Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Smitham, P.; Goodship, A.; Blunn, G.; Crossfield, L.; Hughes, G.; Chenu, C. (2014)
Publisher: BlackWell Publishing Ltd
Journal: Journal of Orthopaedic Research
Types: Article
Subjects: propranolol; bone architecture; fracture healing; micro-CT; mechanical testing;, Research Article, bone architecture, propranolol, micro-CT, fracture healing, mechanical testing
Experimental studies suggest that the β-blocker propranolol stimulates bone formation but little work has investigated its effect on fracture healing. In this study, we examined if a low dose of propranolol, previously shown to be preventive against bone loss in rats, improves bone repair. Female Wistar rats were injected with saline or propranolol (0.1-mg/kg/day) (n-=-20/group), 5 days a week for 8 weeks. Three weeks after the beginning of treatment, all rats underwent a mid-diaphyseal transverse osteotomy in the left femur. Radiographic analysis of ostetomy healing was performed 2 and 5 weeks after osteotomy. Rats were sacrificed at 5 weeks and femora collected for measurements of fracture strength by torsional testing, callus volume, and mineral content by micro-CT analysis and histology of fracture callus. Eighty nine percent of osteotomies achieved apparent radiological union by 5 weeks in both groups. Propranolol treatment did not significantly alter the torsional strength of the fractured femur compared with controls. The volume and mineralization of fracture callus at 5 weeks were not significantly different in both groups. Histology showed that endochondral ossification was not affected by propranolol. Altogether, our results demonstrate that propranolol using the regimen described does not significantly improve or inhibit rat osteotomy healing and mechanical strength. © 2014 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Serre CM, Farlay D, Delmas PD, et al. 1999. Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers. Bone 25:623-629.
    • 2. Hara-Irie F, Amizuka N, Ozawa H. 1996. Immunohistochemical and ultrastructural localization of CGRP-positive nerve fibers at the epiphyseal trabecules facing the growth plate of rat femurs. Bone 18:29-39.
    • 3. Hohmann EL, Elde RP, Rysavy JA, et al. 1986. Innervation of periosteum and bone by sympathetic vasoactive intestinal peptide-containing nerve fibers. Science 232:868-871.
    • 4. Mach DB, Rogers SD, Sabino MC, et al. 2002. Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience 113:155-166.
    • 5. Ding Y, Arai M, Kondo H, et al. 2010. Effects of capsaicininduced sensory denervation on bone metabolism in adult rats. Bone 46:1591-1596.
    • 6. Cherruau M, Facchinetti P, Baroukh B, et al. 1999. Chemical sympathectomy impairs bone resorption in rats: a role for the sympathetic system on bone metabolism. Bone 25: 545-551.
    • 7. Elefteriou F. 2008. Regulation of bone remodelling by central and peripheral system. Arch Biochem Biophys 473:231-236.
    • 8. Togari A, Arai M. 2008. Pharmacological topics on bone metabolism: the physiological function of the sympathetic nervous system in modulating bone resorption. J Pharmacol Sci 106:542-546.
    • 9. Takeda S, Karsenty G. 2008. Molecular bases of the sympathetic regulation of bone mass. Bone 42:837-840.
    • 10. Takeda S, Elefteriou F, Levasseur R, et al. 2002. Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305-317.
    • 11. Chenu C, Serre CM, Raynal C, et al. 1998. Glutamate receptors are expressed by bone cells and are involved in bone resorption. Bone 22:295-299.
    • 12. Bliziotes M, Eshleman A, Burt-Pichat B, et al. 2006. Serotonin transporter and receptor expression and function in osteocytic MLO-Y4 cells. Bone 39:1313-1321.
    • 13. Elefteriou F, Ahn JD, Takeda S, et al. 2005. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514-520.
    • 14. Bonnet N, Pierroz DD, Ferrari SL. 2008. Adrenergic control of bone remodelling and its implications for the treatment of osteoporosis. J Musculoskel Neuron Interact 8:94-104.
    • 15. Pierroz DD, Nonnet N, Bianchi EN, et al. Deletion of badrenergic receptor 1,2, or both leads to different bone phenotypes and response to mechanical stimulation. J Bone Miner Res 2012. 27:1252-1262.
    • 16. Kajimura D, Hinoi E, Ferron M, et al. 2011. Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual. J Exp Med 208:841-851.
    • 17. Bonnet N, Laroche N, Vico L, et al. 2006. Dose effects of propranolol on cancellous and cortical bone in ovariectomized adult rats. J Pharmacol Exp Ther 318:1118-1127.
    • 18. Arai M, Sato T, Takeuchi S, et al. 2013. Dose effects of butoxamine, a selective b2-adrenoreceptor antagonist, on bone metabolism in spontaneously hypertensive rat. Eur J Pharmacol 701:7-13.
    • 19. Graham S, Hammond-Jones D, Gamie Z, et al. 2008. The effect of beta-blockers on bone metabolism as potential drugs under investigation for osteoporosis and fracture healing. Expert Opin Investig Drugs 17:1281-1299.
    • 20. Reid IR. 2008. Effects of beta-blockers on fracture risk. J Musculoskelet Neuronal Interact 8:105-110.
    • 21. He J-Y, Jiang L-S, Dai L-Y. 2011. The roles of the sympathetic nervous system in osteoporotic diseases: a review of experimental and clinical studies. Ageing Res Rev 10:253-263.
    • 22. Aro H. 1985. Effect of nerve injury on fracture healing. Callus formation studied in the rat. Acta Othop Scand 56:233-237.
    • 23. Madsen JE, Hukkanen M, Aune AK, et al. 1998. Fracture healing and callus innervation after peripheral nerve resection in rats. Clin Orthop Relat Res 351:230-240.
    • 24. Apel PJ, Crane D, Northam CN, et al. 2009. Effect of selective sensory denervation on fracture healing. J Bone Joint Surg 91:2886-2895.
    • 25. Moran CG, McGrory BJ, Roorda J, et al. 1993. Adrenergic control mechanisms of blood flow in a vascularised canine tibial allograft. J Orthop Res 11:429-437.
    • 26. Long H, Ahmed M, Ackermann P, et al. 2010. Neuropeptide Y innervation during fracture healing and remodelling. A study of angulated tibial fractures in the rat. Acta Orthop 81:639-646.
    • 27. Minkowitz B, Boskey AL, Jane LM, et al. 1991. Effects of propranolol on bone metabolism in the rat. J Orthop Res 9:869-875.
    • 28. Harrison LJ, Cunningham JL, Stromberg L, et al. 2003. Controlled induction of a pseudoarthrosis: a study using a rodent model. J Orthop Trauma 17:11-21.
    • 29. Jeyabalan J, Viollet B, Smitham P, et al. 2013. The antidiabetic drug metformin does not affect bone mass in vivo or fracture healing. Osteoporos Int 24:2659-2670.
    • 30. Chhabra A, Zijerdi D, Zhang J, et al. 2005. BMP-14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J Orthop Trauma 19:629-634.
    • 31. Stro¨mberg L, Dale´n N. 1976. Experimental measurements of maximum torque capacity of long bones. Acta Ortop Scand 47:257-263.
    • 32. Baek K, Bloomfield SA. 2009. Beta-adrenergic blockade and leptin replacement effectively mitigate disuse bone loss. J Bone Miner Res 24:792-799.
    • 33. Marenzana M, De Souza R, Chenu C. 2007. Blockade of badrenergic signalling does not influence the bone mechanoadaptive response in mice. Bone 41:206-215.
    • 34. Rodrigues WF, Madeira MFM, da Silva TA, et al. 2012. Low dose of propranolol down-modulates bone resorption by inhibiting inflammation and osteoclast differentiation. Br J Pharmacol 165:2140-2151.
    • 35. Kondo H, Nifuji A, Takeda S, et al. 2005. Unloading induces osteoblastic cell suppression and osteoclastic cell activation to lead to bone loss via sympathetic nervous system. J Biol Chem 280:30192-33200.
    • 36. Marsell R, Heinhorn TA. 2011. The Biology of fracture healing. Injury 42:551-555.
    • 37. Morgan EF, Mason ZD, Chien KB, et al. 2009. Microcomputed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function. Bone 44:335-344.
    • 38. Aspenberg P. 2005. Drugs and fracture repair. Acta Orthop 76:741-748.
    • 39. Bostrom MP, Yang X, Carson J, et al. 2010. Blockade of beta-adrenergic signalling does not influence fracture healing in a mouse model. J Bone Joint Surg 92-B (Suppl 1):71.
    • 40. Pullar CE, Provost GS, O'Leary AP, et al. 2012. b2AR antagonists and b2AR gene deletion both promote skin wound repair processes. J Invest Dermatol 132:2076-2084.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article