Skip to main content

Advertisement

Log in

Disuse and orchidectomy have additional effects on bone loss in the aged male rat

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Introduction

A severely osteopenic rat model was obtained by combining orchidectomy (ORX) and disuse (due to local paralysis induced by botulinum toxin [BTX] in the quadriceps muscle).

Methods

Forty-two aged male rats (5–6 months old) were randomized into three groups: 18 were SHAM operated; 6 were ORX; and 18 were ORX and BTX injected in the right hindlimb. One, two, and three months after surgery, bone mass (BV/TV) and microarchitectural parameters (Tb.Th, Tb.N, Tb.Sp, Tb.Pf, and structure model index [SMI]) were measured by microcomputed tomography (microCT) on the primary and secondary spongiosa of the femur. Osteoid parameters (OS/BS, O.Th), the number of osteoclasts (Nb.Oc), and the mineral apposition rate (Ct.MAR, Cn.MAR) were measured by histology. The serum tartrate-resistant acid phosphatase (TRAcP) 5b activity was measured by immunoassay.

Results

ORX induced a decrease of BV/TV, Tb.N and an increase of Tb.Sp, Tb.Pf, and SMI on both primary and secondary spongiosa. ORX and BTX had cumulative effects on bone loss, since differences were maximized on the right femur. The decrease in BV/TV reached −65%. Osteoid parameters and mineral apposition rate increased during the time course of the study. A peak of serum TRAcP was found at 7 days post-ORX. TRAcP levels reached the highest values in the ORX-BTX groups and the effect lasted longer than in the group with ORX alone. The association of ORX-BTX induced a greater bone resorption, due to the removal of complete trabeculae, compared to ORX alone.

Conclusion

This model induced a severe and rapid bone loss and can be used to explore pharmacological- and biomaterial-based countermeasures.

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.

Fig. 1a–c
Fig. 2

Similar content being viewed by others

References

  1. Anonymous (1993) Consensus Development Conference on Osteoporosis. Hong Kong, April 1–2, 1993. Am J Med 95(5A):1–78

    Google Scholar 

  2. Boonen S, Vanderschueren D, Cheng XG, Verbeke G, Dequeker J, Geusens P, Broos P, Bouillon R (1997) Age-related (type II) femoral neck osteoporosis in men: biochemical evidence for both hypovitaminosis D- and androgen deficiency-induced bone resorption. J Bone Miner Res 12(12):2119–2126

    Article  PubMed  CAS  Google Scholar 

  3. Minaire P, Neunier P, Edouard C, Bernard J, Courpron P, Bourret J (1974) Quantitative histological data on disuse osteoporosis: comparison with biological data. Calcif Tissue Res 17(1):57–73

    Article  PubMed  CAS  Google Scholar 

  4. Kannus P, Jarvinen M, Sievanen H, Jarvinen TA, Oja P, Vuori I (1994) Reduced bone mineral density in men with a previous femur fracture. J Bone Miner Res 9(11):1729–1736

    Article  PubMed  CAS  Google Scholar 

  5. Chappard D, Alexandre C, Vico L, Palle S, Riffat G (1985) Amputation-induced osteoporosis: a new model to explore the effects of weightlessness on the human skeleton. In: Proceedings of the 2nd International Conference on Space Physiology, Toulouse, France, November 1985

  6. Hodkinson HM, Brain AT (1967) Unilateral osteoporosis in longstanding hemiplegia in the elderly. J Am Geriatr Soc 15(1):59–64

    PubMed  CAS  Google Scholar 

  7. Gregg EW, Pereira MA, Caspersen CJ (2000) Physical activity, falls, and fractures among older adults: a review of the epidemiologic evidence. J Am Geriatr Soc 48(8):883–893

    PubMed  CAS  Google Scholar 

  8. Prior JC, Barr SI, Chow R, Faulkner RA (1996) Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 5. Physical activity as therapy for osteoporosis. CMAJ 155(7):940–944

    PubMed  CAS  Google Scholar 

  9. Orwoll ES (2004) Treatment of osteoporosis in men. Calcif Tissue Int 75(2):114–119

    Article  PubMed  CAS  Google Scholar 

  10. Thompson DD, Simmons HA, Pirie CM, Ke HZ (1995) FDA Guidelines and animal models for osteoporosis. Bone 17(4 Suppl):125S–133S

    PubMed  CAS  Google Scholar 

  11. Wink CS, Felts WJ (1980) Effects of castration on the bone structure of male rats: a model of osteoporosis. Calcif Tissue Int 32(1):77–82

    Article  PubMed  CAS  Google Scholar 

  12. Verhas M, Schoutens A, L’hermite-Baleriaux M, Dourov N, Verschaeren A, Mone M, Heilporn A (1986) The effect of orchidectomy on bone metabolism in aging rats. Calcif Tissue Int 39(2):74–77

    Article  PubMed  CAS  Google Scholar 

  13. Moreau MF, Libouban H, Legrand E, Baslé MF, Audran M, Chappard D (2001) Lean, fat and bone masses are influenced by orchidectomy in the rat. A densitometric X-ray absorptiometric study. J Musculoskel Neuron Interact 1(3):209–213

    CAS  Google Scholar 

  14. Erben RG, Eberle J, Stahr K, Goldberg M (2000) Androgen deficiency induces high turnover osteopenia in aged male rats: a sequential histomorphometric study. J Bone Miner Res 15(6):1085–1098

    Article  PubMed  CAS  Google Scholar 

  15. Jee WS, Ma Y (1999) Animal models of immobilization osteopenia. Morphologie 83(261):25–34

    PubMed  CAS  Google Scholar 

  16. Ijiri K, Jee WS, Ma YF, Yuan Z (1995) Remobilization partially restored the bone mass in a non-growing cancellous bone site following long term immobilization. Bone 17(4 Suppl):213S–217S

    PubMed  CAS  Google Scholar 

  17. Yang Li C, Majeska RJ, Laudier DM, Mann R, Schaffler MB (2005) High-dose risedronate treatment partially preserves cancellous bone mass and microarchitecture during long-term disuse. Bone 37(3):287–295

    Article  PubMed  CAS  Google Scholar 

  18. Chappard D, Chennebault A, Moreau M, Legrand E, Audran M, Baslé MF (2001) Texture analysis of X-ray radiographs is a more reliable descriptor of bone loss than mineral content in a rat model of localized disuse induced by the Clostridium botulinum toxin. Bone 28(1):72–79

    Article  PubMed  CAS  Google Scholar 

  19. Hahn M, Vogel M, Pompesius-Kempa M, Delling G (1992) Trabecular bone pattern factor—a new parameter for simple quantification of bone microarchitecture. Bone 13(4):327–330

    Article  PubMed  CAS  Google Scholar 

  20. Jinnai H, Watashiba H, Kajihara T, Nishikawa Y, Takahashi M, Ito M (2002) Surface curvatures of trabecular bone microarchitecture. Bone 30(1):191–194

    Article  PubMed  CAS  Google Scholar 

  21. Chappard D, Alexandre C, Riffat G (1983) Histochemical identification of osteoclasts. Review of current methods and reappraisal of a simple procedure for routine diagnosis on undecalcified human iliac bone biopsies. Basic Appl Histochem 27(2):75–85

    PubMed  CAS  Google Scholar 

  22. Kaija H, Jia J, Lindqvist Y, Andersson G, Vihko P (1999) Tartrate-resistant bone acid phosphatase: large-scale production and purification of the recombinant enzyme, characterization, and crystallization. J Bone Miner Res 14(3):424–430

    Article  PubMed  CAS  Google Scholar 

  23. Waarsing JH, Day JS, van der Linden JC, Ederveen AG, Spanjers C, De Clerck N, Sasov A, Verhaar JA, Weinans H (2004) Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data. Bone 34(1):163–169

    Article  PubMed  CAS  Google Scholar 

  24. Vanderschueren D, Van Herck D, Sinker AMH, Visser WJ, Shot LPC, Bouillon R (1992) Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency. Endocrinology 130(5):2906–2916

    Article  PubMed  CAS  Google Scholar 

  25. Audran M, Chappard D, Legrand E, Libouban H, Basle MF (2001) Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model. Calcif Tissue Int 69(4):214–217

    Article  PubMed  CAS  Google Scholar 

  26. De Souza RL, Matsuura M, Eckstein F, Rawlinson SC, Lanyon LE, Pitsillides AA (2005) Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone 37(6):810–818

    Article  PubMed  Google Scholar 

  27. Warner SE, Sanford DA, Becker BA, Bain SD, Srinivasan S, Gross TS (2006) Botox induced muscle paralysis rapidly degrades bone. Bone 38(2):257–264

    Article  PubMed  CAS  Google Scholar 

  28. Tran Van PT, Vignery A, Baron R (1982) Cellular kinetics of the bone remodeling sequence in the rat. Anat Rec 202(4):445–451

    Article  PubMed  CAS  Google Scholar 

  29. Blouin S, Moreau MF, Weiss P, Daculsi G, Baslé MF, Chappard D (2006) Evaluation of an injectable bone substitute (betaTCP/hydroxyapatite/hydroxy-propyl-methyl-cellulose) in severely osteopenic and aged rats. J Biomed Mater Res 78A:570–580

    Google Scholar 

  30. Okumura H, Yamamuro T, Kasai R, Iwashita Y, Ikeda T (1991) Immobilization combined with ovariectomy and effect of active vitamin D∼3 analogues in the rat. Cells and Materials 1(Suppl 1):125–130

    CAS  Google Scholar 

  31. Lin BY, Jee WS, Chen MM, Ma YF, Ke HZ, Li XJ (1994) Mechanical loading modifies ovariectomy-induced cancellous bone loss. Bone Miner 25(3):199–210

    Article  PubMed  CAS  Google Scholar 

  32. Iwamoto J, Takeda T, Katsumata T, Tanaka T, Ichimura S, Toyama Y (2002) Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats. Bone 30(2):360–367

    Article  PubMed  CAS  Google Scholar 

  33. Iwamoto J, Yeh JK, Takeda T (2003) Effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats. J Bone Miner Res 18(4):776–783

    Article  PubMed  CAS  Google Scholar 

  34. Alatalo SL, Peng Z, Janckila AJ, Kaija H, Vihko P, Vaananen HK, Halleen JM (2003) A novel immunoassay for the determination of tartrate-resistant acid phosphatase 5b from rat serum. J Bone Miner Res 18(1):134–139

    Article  PubMed  CAS  Google Scholar 

  35. Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Vaananen HK (2000) Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 15(7):1337–1345

    Article  PubMed  CAS  Google Scholar 

  36. Halleen JM, Ylipahkala H, Alatalo SL, Janckila AJ, Heikkinen JE, Suominen H, Cheng S, Vaananen HK (2002) Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other markers of bone turnover and bone mineral density. Calcif Tissue Int 71(1):20–25

    Article  PubMed  CAS  Google Scholar 

  37. Surve VV, Andersson N, Alatalo S, Lehto-Axtelius D, Halleen J, Vaananen K, Hakanson R (2001) Does combined gastrectomy and ovariectomy induce greater osteopenia in young female rats than gastrectomy alone? Calcif Tissue Int 69(5):274–280

    Article  PubMed  CAS  Google Scholar 

  38. Erben RG, Eberle J, Stahr K, Goldberg M (2000) Androgen deficiency induces high turnover osteopenia in aged male rats: a sequential histomorphometric study. J Bone Miner Res 15(6):1085–1098

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are greatly indebted to P. Legras and J. Leroux for their help with the animal care and to G. Brossard and N. Gaborit for their help with the X-ray microCT. This work was supported by funds from “Pays de la Loire”–Axe Biomatériaux and INSERM.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Chappard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blouin, S., Gallois, Y., Moreau, M.F. et al. Disuse and orchidectomy have additional effects on bone loss in the aged male rat. Osteoporos Int 18, 85–92 (2007). https://doi.org/10.1007/s00198-006-0197-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-006-0197-8

Keywords

Navigation