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The effects of systemic chemical sympathectomy on local bone loss induced by sciatic neurectomy

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

It has been suggested that the sympathetic nervous system (SNS) is involved in bone metabolism and that blockade of the SNS could reduce bone loss and stimulate bone formation. However, the question of whether suppression of SNS tone could compensate for mechanical unloading-induced bone loss must be further clarified. The purpose of this study was to investigate whether systemically inhibiting sympathetic nervous system (SNS) tone could prevent bone loss from mechanical-inactivity-induced osteopenia.

Methods

Female Wistar rats (12 weeks old) were randomly assigned to three groups: the SN group (n = 10), or single leg sciatic neurectomy group; the SNP group (n = 12), or single leg sciatic neurectomy + propranolol treatment (0.5 g/L in dietary water) group; and the CON group (n = 10), or single leg sham-operated group. Animals were fed with distilled water or propranolol in water, in accordance with their group design, for 30 days. Histomorphometry, geometry, tissue weight, and serum markers were assessed.

Results

Propranolol-treated animals drank significantly less water, but did not differ in daily chow consumption or body weight gain. In histomorphometric analysis, the spongy bone volume ratio in proximal tibiae was significantly lower in the two sciatic neurectomy groups, but there was no difference between the SN and SNP groups. Architecture analysis showed that the SN group had significantly thinner trabeculae and fewer trabeculae than the CON group (p < 0.05), but there was no difference between the SNP and CON groups. There were no significant differences for tissue weight, geometric measurement, or serum markers assay.

Conclusion

It was observed that blockade of the SNS prevented neurectomy-induced bone resorption, as demonstrated by various histomorphometric data, although the difference between SN and SNP did not reach significance. In further work it would be valuable to study possible gender, age, and dose-dependent efficacy of propranolol on bone metabolism.

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References

  1. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111:305–17.

    Article  PubMed  CAS  Google Scholar 

  2. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005;434:514–20.

    Article  PubMed  CAS  Google Scholar 

  3. Bonnet N, Benhamou CL, Malaval L, Goncalves C, Vico L, Eder V, Pichon C, Courteix D. Low dose beta-blocker prevents ovariectomy-induced bone loss in rats without affecting heart functions. J Cell Physiol. 2008;217:819–27.

    Article  PubMed  CAS  Google Scholar 

  4. Bonnet N, Laroche N, Vico L, Dolleans E, Benhamou CL, Courteix D. Dose effects of propranolol on cancellous and cortical bone in ovariectomized adult rats. J Pharmacol Exp Ther. 2006;318:1118–27.

    Article  PubMed  CAS  Google Scholar 

  5. Pasco JA, Henry MJ, Sanders KM, Kotowicz MA, Seeman E, Nicholson GC. Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. J Bone Miner Res. 2004;19:19–24.

    Article  PubMed  CAS  Google Scholar 

  6. Jessop HL, Suswillo RF, Rawlinson SC, Zaman G, Lee K, Das-Gupta V, Pitsillides AA, Lanyon LE. Osteoblast-like cells from estrogen receptor alpha knockout mice have deficient responses to mechanical strain. J Bone Miner Res. 2004;19:938–46.

    Article  PubMed  CAS  Google Scholar 

  7. Jagger CJ, Chow JW, Chambers TJ. Estrogen suppresses activation but enhances formation phase of osteogenic response to mechanical stimulation in rat bone. J Clin Invest. 1996;98:2351–7.

    Article  PubMed  CAS  Google Scholar 

  8. Westerlind KC, Wronski TJ, Ritman EL, Luo ZP, An KN, Bell NH, Turner RT. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. Proc Natl Acad Sci USA. 1997;94:4199–204.

    Article  PubMed  CAS  Google Scholar 

  9. Levasseur R, Sabatier JP, Potrel-Burgot C, Lecoq B, Creveuil C, Marcelli C. Sympathetic nervous system as transmitter of mechanical loading in bone. Joint Bone Spine. 2003;70:515–9.

    Article  Google Scholar 

  10. Kondo H, Nifuji A, Takeda S, Ezura Y, Rittling SR, Denhardt DT, Nakashima K, Karsenty G, Noda M. Unloading induces osteoblastic cell suppression and osteoclastic cell activation to lead to bone loss via sympathetic nervous system. J Biol Chem. 2005;280:30192–200.

    Article  PubMed  CAS  Google Scholar 

  11. de Souza RL, Pitsillides AA, Lanyon LE, Skerry TM, Chenu C. Sympathetic nervous system does not mediate the load-induced cortical new bone formation. J Bone Miner Res. 2005;20:2159–68.

    Article  PubMed  Google Scholar 

  12. Marenzana M, De Souza RL, Chenu C. Blockade of beta-adrenergic signaling does not influence the bone mechano-adaptive response in mice. Bone. 2007;41:206–15.

    Article  PubMed  CAS  Google Scholar 

  13. Moffitt JA, Grippo AJ, Beltz TG, Johnson AK. Hindlimb unloading elicits anhedonia and sympathovagal imbalance. J Appl Physiol. 2008;105:1049–59.

    Article  PubMed  Google Scholar 

  14. Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, Trembovler V, Csernus V, Shohami E, Bab I. Depression induces bone loss through stimulation of the sympathetic nervous system. Proc Natl Acad Sci USA. 2006;103:16876–81.

    Article  PubMed  CAS  Google Scholar 

  15. Uchida S, Doi Y, Kudo H, Furukawa H, Nakamura T, Fujimoto S. Transient expression of activin betaA mRNA on osteoprogenitor cells in rat bone regeneration after drill-hole injury. Bone. 2000;27:81–90.

    Article  PubMed  CAS  Google Scholar 

  16. FDA. INDERIDE® [propranolol hydrochloride (Inderal®) and hydrochlorothiazide) (database on the Internet) 2008. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018031s035lbl.pdf.

  17. Roxane Laboratories, Inc. Propranolol oral solution description (database on the Internet) 2008. Available from: http://www.drugs.com/pro/propranolol-oral-solution.html.

  18. Kishi Y, Kurosawa H, Endo S. Is propranolol effective in primary polydipsia? Int J Psychiatry Med. 1998;28:315–25.

    Article  PubMed  CAS  Google Scholar 

  19. Kirby RF, Novak CM, Thunhorst RL, Johnson AK. The role of beta1 and beta2 adrenoceptors in isoproterenol-induced drinking. Brain Res. 1994;656:79–84.

    Article  PubMed  CAS  Google Scholar 

  20. Weinreb M, Rodan GA, Thompson DD. Osteopenia in the immobilized rat hind limb is associated with increased bone resorption and decreased bone formation. Bone. 1989;10:187–94.

    Article  PubMed  CAS  Google Scholar 

  21. Frost HM. Bone’s mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol. 2003;275A:1081–101.

    Article  Google Scholar 

  22. Serre CM, Farlay D, Delmas PD, Chenu C. Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers. Bone. 1999;25:623–9.

    Article  PubMed  CAS  Google Scholar 

  23. Leppanen OV, Sievanen H, Jokihaara J, Pajamaki I, Kannus P, Cooper DM, Jarvinen TL. The effects of loading and estrogen on rat bone growth. J Appl Physiol. 2010;108:1737–44.

    Article  PubMed  CAS  Google Scholar 

  24. Jiang SD, Jiang LS, Dai LY. Spinal cord injury causes more damage to bone mass, bone structure, biomechanical properties and bone metabolism than sciatic neurectomy in young rats. Osteoporos Int. 2006;17:1552–61.

    Article  PubMed  Google Scholar 

  25. Khosla S, Bilezikian JP. The role of estrogens in men and androgens in women. Endocrinol Metab Clin North Am. 2003;32:195–218.

    Article  PubMed  CAS  Google Scholar 

  26. Pierroz DD, Bouxsein ML, Rizzoli R, Ferrari SL. Combined treatment with a beta-blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized mice. Bone. 2006;39:260–7.

    Article  PubMed  CAS  Google Scholar 

  27. Zhang W, Kanehara M, Zhang Y, Wang X, Ishida T. Beta-blocker and other analogous treatments that affect bone mass and sympathetic nerve activity in ovariectomized rats. Am J Chin Med. 2007;35:89–101.

    Article  PubMed  Google Scholar 

  28. Sato T, Arai M, Goto S, Togari A. Effects of propranolol on bone metabolism in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2010;334:99–105.

    Article  PubMed  CAS  Google Scholar 

  29. Pierroz DD, Bouxsein ML, Muzzin P, Rizzoli R, Ferrari SL. Bone loss following ovariectomy is maintained in absence of adrenergic receptor β1 and β2 signaling. J Bone Miner Res. 2005;20:s277.

    Google Scholar 

  30. Pierroz DD, Baldock PA, Bouxsein ML, Ferrari SL. Low cortical bone mass in mice lacking beta 1 and beta 2 adrenergic receptors is associated with low bone formation and circulating IGF-1. J Bone Miner Res. 2006;21:s277.

    Google Scholar 

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Acknowledgments

This study was supported by the National Science Council of Taiwan (NSC 95-2413-H-006-011-MY2). Editorial assistance in English by Miss Jae Cody is appreciated.

Conflict of interest

None of the authors has any conflicts of interest.

Author information

Authors and Affiliations

  1. Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan, Taiwan

    Tsang-Hai Huang

  2. Department of Physical Education, National Taiwan Normal University, Taipei, Taiwan

    Hsin-Shih Lin

  3. Department of Physiology, National Cheng Kung University, Tainan, Taiwan

    Hsiun-Ing Chen

  4. National Taiwan University Hospital, Taipei, Taiwan

    Rong-Sen Yang

  5. Department of Orthopaedics, National Taiwan University and Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan

    Rong-Sen Yang

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  1. Tsang-Hai Huang
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  2. Hsin-Shih Lin
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Correspondence to Rong-Sen Yang.

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Huang, TH., Lin, HS., Chen, HI. et al. The effects of systemic chemical sympathectomy on local bone loss induced by sciatic neurectomy. J Orthop Sci 16, 629–637 (2011). https://doi.org/10.1007/s00776-011-0117-4

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  • DOI: https://doi.org/10.1007/s00776-011-0117-4

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