the concentration of transforming growth factor beta in rat bone (abstract). J Bone Miner Res 6 (suppl 1), S99

    Google Scholar 

  40. McCarthy TL, Centrella M, Canalis E (1989) Insulin-like growth factor (IGF) and bone. Connect Tissue Res 20:277–282

    Google Scholar 

  41. Isaksson OGP, Lindahl A, Nilsson A, Isgaard J (1987) Mechanisms of the stimulatory effect of growth hormone on longitudinal bone growth. Endocrine Rev 8:426–438

    Google Scholar 

  42. Ibbotson KJ, Orcutt CM, D'Soua SM, Paddock CL, Arthur JA, Jankowsky ML, Boyce RW (1992) Contrasting effects of parathyroid hormone and insulin-like growth factor I in an aged ovariectomized rat model of postmenopausal osteoporosis. J Bone Miner Res 7:425–432

    Google Scholar 

  43. Spencer EM, Lin CC, Si ECC, Howard GA (1990) In vivo actions of insulin-like growth factor I (IGF-I) on bone formation and resorption in rats. Bone 12:21–27

    Google Scholar 

  44. Geusens P, Schot LPC, Nijs J, Dequeker J (1991) Calciumdeficient diet in ovariectomized dogs limits the effects of 17β-estradiol and nandrolone decanoate on bone. J Bone Miner Res 6:791–797

    Google Scholar 

  45. Schot LPC, Brunekreef K, Spanjers C, Bouillon R (1990) Anabolic and anti-catabolic effects of nandrolone decanoate (Deca-Durabolin®) on bone of ovariectomized rats. In: Christiansen C (ed). Osteoporosis 1990: the role of nandrolone decanoate in the treatment of established osteoporosis. Handeltrijkkeriet Aalborg Aps., Aalborg, Denmark, pp 19–23

    Google Scholar 

  46. Geusens P, Cantatore F, Nijs J, Proesmans W, Emma F, Dequeker J (1991) Heterogeneity of growth of bone in children at the spine, radius and total skeleton. Growth Dev Aging 55:249–256

    Google Scholar 

  47. Ishak KG, Zimmerman HJ (1987) Hepatotoxic effects of the anabolic/androgenic steroids. Semin Liver Dis 7:230–236

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Arthritis and Metabolic Bone Disease Research Unit, K.U. Leuven, U.Z. Pellenberg, B-3212, Pellenberg, Belgium

    Jeroen Aerssens, Piet Geusens, Amin Abdel-Hamid Osman & Jan Dequeker

  2. Laboratory for Biomechanics, K.U. Leuven, U.Z. Pellenberg, B-3212, Pellenberg, Belgium

    Remy Van Audekercke

  3. Scientific Development Group, Organon International BV, Oss, The Netherlands

    Lodewijk P. C. Schot

Authors
  1. Jeroen Aerssens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Remy Van Audekercke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piet Geusens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lodewijk P. C. Schot
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amin Abdel-Hamid Osman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jan Dequeker
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aerssens, J., Van Audekercke, R., Geusens, P. et al. Mechanical properties, bone mineral content, and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: Influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment. Calcif Tissue Int 53, 269–277 (1993). https://doi.org/10.1007/BF01320913

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01320913

Key words

Search

Navigation