Adrenergic control of bone remodeling and its implications for the treatment of osteoporosis

Journal of Musculoskeletal Neuronal Interactions

Volumn 8, Issue 2, 2008, Pages 94-104

  Bonnet, N ^a   Pierroz, D D ^a   Ferrari, Serge L ^a  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Adrenergic signaling; Animal and human studies; Bone remodeling; Osteoblast; Osteoclast

Indexed keywords

ADRENERGIC RECEPTOR BLOCKING AGENT; ADRENERGIC RECEPTOR STIMULATING AGENT; BETA 1 ADRENERGIC RECEPTOR; BETA 1 ADRENERGIC RECEPTOR BLOCKING AGENT; BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CLENBUTEROL; CORTICOSTEROID; FORMOTEROL; GLUCOCORTICOID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISOPRENALINE; PARATHYROID HORMONE; PLACEBO; PROPRANOLOL; SALBUTAMOL; THIAZIDE DIURETIC AGENT;

ADRENERGIC STIMULATION; ADRENERGIC SYSTEM; ASTHMA; BIOMECHANICS; BONE DENSITY; BONE MASS; BONE METABOLISM; BONE REMODELING; BONE STRENGTH; BONE STRUCTURE; BONE TURNOVER; CLINICAL TRIAL; CYTOKINE PRODUCTION; DOSE RESPONSE; DRUG INTERMITTENT THERAPY; DRUG POTENTIATION; FRACTURE; HUMAN; LOW DRUG DOSE; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; RECEPTOR DOWN REGULATION; REVIEW;

ADRENERGIC AGENTS; ADRENERGIC AGONISTS; ADRENERGIC ANTAGONISTS; ANIMALS; BONE AND BONES; BONE REMODELING; BONE RESORPTION; HUMANS; OSTEOCLASTS; OSTEOPOROSIS; PARATHYROID HORMONE; RECEPTORS, ADRENERGIC; RECEPTORS, ADRENERGIC, BETA-1; RECEPTORS, ADRENERGIC, BETA-2; SIGNAL TRANSDUCTION;

EID: 51749102413     PISSN: 11087161     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (77)

1. Seeman E, Delmas PD. Bone quality - the material and structural basis of bone strength and fragility. N Engl J Med 2006;354:2250-61.
2. Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002;359:1841-50.
3. 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.
4. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker K. L, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002;111:305-17.
5. Karsenty G. Leptin controls bone formation through a hypothalamic relay. Recent Prog Horm Res 2001;56:401-15.
6. 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.
7. Togari A, Arai M, Mizutani S, Mizutani S, Koshihara Y, Nagatsu T. Expression of mRNAs for neuropeptide receptors and beta-adrenergic receptors in human osteoblasts and human osteogenic sarcoma cells. Neurosci Lett 1997;233:125-8.
8. Togari A. Adrenergic regulation of bone metabolism: possible involvement of sympathetic innervation of osteoblastic and osteoclastic cells. Microsc Res Tech 2002;58:77-84.
9. Kellenberger S, Muller K, Richener H, Bilbe G. Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like cells by activating beta2-adrenergic receptors. Bone 1998;22:471-8.
10. Moore RE, Smith CK, Bailey CS, Voelkel EF, Tashjian AH Jr. Characterization of beta-adrenergic receptors on rat and human osteoblast-like cells and demonstration that beta-receptor agonists can stimulate bone resorption in organ culture. Bone Miner 1993;23:301-15.
11. 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; In revision.
12. Pierroz DD, Baldock P, 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(Suppl.1):S277.
13. Suzuki A, Palmer G, Bonjour JP, Caverzasio J. Catecholamines stimulate the proliferation and alkaline phosphatase activity of MC3T3-E1 osteoblast-like cells. Bone 1998;23:197-203.
14. Suzuki A, Palmer G, Bonjour JP, Caverzasio J. Regulation of alkaline phosphatase activity by p38 MAP kinase in response to activation of Gi protein-coupled receptors by epinephrine in osteoblast-like cells. Endocrinology 1999;140:3177-82.
15. Majeska RJ, Minkowitz B, Bastian W, Einhorn TA. Effects of beta-adrenergic blockade in an osteoblast-like cell line. J Orthop Res 1992;10:379-84.
16. Owen TA, Bortell R, Yocum SA, Smock SL, Zhang M, Abate C, Shalhoub V, Aronin N, Wright KL, van Wijnen AJ. Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Proc Natl Acad Sci USA 1990;87:9990-4.
17. Elefteriou F. Neuronal signaling and the regulation of bone remodeling. Cell Mol Life Sci 2005;62:2339-49.
18. Minkowitz B, Boskey AL, Lane JM, Pearlman HS, Vigorita VJ. Effects of propranolol on bone metabolism in the rat. J Orthop Res 1991;9:869-75.
19. 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.
20. 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.
21. Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, Trembovler V, Csernus V, Shohami E, Bab I. From the cover: depression induces bone loss through stimulation of the sympathetic nervous system. Proc Natl Acad Sci USA 2006;103:16876-81.
22. Hamrick MW, Ferrari SL. Leptin and the sympathetic connection of fat to bone. Osteoporos Int 2007;19:905-12.
23. Elenkov IJ. Wilder RL. Chrousos GP, Vizi ES. The sympathetic nerve - an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000;52:595-638.
24. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42.
25. Teitelbaum SL. Osteoclasts: what do they do and how do they do it? Am J Pathol 2007;170:427-35.
26. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-76.
27. Takeuchi T, Tsuboi T, Arai M, Togari A. Adrenergic stimulation of osteoclastogenesis mediated by expression of osteoclast differentiation factor in MC3T3-E1 osteoblast-like cells. Biochem Pharmacol 2001;61:579-86.
28. Kondo A, Togari A. In vivo stimulation of sympathetic nervous system modulates osteoblastic activity in mouse calvaria. Am J Physiol Endocrinol Metab 2003;285:E661-7.
29. Arai M, Nagasawa T, Koshihara Y, Yamamoto S, Togari A. Effects of beta-adrenergic agonists on bone-resorbing activity in human osteoclast-like cells. Biochem Biophys Acta 2003;1640:137-42.
30. Frediani U, Becherini L, Lasagni L, Tanini A, Brandi ML. Catecholamines modulate growth and differentiation of human preosteoclastic cells. Osteoporos Int 1996;6:14-21.
31. Bonnet N, Brunet-Imbault B, Arlettaz A, Horcajada M.N, Collomp K, Benhamou C.L, Courteix D. Alteration of trabecular bone under chronic beta 2 agonists treatment. Med Sci Sports Exerc 2005;37:1493-501.
32. Cavalie H, Lac G, Lebecque P, Chanteranne B, Davicco MJ, Barlet JP. Influence of clenbuterol on bone metabolism in exercised or sedentary rats. J Appl Physiol 2002;93:2034-7.
33. Bonnet N, Benhamou CL, Brunet-Imbault B, Arlettaz A, Horcajada MN, Richard O, Vico L, Collomp K, Courteix D. Severe bone alterations under beta 2 agonist treatment: bone mass, microarchitecture and strength analyses in female rats. Bone 2005;37:622-33.
34. Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 2005;20:994-1001.
35. Hamrick MW, Pennington C, Newton D, Xie D, Isales C. Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone 2004;34:376-83.
36. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002;3:639-50.
37. Rey A, Manen D, Rizzoli R, Caverzasio J, Ferrari SL. Proline-rich motifs in the parathyroid hormone (PTH)/PTH-related protein receptor C terminus mediate scaffolding of c-Src with beta-arrestin2 for ERK1/2 activation. J Biol Chem 2006;281:38181-8.
38. Pierce KL, Maudsley S, Daaka Y, Luttrell LM, Lefkowitz RJ. Role of endocytosis in the activation of the extracellular signal-regulated kinase cascade by sequestering and nonsequestering G protein-coupled receptors. Proc Natl Acad Sci USA 2000;97:1489-94.
39. Wisler JW, DeWire SM, Whalen EJ, Violin JD, Drake MT, Ahn S, Shenoy SK, Lefkowitz RJ. A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci USA 2007;104:16657-62
40. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, Hanauer A, Karsenty G. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell 2004;117:387-98.
41. Goltzman D. Interactions of PTH and PTHrP with the PTH/PTHrP receptor and with downstream signaling pathways: exceptions that provide the rules. J Bone Miner Res 1999;14:173-7.
42. Chen X, Song IH, Dennis JE, Greenfield EM. Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts. J Bone Miner Res 2007;22:656-64.
43. Kostenuik PJ, Ferrari S, Pierroz D, Bouxsein M, Morony S, Warmington KS, Adamu S, Geng Z, Grisanti M, Shalhoub V, Martin S, Biddlecome G, Shimamoto G, Boone T, Shen V, Lacey D. Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone. J Bone Miner Res 2007;22:1534-47.
44. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000;100:197-207.
45. Suslic VS, Frederich RC, Lawitts J, Tozzo E, Kahn BB, Harper M-E, Himms-Hagen J, Flier JS, Lowell BB. Targeted disruption of the beta3-adrenergic receptor gene. J Biol Chem 1995;270:29483-92.
46. Pierroz DD, Muzzin P, Glatt V, Bouxsein ML, Rizzoli R, Ferrari SL. Beta 1-2-adrenergic receptor KO mice have decreased total body and cortical bone mass despite increased trabecular number. J Bone Miner Res 2004;19(Suppl.1):1121.
47. Pierroz DD, Bouxsein ML, Muzzin P, Rizzoli R, Ferrari SL. Bone loss following ovariectomy is maintained in absence of adrenergic receptor beta1 and beta2 signaling. J Bone Miner Res 2005;20(Suppl.1):S277.
48. Kitaura T, Tsunekawa N, Kraemer WJ. Inhibited longitudinal growth of bones in young male rats by clenbuterol. Med Sci Sports Exerc 2002;34:267-73.
49. Pataki A, Muller K, Bilbe G, Green JR, Glatt M. Anabolic effects of beta2-agonists, formoterol and salbutamol on cancellous bone ovariectomized (ovx) rat. Bone 1996;9:A116.
50. Frost HM, Schönau E. The "muscle-bone unit" in children and adolescents: a 2000 overview. J Pediatr Endocrinol Metab 2000; 13:571-90.
51. Zeman RJ, Hirschman A, Hirschman ML, Guo G, Etlinger JD. Clenbuterol, a beta 2-receptor agonist, reduces net bone loss in denervated hindlimbs. Am J Physiol 1991;261:E285-9.
52. Bonnet N, Laroche N, Beaupied H, Vico L, Dolleans E, Benhamou CL, Courteix D. Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats. J Appl Physiol 2007;103:524-33.
53. Apseloff G, Girten B, Walker M, Shepard DR, Krecic ME, Stern LS, Gerber N. Aminohydroxybutane bisphosphonate and clenbuterol prevent bone changes and retard muscle atrophy respectively in tail-suspended rats. J Pharmacol Exp Ther 1993;264:1071-8.
54. Levasseur R, Sabatier J, Potrel-Burgot C, Lecoq B, Creveuil C, Marcelli C. Sympathetic nervous system as transmitter of mechanical loading in bone. Joint Bone Spine 2003;70:515-59.
55. Kondo H, Nifuji A, Takeda S, Ezura Y, Rittling S, 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.
56. 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.
57. 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.
58. Warden SJ, Bliziotes MM, Wiren KM, Eshleman AJ, Turner CH. Neural regulation of bone and the skeletal effects of serotonin (5-hydroxytryptamine). Mol Cell Endocrinol 2005;242:1-9.
59. Warden SJ, Robling AG, Sanders MS, Bliziotes MM, Turner CH. Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology 2005;146:685-93.
60. Yaoita H, Sakabe A, Maehara K, Maruyama Y. Different effects of carvedilol, metoprolol, and propranolol on left ventricular remodeling after coronary stenosis or after permanent coronary occlusion in rats. Circulation 2002;105:975-80.
61. Bonnet N. Beta agonistes et antagonistes, exercice physique et tissu osseux: modifications architecturales, densitométriques, biomécaniques et métaboliques de l'os chez la rate ovariectomisée ou non. Thèse Biologie - Santé université Orléans, 2006.
62. 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.
63. De Vries F, Pouwels S, Bracke M, Leufkens HG, Cooper C, Lammers JW, van Staa TP. Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf 2007;16:612-29.
64. Schwartzman RJ. New treatments for reflex sympathetic dystrophy. N Engl J Med 2000;343:1811-2.
65. Collomp K, Le Panse B, Portier H, Lecoq AM, Jaffre C, Beaupied H, Richard O, Benhamou L, Courteix D, De Ceaurriz J. Effects of acute salbutamol intake during a Wingate test. Int J Sports Med 2005;26:513-7.
66. 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.
67. Schlienger RG, Kraenzlin ME, Jick SS, Meier CR. Use of beta-blockers and risk of fractures. JAMA 2004;292:1326-32.
68. Rejnmark L, Vestergaard P, Kassem M, Christoffersen BR, Kolthoff N, Brixen K, Mosekilde L. Fracture risk in perimenopausal women treated with beta-blockers. Calcif Tissue Int 2004;75:365-72.
69. Rejnmark L, Vestergaard P, Mosekilde L. Treatment with beta-blockers. ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens 2006;24:581-9.
70. Reid IR, Gamble GD, Grey AB, Black DM, Ensrud KE, Browner WS, Bauer DC. beta-blocker use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Res 2005;20:613-8.
71. Reid IR, Lucas J, Wattie D, Horne A, Bolland M, Gamble GD, Davidson JS, Grey AB. Effects of a beta-blocker on bone turnover in normal postmenopausal women: a randomized controlled trial. J Clin Endocrinol Metab 2005;90:5212-6.
72. Pasco JA, Henry MJ, Nicholson GC, Schneider HG, Kotowicz MA. Beta-blockers reduce bone resorption marker in early postmenopausal women. Ann Hum Biol 2005;32:738-45.
73. Bonnet N, Gadois C, McCloskey E, Lemineur G, Lespessailles E, Courteix D, Benhamou CL. Protective effect of beta blockers in postmenopausal women: Influence on fractures, bone density, micro and macroarchitecture. Bone 2007;40:1209-16.
74. Wiens M, Etminan M, Gill SS, Takkouche B. Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med 2006;260:350-62.
75. Levasseur R, Dargent-Molina P, Sabatier JP, Marcelli C, Breart G. Beta-blocker use, bone mineral density, and fracture risk in older women: results from the Epidemiologie de l'Osteoporose prospective study. J Am Geriatr Soc 2005;53:550-2.
76. De Vries F, Souverein PC, Cooper C, Leufkens HG, van Staa TP. Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and The Netherlands. Calcif Tissue Int 2007;80:69-75.
77. Turker S, Karatosun V, Gunal I. Beta-blockers increase bone mineral density. Clin Orthop Relat Res 2006; 443:73-4.