Skip to main content

Advertisement

SpringerLink
Log in

An overview of the etiology of otosclerosis

  • Review Article
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Otosclerosis is the primary disease affecting the homeostasis of otic capsule and is among the most common causes of acquired hearing loss. Otosclerosis is considered as a multifactor disease, caused by both genetic and environmental factors. The aim of the present review is to summarize and analyze the bibliographic data, associated with the etiology of the disease. In some cases, the otosclerosis has an autosomal dominant mode of inheritance with incomplete penetrance. Genetic studies reveal the occurrence of at least nine chromosomal loci as candidate genes of the disease. The localized measles virus infection of the otic capsule has been postulated as a possible etiological theory. The role of hormonal factors, immune and bone-remodeling system in the etiopathogenesis of otosclerosis and the association of the disease with the disorders of the connective tissue are the issues of the present study. Despite the extensive research, many etiological factors and theories have been suggested and the process of development of the otosclerosis remains unclear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Valsalva A (1741) Valsalvae opera et Morgagni epistolae. Venetiis, Italy: Francescus Pitteri:Venetiis. Francescus Pitteri, Italy

    Google Scholar 

  2. Politzer A (1894) Uber primare erkrankung der knockernen labyrinthkapsel. Zeitschrift Fur Ohrenheilkunde 25:309–327

    Google Scholar 

  3. Troltsch Av (1869) Treatise on the diseases of the ear including the anatomy of the organ. William Wood, New York

    Google Scholar 

  4. Siebenman F (1912) Totaler knocherner verschluss beider labyrinthfester und labyrinthitis serosa infolge progessiver spongiosierung. Verhanlungen Deutschen Otologischenn Gesellschaft 6:267–283

    Google Scholar 

  5. Chole RA, McKenna M (2001) Pathophysiology of otosclerosis. Otol Neurotol 22(2):249–257

    Article  PubMed  CAS  Google Scholar 

  6. Iyer PV, Gristwood RE (1984) Histopathology of the stapes in otosclerosis. Pathology 16(1):30–38

    Article  PubMed  CAS  Google Scholar 

  7. Cummings C (1999) Otolaryngology-Head and Neck Surgery. Mosby, pp 535–538

  8. Altmann F, Glasgold A, Macduff JP (1967) The incidence of otosclerosis as related to race and sex. Ann Otol Rhinol Laryngol 76(2):377–392

    PubMed  CAS  Google Scholar 

  9. Morrison AW (1967) Genetic factors in otosclerosis. Ann R Coll Surg Engl 41(2):202–237

    PubMed  CAS  Google Scholar 

  10. Gapany-Gapanavicius B (1975) The incidence of otosclerosis in the general population. Isr J Med Sci 11(5):465–468

    PubMed  CAS  Google Scholar 

  11. Causse JR, Causse JB (1984) Otospongiosis as a genetic disease. Early detection, medical management, and prevention. Am J Otol 5(3):211–223

    PubMed  CAS  Google Scholar 

  12. Levin G, Fabian P, Stahle J (1988) Incidence of otosclerosis. Am J Otol 9(4):299–301

    PubMed  CAS  Google Scholar 

  13. Cajade Frias J, Labella Caballero T (2003) Epidemiological aspects of otosclerosis (1). Its frequency in comparison with other ear pathologies, incidence and prevalence. An Otorrinolaringol Ibero Am 30(1):1–15

    PubMed  CAS  Google Scholar 

  14. Joseph RB, Frazer JP (1964) Otosclerosis Incidence in Caucasians and Japanese. Arch Otolaryngol 80:256–262

    PubMed  CAS  Google Scholar 

  15. Ohtani I, Baba Y, Suzuki T, Suzuki C, Kano M, Deka RC (2003) Why is otosclerosis of low prevalence in Japanese? Otol Neurotol 24(3):377–381

    Article  PubMed  Google Scholar 

  16. Kapur YP, Patt AJ (1966) Otosclerosis in South India. Acta Otolaryngol 61(4):353–360

    Article  PubMed  CAS  Google Scholar 

  17. Hueb MM, Goycoolea MV, Paparella MM, Oliveira JA (1991) Otosclerosis: the University of Minnesota temporal bone collection. Otolaryngol Head Neck Surg 105(3):396–405

    PubMed  CAS  Google Scholar 

  18. Guild SR (1944) Histologic otosclerosis. Ann Otol Rhinol Laryngol 53:246–247

    Google Scholar 

  19. CB Davenport BM, LB Frink (1933) The genetic factor in otosclerosis. Arch Otolaryngol 17:135–170, 340–383, 503–548

  20. Tod H (1907) Diseases of the ear. Oxford University Press, London, pp 120–124

  21. Manolidis S, Alford RL, Smith RJ, Ball C, Manolidis L (2003) Do the genes that cause otosclerosis reduce susceptibility to otitis media? Otol Neurotol 24(6):868–871

    Article  PubMed  Google Scholar 

  22. Larsson A (1960) Otosclerosis. A genetic and clinical study. Acta Otolaryngol Suppl 154:1–86

    PubMed  CAS  Google Scholar 

  23. Wullstein H (1958) Die audiologische und klinische Problemstellung bei der Operation der Stapesankylose (Stapedalyse und Fenestation). Zschr Laryng 37:368–374

    Google Scholar 

  24. Albrecht W (1922) Uber der Vererbung der konstitutionell sporadischen Taubstummheit der hereditaren Labyrinthscwerhorigkeit und der Otosclerose. Arch Ohr Nas Kehlkopfheilk 110:15–48

    Google Scholar 

  25. Bauer JSC (1925) Vererbung und Konstitution bei Ohrenkrankheiten. Zeitsscrift fur die gesamte Anatomie, Part II, Zeitschrift fur Konstitutionslehre 10:483–545

  26. Morrison AW, Bundey SE (1970) The inheritance of otosclerosis. J Laryngol Otol 84(9):921–932

    Article  PubMed  CAS  Google Scholar 

  27. Ben Arab S, Bonaiti-Pellie C, Belkahia A (1993) A genetic study of otosclerosis in a population living in the north of Tunisia. Ann Genet 36(2):111–116

    PubMed  CAS  Google Scholar 

  28. Schaap T, Gapany-Gapanavicius B (1978) The genetics of Otosclerosis. I. Distorted sex ratio. Am J Hum Genet 30(1):59–64

    PubMed  CAS  Google Scholar 

  29. Tato JM, De Lozzio CB, Valencia JI (1963) Chromosomal study in otosclerosis. Acta Otolaryngol 56:265–270

    Article  PubMed  CAS  Google Scholar 

  30. Jannuzzis S (1929) Gruppi sanguigni ed otosclerosi. Arch Ital Otol Rinol Laringol 40:499–518

    Google Scholar 

  31. McKenna MJ, Kristiansen AG, Bartley ML, Rogus JJ, Haines JL (1998) Association of COL1A1 and otosclerosis: evidence for a shared genetic etiology with mild osteogenesis imperfecta. Am J Otol 19(5):604–610

    PubMed  CAS  Google Scholar 

  32. McKenna MJ, Nguyen-Huynh AT, Kristiansen AG (2004) Association of otosclerosis with Sp1 binding site polymorphism in COL1A1 gene: evidence for a shared genetic etiology with osteoporosis. Otol Neurotol 25(4):447–450

    Article  PubMed  Google Scholar 

  33. Rodriguez L, Rodriguez S, Hermida J, Frade C, Sande E, Visedo G, Martin C, Zapata C (2004) Proposed association between the COL1A1 and COL1A2 genes and otosclerosis is not supported by a case-control study in Spain. Am J Med Genet A 128(1):19–22

    Article  Google Scholar 

  34. Tomek MS, Brown MR, Mani SR, Ramesh A, Srisailapathy CR, Coucke P, Zbar RI, Bell AM, McGuirt WT, Fukushima K, Willems PJ, Van Camp G, Smith RJ (1998) Localization of a gene for otosclerosis to chromosome 15q25–q26. Hum Mol Genet 7(2):285–290

    Article  PubMed  CAS  Google Scholar 

  35. Valhmu WB, Palmer GD, Rivers PA, Ebara S, Cheng JF, Fischer S, Ratcliffe A (1995) Structure of the human aggrecan gene: exon-intron organization and association with the protein domains. Biochem J 309(Pt 2):535–542

    PubMed  CAS  Google Scholar 

  36. Van Den Bogaert K, Govaerts PJ, Schatteman I, Brown MR, Caethoven G, Offeciers FE, Somers T, Declau F, Coucke P, Van de Heyning P, Smith RJ, Van Camp G (2001) A second gene for otosclerosis, OTSC2, maps to chromosome 7q34-36. Am J Hum Genet 68(2):495–500

    Article  Google Scholar 

  37. Alzoubi FQ, Ollier WR, Ramsden RT, Saeed SR (2007) No evidence of linkage between 7q33–36 locus (OTSC2) and otosclerosis in seven British Caucasian pedigrees. J Laryngol Otol 121(12):1140–1147

    Article  PubMed  CAS  Google Scholar 

  38. Chen W, Campbell CA, Green GE, Van Den Bogaert K, Komodikis C, Manolidis LS, Aconomou E, Kyamides Y, Christodoulou K, Faghel C, Giguere CM, Alford RL, Manolidis S, Van Camp G, Smith RJ (2002) Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3. J Med Genet 39(7):473–477

    Article  PubMed  CAS  Google Scholar 

  39. Brownstein Z, Goldfarb A, Levi H, Frydman M, Avraham KB (2006) Chromosomal mapping and phenotypic characterization of hereditary otosclerosis linked to the OTSC4 locus. Arch Otolaryngol Head Neck Surg 132(4):416–424

    Article  PubMed  Google Scholar 

  40. Van Den Bogaert K, De Leenheer EM, Chen W, Lee Y, Nurnberg P, Pennings RJ, Vanderstraeten K, Thys M, Cremers CW, Smith RJ, Van Camp G (2004) A fifth locus for otosclerosis, OTSC5, maps to chromosome 3q22–24. J Med Genet 41(6):450–453

    Article  CAS  Google Scholar 

  41. Iliadou V, Van Den Bogaert K, Eleftheriades N, Aperis G, Vanderstraeten K, Fransen E, Thys M, Grigoriadou M, Pampanos A, Economides J, Iliades T, Van Camp G, Petersen MB (2006) Monogenic nonsyndromic otosclerosis: audiological and linkage analysis in a large Greek pedigree. Int J Pediatr Otorhinolaryngol 70(4):631–637

    Article  PubMed  Google Scholar 

  42. Thys M, Van Den Bogaert K, Iliadou V, Vanderstraeten K, Dieltjens N, Schrauwen I, Chen W, Eleftheriades N, Grigoriadou M, Pauw RJ, Cremers CR, Smith RJ, Petersen MB, Van Camp G (2007) A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1. Eur J Hum Genet 15(3):362–368

    Article  PubMed  CAS  Google Scholar 

  43. Bel Hadj Ali I, Thys M, Beltaief N, Schrauwen I, Hilgert N, Vanderstraeten K, Dieltjens N, Mnif E, Hachicha S, Besbes G, Ben Arab S, Van Camp G (2008) A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9. Hum Genet 123(3):267–272

    Article  PubMed  Google Scholar 

  44. McKenna MJ, Mills BG, Galey FR, Linthicum FH Jr (1986) Filamentous structures morphologically similar to viral nucleocapsids in otosclerotic lesions in two patients. Am J Otol 7(1):25–28

    PubMed  CAS  Google Scholar 

  45. Arnold W, Friedmann I (1987) Detection of measles and rubella-specific antigens in the endochondral ossification zone in otosclerosis. Laryngol Rhinol Otol (Stuttg) 66(4):167–171

    Article  CAS  Google Scholar 

  46. Arnold W, Friedmann I (1988) Otosclerosisan—inflammatory disease of the otic capsule of viral aetiology? J Laryngol Otol 102(10):865–871

    Article  PubMed  CAS  Google Scholar 

  47. Arnold W, Friedmann I (1990) Immunohistochemistry of otosclerosis. Acta Otolaryngol Suppl 470:124–128 discussion 128–129

    PubMed  CAS  Google Scholar 

  48. McKenna MJ, Mills BG (1989) Immunohistochemical evidence of measles virus antigens in active otosclerosis. Otolaryngol Head Neck Surg 101(4):415–421

    PubMed  CAS  Google Scholar 

  49. Roald B, Storvold G, Mair IW, Mjoen S (1992) Respiratory tract viruses in otosclerotic lesions. An immunohistochemical study. Acta Otolaryngol 112(2):334–338

    PubMed  CAS  Google Scholar 

  50. Niedermeyer H, Arnold W, Neubert WJ, Hofler H (1994) Evidence of measles virus RNA in otosclerotic tissue. ORL J Otorhinolaryngol Relat Spec 56(3):130–132

    PubMed  CAS  Google Scholar 

  51. McKenna MJ KA (1994) Isolation and identification of nucleic acid sequences from celloidin embedded human bone sections using polymerase chain reaction. Proceedings of the fourth international academic conference on immunobiology in otology, rhinology and laryngology, Kugler, New York, pp 283–288

  52. Niedermeyer HP, Arnold W, Neubert WJ, Sedlmeier R (2000) Persistent measles virus infection as a possible cause of otosclerosis: state of the art. Ear Nose Throat J 79(8):552–554 556, 558 passim

    PubMed  CAS  Google Scholar 

  53. Niedermeyer HP, Arnold W (1995) Otosclerosis: a measles virus associated inflammatory disease. Acta Otolaryngol 115(2):300–303

    Article  PubMed  CAS  Google Scholar 

  54. Arnold W, Busch R, Arnold A, Ritscher B, Neiss A, Niedermeyer HP (2007) The influence of measles vaccination on the incidence of otosclerosis in Germany. Eur Arch Otorhinolaryngol 264(7):741–748

    Article  PubMed  Google Scholar 

  55. Shea JJ Jr (1998) A personal history of stapedectomy. Am J Otol 19(5 Suppl):S2–S12

    PubMed  Google Scholar 

  56. Grayeli AB, Palmer P, Tran Ba Huy P, Soudant J, Sterkers O, Lebon P, Ferrary E (2000) No evidence of measles virus in stapes samples from patients with otosclerosis. J Clin Microbiol 38(7):2655–2660

    PubMed  CAS  Google Scholar 

  57. Karosi T, Konya J, Petko M, Szabo LZ, Pytel J, Jori J, Sziklai I (2005) Two subgroups of stapes fixation: otosclerosis and pseudo-otosclerosis. Laryngoscope 115(11):1968–1973

    Article  PubMed  Google Scholar 

  58. Karosi T, Konya J, Szabo LZ, Pytel J, Jori J, Szalmas A, Sziklai I (2005) Codetection of measles virus and tumor necrosis factor-alpha mRNA in otosclerotic stapes footplates. Laryngoscope 115(7):1291–1297

    Article  PubMed  CAS  Google Scholar 

  59. Karosi T, Konya J, Szabo LZ, Sziklai I (2007) Measles virus prevalence in otosclerotic foci. Adv Otorhinolaryngol 65:93–106

    PubMed  Google Scholar 

  60. Karosi T, Konya J, Szabo LZ, Sziklai I (2004) Measles virus prevalence in otosclerotic stapes footplate samples. Otol Neurotol 25(4):451–456

    Article  PubMed  Google Scholar 

  61. Karosi T, Konya J, Petko M, Sziklai I (2005) Histologic otosclerosis is associated with the presence of measles virus in the stapes footplate. Otol Neurotol 26(6):1128–1133

    Article  PubMed  Google Scholar 

  62. Karosi T, Jokay I, Konya J, Szabo LZ, Pytel J, Jori J, Szalmas A, Sziklai I (2006) Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in connection with measles virus positivity. Laryngoscope 116(8):1427–1433

    Article  PubMed  CAS  Google Scholar 

  63. Karosi T, Jokay I, Konya J, Petko M, Szabo LZ, Pytel J, Jori J, Sziklai I (2006) Activated osteoclasts with CD51/61 expression in otosclerosis. Laryngoscope 116(8):1478–1484

    Article  PubMed  CAS  Google Scholar 

  64. Gantumur T, Niedermeyer HP, Neubert WJ, Arnold W (2006) Molecular detection of measles virus in primary cell cultures of otosclerotic tissue. Acta Otolaryngol 126(8):811–816

    Article  PubMed  CAS  Google Scholar 

  65. Karosi T, Konya J, Petko M, Szabo LZ, Pytel J, Jori J, Sziklai I (2006) Antimeasles immunoglobulin g for serologic diagnosis of otosclerotic hearing loss. Laryngoscope 116(3):488–493

    Article  PubMed  CAS  Google Scholar 

  66. Karosi T, Jokay I, Konya J, Petko M, Szabo LZ, Sziklai I (2007) Expression of measles virus receptors in otosclerotic, non-otosclerotic and in normal stapes footplates. Eur Arch Otorhinolaryngol 264(6):607–613

    Article  PubMed  Google Scholar 

  67. Niedermeyer HP, Gantumur T, Neubert WJ, Arnold W (2007) Measles virus and otosclerosis. Adv Otorhinolaryngol 65:86–92

    PubMed  CAS  Google Scholar 

  68. Lolov S, Edrev G, Kyurkchiev S (2007) Antimeasles immunoglobulin G and virus-neutralizing activity in sera of patients with otosclerosis. Adv Otorhinolaryngol 65:107–113

    PubMed  Google Scholar 

  69. Schmidt E (1933) Erblichkeit und Graviditat bei der Otosklerose. Arch Ohr Nas Kehlk Heilk 136:188–210

    Google Scholar 

  70. Cawthorne T (1955) Otosclerosis. J Laryngol Otol 69(7):437–456

    Article  PubMed  CAS  Google Scholar 

  71. Gristwood RE, Venables WN (1983) Pregnancy and otosclerosis. Clin Otolaryngol Allied Sci 8(3):205–210

    Article  PubMed  CAS  Google Scholar 

  72. Pearson E (1951) The effect of pregnancy on otosclerosis. Ann West Med Surg 5(5):477–482

    PubMed  CAS  Google Scholar 

  73. Greifenstein (1939) Schwangerschaftsunterbrechung und unfruchtbarmachung aus gesundheitlichen Grunden bei Otosklerose. Zeitschrift fur halsnasen und ohrenheilkunde 46:344–362

  74. Hall JG (1974) Otosclerosis in Norway, a geographical and genetical study. Acta Otolaryngol Suppl 324:1–20

    PubMed  CAS  Google Scholar 

  75. Lippy WH, Berenholz LP, Schuring AG, Burkey JM (2005) Does pregnancy affect otosclerosis? Laryngoscope 115(10):1833–1836

    Article  PubMed  Google Scholar 

  76. Jensen KJ, Nielsen HE, Elbrond O, Hansen HH (1979) Mineral content of skeletal bones in otosclerosis. Clin Otolaryngol Allied Sci 4(5):339–342

    Article  PubMed  CAS  Google Scholar 

  77. Lolov SR, Edrev GE, Kyurkchiev SD, Kehayov IR (1998) Elevated autoantibodies in sera from otosclerotic patients are related to the disease duration. Acta Otolaryngol 118(3):375–380

    Article  PubMed  CAS  Google Scholar 

  78. Grayeli AB, Sterkers O, Roulleau P, Elbaz P, Ferrary E, Silve C (1999) Parathyroid hormone-parathyroid hormone-related peptide receptor expression and function in otosclerosis. Am J Physiol 277(6 Pt 1):E1005–E1012

    PubMed  CAS  Google Scholar 

  79. Yoo TJ, Stuart JM, Kang AH, Townes AS, Tomoda K, Dixit S (1982) Type II collagen autoimmunity in otosclerosis and Meniere’s Disease. Science 217(4565):1153–1155

    Article  PubMed  CAS  Google Scholar 

  80. Bujia J, Alsalameh S, Jerez R, Sittinger M, Wilmes E, Burmester G (1994) Antibodies to the minor cartilage collagen type IX in otosclerosis. Am J Otol 15(2):222–224

    PubMed  CAS  Google Scholar 

  81. Solvsten Sorensen M, Nielsen LP, Bretlau P, Jorgensen MB (1988) The role of type II collagen autoimmunity in otosclerosis revisited. Acta Otolaryngol 105(3–4):242–247

    Article  PubMed  CAS  Google Scholar 

  82. Yoo TJ, Tomoda K, Stuart JM, Kang AH, Townes AS (1983) Type II collagen-induced autoimmune otospongiosis. A preliminary report. Ann Otol Rhinol Laryngol 92(2 Pt 1):103–108

    PubMed  CAS  Google Scholar 

  83. Harris JP, Woolf NK, Ryan AF (1986) A reexamination of experimental type II collagen autoimmunity: middle and inner ear morphology and function. Ann Otol Rhinol Laryngol 95(2 pt 1):176–180

    PubMed  CAS  Google Scholar 

  84. Menger DJ, Tange RA (2003) The aetiology of otosclerosis: a review of the literature. Clin Otolaryngol Allied Sci 28(2):112–120

    Article  PubMed  CAS  Google Scholar 

  85. Gregoriadis S, Zervas J, Varletzidis E, Toubis M, Pantazopoulos P, Fessas P (1982) HLA antigens and otosclerosis. A possible new genetic factor. Arch Otolaryngol 108(12):769–771

    PubMed  CAS  Google Scholar 

  86. Dahlqvist A, Diamant H, Dahlqvist SR, Cedergren B (1985) HLA antigens in patients with otosclerosis. Acta Otolaryngol 100(1–2):33–35

    Article  PubMed  CAS  Google Scholar 

  87. Miyazawa T, Tago C, Ueda H, Niwa H, Yanagita N (1996) HLA associations in otosclerosis in Japanese patients. Eur Arch Otorhinolaryngol 253(8):501–503

    Article  PubMed  CAS  Google Scholar 

  88. Pedersen U, Madsen M, Lamm LU, Elbrond O (1983) HLA-A, -B, -C antigens in otosclerosis. J Laryngol Otol 97(12):1095–1097

    Article  PubMed  CAS  Google Scholar 

  89. Chobaut JC, Bertrand D, Raffoux C, Wayoff M (1982) HLA antigens in otosclerosis. Am J Otol 3(3):241–242

    PubMed  CAS  Google Scholar 

  90. Thys M, Schrauwen I, Vanderstraeten K, Janssens K, Dieltjens N, Van Den Bogaert K, Fransen E, Chen W, Ealy M, Claustres M, Cremers CR, Dhooge I, Declau F, Claes J, Van de Heyning P, Vincent R, Somers T, Offeciers E, Smith RJ, Van Camp G (2007) The coding polymorphism T263I in TGF-beta1 is associated with otosclerosis in two independent populations. Hum Mol Genet 16(17):2021–2030

    Article  PubMed  CAS  Google Scholar 

  91. Lehnerdt G, Metz KA, Trellakis S, Jahnke K, Neumann A (2007) Signaling by way of type IB and II bone morphogenetic protein receptors regulates bone formation in otospongiosis. Laryngoscope 117(5):812–816

    Article  PubMed  CAS  Google Scholar 

  92. Schrauwen I, Thys M, Vanderstraeten K, Fransen E, Dieltjens N, Huyghe JR, Ealy M, Claustres M, Cremers CR, Dhooge I, Declau F, Van de Heyning P, Vincent R, Somers T, Offeciers E, Smith RJ, Van Camp G (2008) Association of bone morphogenetic proteins with otosclerosis. J Bone Miner Res 23(4):507–516

    Article  PubMed  CAS  Google Scholar 

  93. Kostenuik PJ, Shalhoub V (2001) Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des 7(8):613–635

    Article  PubMed  CAS  Google Scholar 

  94. Rosa-Ranal M, de la Cruz DA, Lorena-Rubio Y, Larrea F (2001) New paradigms in the regulation of bone metabolism. Rev Invest Clin 53(4):362–369

    PubMed  CAS  Google Scholar 

  95. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89(2):309–319

    Article  PubMed  CAS  Google Scholar 

  96. Nakamura M, Udagawa N, Nakamura H (2006) Bone remodeling and mineral homeostasis. Clin Calcium 16(1):46–53

    PubMed  CAS  Google Scholar 

  97. Zehnder AF, Kristiansen AG, Adams JC, Merchant SN, McKenna MJ (2005) Osteoprotegerin in the inner ear may inhibit bone remodeling in the otic capsule. Laryngoscope 115(1):172–177

    Article  PubMed  CAS  Google Scholar 

  98. Pedersen U, Sogaard H, Elbrond O (1984) Histological investigation of skin biopsies in otosclerosis and osteogenesis imperfecta. Arch Otorhinolaryngol 240(1):1–6

    Article  PubMed  CAS  Google Scholar 

  99. Mann W, Jonas I, Riede UN, Beck C (1980) A contribution to the pathogenesis of otosclerosis. Arch Otorhinolaryngol 226(3):161–176

    Article  PubMed  CAS  Google Scholar 

  100. Thalmann I, Thallinger G, Thalmann R (1987) Otosclerosis: a local manifestation of a generalized connective tissue disorder? Am J Otolaryngol 8(5):308–316

    Article  PubMed  CAS  Google Scholar 

  101. Nager GT (1988) Osteogenesis imperfecta of the temporal bone and its relation to otosclerosis. Ann Otol Rhinol Laryngol 97(6 Pt 1):585–593

    PubMed  CAS  Google Scholar 

  102. Ogilvie RF, Hall IS (1962) On the aetiology of otosclerosis. J Laryngol Otol 76:841–896

    Article  PubMed  CAS  Google Scholar 

  103. McKenna MJ, Kristiansen AG, Tropitzsch AS (2002) Similar COL1A1 expression in fibroblasts from some patients with clinical otosclerosis and those with type I osteogenesis imperfecta. Ann Otol Rhinol Laryngol 111(2):184–189

    PubMed  Google Scholar 

  104. Chen W, Meyer NC, McKenna MJ, Pfister M, McBride DJ Jr, Fukushima K, Thys M, Camp GV, Smith RJ (2007) Single-nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis. Clin Genet 71(5):406–414

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest statement

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Otolaryngology Department, AHEPA University Hospital, Aristotle’s University of Thessaloniki, 54006, Thessaloniki, Greece

    Konstantinos Markou & John Goudakos

Authors
  1. Konstantinos Markou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Goudakos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Konstantinos Markou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Markou, K., Goudakos, J. An overview of the etiology of otosclerosis. Eur Arch Otorhinolaryngol 266, 25–35 (2009). https://doi.org/10.1007/s00405-008-0790-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-008-0790-x

Keywords

Search

Navigation