The Effect of the Vestibular System on Bone Regeneration: a Look at the Vestibular ‎System Beyond its Classical Role

Document Type : Review Article

Authors

Department of Audiology, Faculty of Rehabilitation, University of Rehabilitation Sciences ‎and Social welfare, Tehran, Iran

Abstract

Purpose:
The purpose of this study is to investigate the effect of the vestibular system on the bone formation process and the possible path of this effect. Also, in the present study, an attempt has been made to provide evidence related to this effect and its importance in clinical work.
Methods:
For this review article, the keywords "bilateral vestibulopathy", "bone regeneration", "sympathetic vestibular reflex" and "sympathetic nervous system" were searched from 1980 to 2022 in the "google scholar" and "pub Med" databases.
Results:
After searching the mentioned sources of information, a total of 13 articles were obtained. Among these articles, 8 were research articles (animal and human studies). Therefore, the results of these 7 articles were used for discussion and conclusions
Conclusion:
Recent studies have stated that the vestibular system may play a role in the bone regeneration process through the effect on the sympathetic system. The vestibular system is a small part of the auditory system located in the inner ear in the temporal bone. The vestibular system has many connections with important centers in the brain stem. On the other hand, the sympathetic nervous system also acts as an intermediary mechanism through which the central nervous system exerts its effects. The presence of these extensive and complex connections, which are both upward and downward, justifies the influence of the vestibular system on bone regeneration.

Keywords


  1. Zaidi M. Skeletal remodeling in health and disease. Nat Med 2007; 13(7): 791-801.
  2. Sims NA, Gooi JH. Bone remodeling: Multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol 2008; 19(5): 444-451.
  3. Novack DV, Teitelbaum SL. The osteoclast: friend or foe? Annu Rev Pathol 2008; 3(1): 457-484.
  4. Karsenty G, Kronenberg HM, Settembre C. Genetic control of bone formation. Annu Rev Cell Dev Biol 2009; 25(1): 629-648.
  5. Mano T, Nishimura N, Iwase S. Sympathetic neural influence on bone metabolism in microgravity. Acta Physiol Hung 2010; 97(4): 354-361.
  6. Prevention O. Diagnosis, and therapy. NIH consens statement 2000; 17(1): 1-36.
  7. Greenspan SL, Myers ER, Maitland LA, Resnick NM, Hayes WC. Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly. JAMA 1994; 271(2): 128-133.
  8. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312(7041): 1254-1259.
  9. Ducy P, Amling M, Takeda S, Priemel M, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000; 100(2): 197-207.
  10. Perkins MN, Rothwell NJ, Stock MJ, Stone TW. Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 1981; 289(5796): 401-402.
  11. Satoh N, Ogawa Y, Katsuura G, Numata Y, et al. Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion. Diabetes 1999; 48(9): 1787-1793.
  12. Yadav VK, Oury F, Suda N, Liu Z-W, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 2009; 138(5): 976-989.
  13. Togari A, Arai M, Mizutani S, Mizutani S, et al. Expression of mRNAs for neuropeptide receptors and β-adrenergic receptors in human osteoblasts and human osteogenic sarcoma cells. Neurosci Lett 1997; 233(2-3): 125-128.
  14. Kellenberger S, Muller K, Richener H, Bilbe G. Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like cells by activating β2-adrenergic receptors. Bone 1998; 22(5): 471-478.
  15. Elefteriou F, Ahn JD, Takeda S, Starbuck M, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005; 434(7032): 514-520.
  16. Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell 2005; 122(5): 803-815.
  17. Elefteriou F. Impact of the autonomic nervous system on the skeleton. Physiol Rev 2018; 98(3): 1083-1120.
  18. Carter JR, Ray CA. Sympathetic responses to vestibular activation in humans. Am J Physiol Regul Integr Comp Physiol 2008; 294(3): 681-688.
  19. Kerman I, Yates B. Regional and functional differences in the distribution of vestibulosympathetic reflexes. Am J Physiol 1998; 275(3): R824-R835.
  20. Kasumacic N, Glover JC, Perreault MC. Vestibular- mediated synaptic inputs and pathways to sympathetic preganglionic neurons in the neonatal mouse. J Physiol 2012; 590(22): 5809-5826.
  21. Mori RL, Cotter LA, Arendt HE, Olsheski CJ, Yates BJ. Effects of bilateral vestibular nucleus lesions on cardiovascular regulation in conscious cats. J Appl Physiol 2005; 98(2): 526-533.
  22. Mendy A, Vieira ER, Albatineh AN, Nnadi AK, et al. Low bone mineral density is associated with balance and hearing impairments. Ann Epidemiol 2014; 24(1): 58-62.
  23. Radaei F, Gharibzadeh S. Relationship between bone mineral density and balance disorders in osteoporotic patients. Front Bioeng Biotechnol 2013; 19(1):5.
  24. Bigelow RT, Semenov YR, Anson E, Du Lac S, et al. Impaired vestibular function and low bone mineral density: data from the baltimore longitudinal study of aging. J Assoc Res Otolaryngol 2016; 17(5): 433-440.
  25. Kahveci O, Demirdal U, Yücedag F, Cerci U. Patients with osteoporosis have higher incidence of sensorineural hearing loss. Clin Otolaryngol 2014; 39(3): 145-149.
  26. Park RJ, Kim YH. Association between osteoporosis/osteopenia and vestibular dysfunction in South Korean adults. Ear Hear 2016; 37(5): 615-619.
  27. Hitier M, Hamon M, Denise P, Lacoudre J, et al. Lateral semicircular canal asymmetry in idiopathic scoliosis: an early link between biomechanical, hormonal and neurosensory theories? PLoS One 2015; 10(7): 131-120.
  28. Jeong SH, Choi SH, Kim JY, Koo HJ, Km JS. Osteopenia and osteoporosis in idiopathic benign positional vertigo. Neurology 2009; 72(12):1069-1076.
  29. Parham K, Leonard G, Feinn RS, Lafreniere D, Kenny AM. Prospective clinical investigation of the relationship between idiopathic benign paroxysmal positional vertigo and bone turnover: a pilot study. Laryngoscope 2013; 123(11): 2834-2839.
  30. Shupak A, Faranesh N. Bone Mineral Density in Patients Suffering from Meniere’s Disease. Audiol Neurootol 2020; 25(3): 158-163.
  31. Choi HG, Chung J, Yoo DM, Lee CH, Kim SY. Association between Osteoporosis and Meniere’s Disease: Two Longitudinal Follow-Up Cohort Studies. Nutrients 2022; 14(22): 48-85.
  32. Vignaux G, Ndong JD, Perrien DS, Elefteriou F. Inner ear vestibular signals regulate bone remodeling via the sympathetic nervous system. J Bone Miner Res 2015; 30(6): 1103-1111.
  33. Levasseur R, Sabatier JP, Etard O, Denise P, Reber A. Labyrinthectomy decreases bone mineral density in the femoral metaphysis in rats. J Vestib Res 2004; 14(5): 361-365.
  34. Vignaux G, Besnard S, Ndong J, Philoxène B, et al. Bone remodeling is regulated by inner ear vestibular signals. J Bone Miner Res 2013; 28(10): 2136-2144.
  35. Shaabani M, Lotfi Y, Karimian SM, Rahgozar M, Hooshmandi M. Short-term galvanic vestibular stimulation promotes functional recovery and neurogenesis in unilaterally labyrinthectomized rats. Brain Res 2016; 1648(1): 152-162.
  36. Shaabani M, Lotfi Y, Karimian SM, Rahgozar M, Hooshmandi M. Data on galvanic-evoked head movements in healthy and unilaterally labyrinthectomized rats. Data Brief 2016; 9(1): 338-344.
  37. Ossenkopp K-P, Prkacin A, Hargreaves EL. Sodium arsenilate-induced vestibular dysfunction in rats: effects on open-field behavior and spontaneous activity in the automated digiscan monitoring system. Pharmacol Biochem Behav 1990; 36(4): 875-881.
  38. Kawao N, Morita H, Obata K, Tamura Y, et al. The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice. Physiol Rep 2016; 4(19): 129-179.
  39. Cherruau M, Facchinetti P, Baroukh B, Saffar J. Chemical sympathectomy impairs bone resorption in rats: a role for the sympathetic system on bone metabolism. Bone 1999; 25(5): 545-451.
  40. Barmack NH. Central vestibular system: vestibular nuclei and posterior cerebellum. Brain Res Bull 2003; 60(5-6): 511-541.
  41. Yates BJ. The vestibular system and cardiovascular responses to altered gravity. Am J Physiol Regul Integr Comp Physiol 2004; 286(1): 22-30.
  42. Etard O, Reber A, Quarck G, Normand H, et al. Vestibular control on blood pressure during parabolic flights in awake rats. Neuroreport 2004; 15(15): 2357-2360.
  43. Abe C, Tanaka K, Awazu C, Morita H. Strong galvanic vestibular stimulation obscures arterial pressure response to gravitational change in conscious rats. J Appl Physiol 2008; 104(1): 34-40.
  44. Lotfi Y, Mardani N, Rezazade N, Saeidi KE, Bakhshi E. Vestibular function in patients with vestibular migraine. Aud Vest Res 2016; 25(3): 166-174.
  45. Hammam E, Macefield VG. Vestibular modulation of sympathetic nerve activity to muscle and skin in humans. Front Neurol 2017; 8(1): 334.
  46. Pliego A, Vega R, Gómez R, Reyes-Lagos JJ, Soto E. A transient decrease in heart rate with unilateral and bilateral galvanic vestibular stimulation in healthy humans. Eur J Neurosci 2021; 54(2): 4670-4681.
  47. Fulwiler CE, Saper CB. Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat. Brain Res 1984; 7(3): 229-259.
  48. Nagai M, Scheper V, Lenarz T, Förster CY. The insular cortex as a vestibular area in relation to autonomic function. Clin Auton Res 2021; 31(1): 179-85.
  49. 49. Yates BJ, Bolton PS, Macefield VG. Vestibulo-sympathetic responses. Compr Physiol 2014; 4(2): 851-887.