Otoskleroza – Patofizjologia i mechanizm

Otoskleroza
Patofizjologia i mechanizm

Otoskleroza to patologiczny proces przebudowy kości ślimaka, w którym gęsta kość endochondralna torebki otycznej zostaje zastąpiona nieregularną kością gąbczastą, prowadzącą do upośledzenia funkcji słuchowej, najczęściej w okolicy strzemiączka. Etiopatogeneza jest wieloczynnikowa, obejmująca czynniki genetyczne (loci na chromosomach 6p, 9p, 1q, 3q, 6q, 7q, 15q, 16q, geny COL1A1, TGF-1, BMP2, BMP4, AGT M235T, ACE I/D), wirusowe (RNA wirusa odry wykrywane u 59%-100% pacjentów), hormonalne (większa częstość u kobiet, wpływ menopauzy, ciąży, antykoncepcji) oraz autoimmunologiczne (antygeny HLA, cytokiny, stres oksydacyjny). Proces przebiega w fazach: wczesnej (otospongioza), przejściowej i późnej (sklerotycznej), z lokalizacją zmian najczęściej w fissula ante fenestram. Klinicznie manifestuje się niedosłuchem przewodzeniowym (80-90% przypadków, unieruchomienie strzemiączka i sklerotyzacja okienka okrągłego), odbiorczym (około 8%, zajęcie ślimaka) lub mieszanym (2%). Dodatkowo występują szumy uszne (75%) i zawroty głowy (25%).

Patogeneza i mechanizm otosklerozy

Otoskleroza (łac. otosclerosis) jest patologicznym procesem przebudowy kości ślimaka, w którym prawidłowa, gęsta kość endochondralna torebki otycznej zostaje zastąpiona jednym lub wieloma ogniskami nieregularnie ułożonej kości gąbczastej, która następnie nieprawidłowo twardnieje i upośledza funkcję słuchową. Proces ten najczęściej obejmuje okolice strzemiączka.¹²

Etiopatogeneza otosklerozy

Dokładna etiopatogeneza otosklerozy pozostaje niejasna, mimo licznych proponowanych hipotez. Obecnie uważa się, że choroba ma podłoże wieloczynnikowe z komponentami genetycznymi, wirusowymi, zapalnymi i autoimmunologicznymi.¹²

Do najważniejszych czynników etiologicznych zalicza się:

Czynniki genetyczne – otoskleroza wykazuje związek z wieloma loci na chromosomach 6p, 9p, 1q, 3q, 6q, 7q, 15q i 16q oraz współczesnym locus na chromosomie 7q22.1. Różne geny, takie jak kolagen typu I (gen COL1A1), transformujący czynnik wzrostu-1 (TGF-1) wraz z genami BMP2 i BMP4, angiotensyna II z genami AGT M235T i ACE I/D mogą indukować otosklerozę.¹²
Czynniki wirusowe – zaproponowano rolę infekcji wirusem odry w patogenezie otosklerozy. RNA wirusa odry wykryto w płytce strzemiączka przy użyciu mikroskopii elektronowej i badań immunohistochemicznych u 59%-100% pacjentów.³⁴
Czynniki hormonalne – choroba występuje dwa razy częściej u kobiet niż u mężczyzn, co sugeruje rolę hormonów płciowych. Menopauza, ciąża i stosowanie doustnych środków antykoncepcyjnych mogą wpływać na przebieg choroby.³⁴
Czynniki autoimmunologiczne – reakcje autoimmunologiczne, antygeny HLA, cytokiny zapalne i regulatorowe, hormon przytarczyc, receptory peptydu związanego z hormonem przytarczyc oraz stres oksydacyjny mogą inicjować otosklerozę.⁴⁵

Fazy procesu przebudowy kostnej w otosklerozie

Proces patologiczny otosklerozy przebiega w kilku fazach:¹²³

Faza wczesna/aktywna (otospongioza) – charakteryzuje się resorpcją prawidłowej kości, często wokół naczyń krwionośnych, i zastąpieniem jej tkanką łączną włóknistą o wysokiej komórkowości. W tej fazie dominują histiocyty, osteoblasty i osteocyty, przy czym te ostatnie są najbardziej aktywną grupą komórek. Tworzy się lepsza mikrokrążenie.¹²
Faza przejściowa – osteoblasty stają się bardziej zaangażowane, co prowadzi do tworzenia nieregularnych ognisk nowej kości gąbczastej. Ta nowa kość barwi się intensywnie na niebiesko przy barwieniu hematoksyliną i eozyną i jest znana jako „niebieskie płaszcze Manassego”.¹
Faza późna/nieaktywna (otoskleroza właściwa) – charakteryzuje się tworzeniem gęstej kości sklerotycznej w obszarach wcześniejszej resorpcji. Powstaje zdezorganizowana kość o zwiększonej populacji osteocytów i powiększonych przestrzeniach szpikowych zawierających naczynia i inne tkanki łączne.¹²

Lokalizacja zmian otosklerotycznych

Zmiany otosklerotyczne najczęściej rozpoczynają się w obszarze fissula ante fenestram, zlokalizowanej między okienkiem owalnym a wyrostkiem cochleariformis ucha środkowego, rozprzestrzeniając się stamtąd poprzez kanały naczyniowe.¹²

Nie jest do końca jasne, dlaczego ten region wydaje się być epicentrum w większości przypadków otosklerozy, ale może to wynikać z faktu, że pozostałości chrząstki zarodkowej czasami utrzymują się w tej lokalizacji.¹

W zależności od lokalizacji zmian wyróżnia się:¹²

Otosklerozę strzemiączkową (stapedialną) – w 80-90% przypadków zmiany ograniczają się do przedniej części okienka owalnego i wpływają na jego funkcję poprzez zwapnienie więzadła pierścieniowatego lub zajęcie płytki strzemiączka, powodując charakterystyczny niedosłuch przewodzeniowy.
Otosklerozę labiryntową (ślimakową) – w około 8% przypadków proces obejmuje ślimak i części błędnika, powodując niedosłuch odbiorczy.
Otosklerozę mieszaną – około 2% pacjentów wykazuje zarówno zajęcie błędnika, jak i łańcucha kosteczek słuchowych.

Mechanizm niedosłuchu przewodzeniowego w otosklerozie

Niedosłuch przewodzeniowy w otosklerozie jest spowodowany dwoma głównymi mechanizmami:¹²

Unieruchomienie strzemiączka – zmiany sklerotyczne powodują unieruchomienie płytki strzemiączka w okienku owalnym, co znacznie upośledza jego ruchomość, a tym samym przewodzenie dźwięku do ucha wewnętrznego („sprzężenie kosteczkowe”).
Sklerotyzacja okienka okrągłego – dodatkowo okienko okrągłe ślimaka może również ulegać sklerotyzacji, co w podobny sposób upośledza ruch fal ciśnienia dźwięku przez ucho wewnętrzne („sprzężenie akustyczne”).

Podczas normalnego słyszenia strzemiączko, będące końcowym elementem łańcucha kosteczek, spoczywa w małym zagłębieniu (okienku owalnym) w bezpośrednim kontakcie z płynami ucha wewnętrznego. Cokolwiek, co zakłóca jego ruch, powoduje niedosłuch przewodzeniowy.¹²

Mechanizm niedosłuchu odbiorczego w otosklerozie

Mechanizm niedosłuchu odbiorczego w otosklerozie jest mniej dobrze poznany. Może on wynikać z kilku procesów:¹²³

Bezpośrednie uszkodzenie ślimaka – uszkodzenie struktur czuciowych w ślimaku i więzadle spiralnym przez proces lityczny lub przez uwolnienie enzymów proteolitycznych do ślimaka.
Uwolnienie enzymów hydrolitycznych – uwalnianie enzymów hydrolitycznych z ognisk spongiostycznych do struktur ucha wewnętrznego.
Zanik więzadła spiralnego – spowodowany zajęciem kości blaszkowej na wewnętrznej powierzchni torebki ślimaka.
Czynniki naczyniowe – zwyrodnienie prążka naczyniowego wpływające na funkcję słuchową.
Toksyczne metabolity – uwolnienie toksycznych metabolitów wytwarzanych przez ogniska otosklerotyczne do płynów ucha wewnętrznego.

Biochemiczne aspekty patogenezy otosklerozy

Na poziomie molekularnym proces przebudowy kości w otosklerozie jest regulowany przez szereg cytokin i cząsteczek sygnałowych, które odgrywają kluczową rolę w regulacji różnych procesów komórkowych, w tym przebudowy kości:¹²

Szlak RANKL/OPG/RANK – trójca osteoprotegeryna (OPG), receptor aktywator jądrowego czynnika kB (RANK) i ligand RANK (RANKL) kontroluje równowagę między resorpcją kości a tworzeniem kości. Badania sugerują, że zmiana ekspresji genu OPG (polimorfizm pojedynczego nukleotydu rs3102734 i rs2073618) jest związana z wystąpieniem otosklerozy.¹
Transformujący czynnik wzrostu β1 (TGF-β1) – może odgrywać kluczową rolę w rozwoju i patogenezie otosklerozy. Wariant intronowy rs8105161 wykazuje najsilniejszy związek z chorobą.¹²
Geny struktury kostnej – badania potwierdziły rolę genów RUNX2 i MEPE w regulacji struktury kostnej poprzez immunobarwienie przekrojów ucha wewnętrznego dla odpowiednich białek.¹

Manifestacje kliniczne patologii otosklerotycznej

Patologia otosklerotyczna może manifestować się różnorodnymi objawami klinicznymi:¹²³

Postępujący niedosłuch przewodzeniowy – główny objaw otosklerozy strzemiączkowej, wynikający z unieruchomienia strzemiączka.
Niedosłuch odbiorczy – wynikający z zajęcia struktur ślimaka w otosklerozie labiryntowej.
Niedosłuch mieszany – występuje, gdy otoskleroza dotyka zarówno kosteczek słuchowych (niedosłuch przewodzeniowy), jak i ślimaka lub komórek rzęsatych ucha wewnętrznego (niedosłuch odbiorczy).
Szumy uszne – występują u około 75% pacjentów i mogą wynikać z różnych mechanizmów, w tym zmniejszenia wibracji płynu ucha wewnętrznego, odsłonięcia szumów mięśniowych lub naczyniowych w przebiegu niedosłuchu przewodzeniowego, czy patologicznej waskularyzacji kości otosklerotycznej.¹²
Zawroty głowy i zaburzenia równowagi – występują u około 25% pacjentów, gdy ognisko otosklerotyczne wchodzi w kontakt z przychłonką, powodując zmianę w biochemii przychłonki.¹²

Modele leczenia otosklerozy w świetle jej patogenezy

Zrozumienie patogenezy otosklerozy ma bezpośrednie przełożenie na strategie terapeutyczne:¹²

Leczenie chirurgiczne – stapedektomia lub stapedotomia to zabiegi korygujące niedosłuch przewodzeniowy poprzez zastąpienie unieruchomionego strzemiączka protezą, która umożliwia przechodzenie drgań dźwiękowych z błony bębenkowej do płynów ucha wewnętrznego.¹²
Leczenie farmakologiczne – fluorki, bisfosfoniany trzeciej generacji i inhibitory cytokin mogą hamować proces przebudowy kostnej. Wykazano, że stosowanie bisfosfonianów prowadzi do poprawy radiologicznej na kontrolnych skanach, ale jedynie nieznacznej poprawy klinicznej u pacjentów.¹²
Aparaty słuchowe – wskazane w leczeniu pacjentów z otosklerozą, jednak w porównaniu z chirurgią strzemiączka, stosunek koszt-korzyść jest gorszy.¹
Chirurgia laserowa – zastosowanie lasera w chirurgii strzemiączka jest uważane za bezpieczną metodę, szczególnie laser CO2, który jest uważany za użyteczne urządzenie do operacji strzemiączka.¹
Implanty ślimakowe – mogą poprawić słuch u osób z otosklerozą ślimakową, tworząc nową drogę, którą dźwięki mogą dotrzeć do mózgu.¹

Kierunki badań nad patogenezą i przyszłością leczenia otosklerozy

Obecnie prowadzone są intensywne badania nad lepszym zrozumieniem patogenezy otosklerozy i opracowaniem nowych strategii terapeutycznych:¹²

Badania nad rolą wirusów – wyjaśnienie roli wirusa odry w patogenezie otosklerozy może prowadzić do nowych strategii zapobiegawczych i terapeutycznych.¹
Badania genetyczne – identyfikacja genów odpowiedzialnych za otosklerozę może umożliwić opracowanie terapii genowej i spersonalizowanych strategii leczenia.¹
Nowe terapie farmakologiczne – rozwój obiecujących terapii farmakologicznych opartych na lepszym zrozumieniu szlaków molekularnych zaangażowanych w patogenezę otosklerozy.¹
Modele zwierzęce – opracowanie modeli zwierzęcych do testowania nowych terapii jest kluczowym krokiem w kierunku lepszego leczenia otosklerozy.¹
Badania nad sekwencjonowaniem nowej generacji – zastosowanie RNA-sekwencjonowania i sekwencjonowania całego eksomu do badania molekularnych i genetycznych podstaw otosklerozy może pomóc w identyfikacji genów i procesów molekularnych zaburzonych w tkance otosklerotycznej.¹

Zrozumienie złożonej patogenezy otosklerozy pozostaje wyzwaniem dla badaczy i klinicystów. Choroba ta, charakteryzująca się nieprawidłową przebudową kości torebki otycznej, ma prawdopodobnie wieloczynnikowe podłoże, obejmujące komponenty genetyczne, wirusowe, hormonalne i autoimmunologiczne. Dalsze badania nad molekularnymi mechanizmami otosklerozy powinny przyczynić się do opracowania skuteczniejszych metod leczenia i potencjalnie zapobiegania tej chorobie.¹²³

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Materiały źródłowe

#1 Otosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK560671/
Otosclerosis is a pathological bone remodeling process in which the normal, dense endochondral bone of the otic capsule is replaced by one or more foci of irregularly laid spongy bone that subsequently hardens abnormally and impairs function; the condition most commonly involves the stapes region. […] The etiopathogenesis of otosclerosis remains unclear. Some of the multiple hypotheses that have been postulated include: […] Many loci on chromosomes 6p, 9p, 1q, 3q, 6q, 7q, 15q, and 16q have been associated with otosclerosis. […] The initial lesion often appears in the area of the fissula ante fenestram, located between the oval window and the cochleariform process of the middle ear, expanding from there via vascular channels. […] Multiple etiological factors, such as otosclerosis, likely contribute to the pathogenesis of bony dyscrasias. Bone remodeling occurs within the otic capsule with bone resorption followed by bone deposition, thus replacing normal bone with spongiotic bone.
#1 The Osseous Dissipation- Otosclerosis
https://biomedres.us/fulltexts/BJSTR.MS.ID.006477.php
Otosclerosis is a primary osteodystrophy of the otic capsule or a disorder of bone remodelling incriminating the stapes footplate or bony labyrinth of the inner ear. […] Of obscure and multifactorial pathogenesis, otosclerosis may arise due to genetic, viral, inflammatory or autoimmune components. […] Of obscure aetiology, otosclerosis is posited to denominate a multifactorial emergence such as Anatomical factors wherein fissula ante fenestram is incriminated along with persisting remnants of embryonic cartilage. […] Genetic factors of otosclerosis are associated with several loci situated upon chromosomes 6p, 9p, 1q, 3q, 6q, 7q, 15q, 16q and a contemporary locus upon chromosome 7q22.1. […] Additionally, diverse genes as type I collagen (COL1A1 gene), transforming growth factor-1 (TGF-1) with BMP2 and BMP4 genes, angiotensin II with AGT M235T and ACE I/D genes may induce otosclerosis.
#1 Otosclerosis | PPT
https://www.slideshare.net/slideshow/otosclerosis-238137407/238137407
Otosclerosis is a condition causing bilateral progressive conductive hearing loss. It is characterized by Cahart’s notch in bone conduction PTA. […] Otosclerosis is a disease affecting the bone of the middle ear that causes conductive or mixed hearing loss. It involves abnormal bone remodeling in the inner ear capsule, most commonly at the stapes footplate, causing stapes fixation and hearing loss. […] Otosclerosis is defined as hereditary localized disease of bone derived from the otic capsule characterized by alternating phases of bone formation and resorption. The mature lamellar bone is resorbed and replaced by an immature woven bone of greater thickness, cellularity and vascularity. […] The pathogenesis of conductive hearing loss involves narrowing and ankylosis of the annular ligament, especially the posterior vestibular joint space.
#1 Otospongiosis | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/otospongiosis-1?lang=us
Otospongiosis, also known as otosclerosis, is a primary osteodystrophy of the otic capsule (bony labyrinth of the inner ear). It is one of the leading causes of deafness in adults. […] The pathophysiology of otosclerosis is multifactorial and incompletely understood, with genetic, viral, inflammatory and autoimmune components. […] Two phases are described: early/active (otospongiosis) and late/inactive (otosclerosis). In the early phase, lesions consist predominantly of histiocytes, osteoblasts and osteocytes, the latter being the most active cell group. The bone around pre-existing blood vessels is absorbed, creating a better microcirculation. Eventually, osteoblasts become more involved, resulting in the formation of irregular foci of new spongy bone. This new bone appears densely blue on hematoxylin and eosinophil staining and is known as the blue mantles of Manasse. […] Retrofenestral otosclerosis usually occurs with fenestral involvement, so the two entities are considered a continuum rather than distinct.
#1 Otosclerosis: Practice Essentials, History of the Procedure, Epidemiology
https://emedicine.medscape.com/article/859760-overview
Otosclerosis is an osseous dyscrasia limited to the temporal bone that results in slow, progressive conductive hearing loss. […] Evidence has recently mounted that the measles virus plays an important role in gene activation of otosclerosis. This hypothesis is supported by a declining incidence of otosclerosis since measles vaccinations became widespread as well as finding measles virus RNA in the footplate of otosclerosis specimens. […] The exact cause of otosclerosis is unknown. Measles virus RNA is found in otosclerotic foci in footplates removed during surgery. Measles virus infection may activate the gene responsible for otosclerosis. […] The lesion is a pleomorphic replacement of normal bone with spongiotic or sclerotic bone. The histiologic disease progresses in stages. Bony resorption and replacement with new spongy bone characterize early lesions. Osteolytic osteocytes appear at the leading edge of the lesion, and sheets of connective tissue can be observed replacing the bone. Formation of dense sclerotic bone in areas of previous resorption signifies the late phase of otosclerosis. The result is disorganized bone, increased population of osteocytes, and enlarged marrow spaces containing vessels and other connective tissue.
#1 Otosclerosis | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/26432
It is unclear why this region appears to be the epicenter in most cases of otosclerosis, but it may be because embryonic cartilage remnants occasionally persist in that location. […] In most cases, lesions are limited to the anterior oval window and affect its function by calcifying the annular ligament or involving the stapes footplate. […] Multiple etiological factors, such as otosclerosis, likely contribute to the pathogenesis of bony dyscrasias.
#1 Otosclerosis: Practice Essentials, History of the Procedure, Epidemiology
https://emedicine.medscape.com/article/859760-overview
Initiating lesions often neighbor the fissula ante fenestram and expand via vascular channels. In 80-90% of patients, lesions are limited to the anterior oval window and affect its pathology by calcification of the annular ligament or by involving the stapes. Both processes result in characteristic conductive hearing loss. In 8% of patients, the process involves the cochlea and parts of the labyrinth (labyrinthine otosclerosis), resulting in sensorineural hearing loss. Approximately 2% of patients display both labyrinthine and ossicular chain involvement. […] Explanation of the clinical portion of sensorineural loss has been difficult, but investigators theorize that enzymes from the inner ear lesion diffuse via the spiral ligament to suppress neuron and hair cell activity.
#1 Otosclerosis – Wikipedia
https://en.wikipedia.org/wiki/Otosclerosis
Conductive hearing loss (CHL) in otosclerosis is caused by two main sites of involvement of the sclerotic (or scar-like) lesions. The best understood mechanism is fixation of the stapes footplate to the oval window of the cochlea. This greatly impairs movement of the stapes and therefore transmission of sound into the inner ear („ossicular coupling”). Additionally the cochlea’s round window can also become sclerotic, and in a similar way impair movement of sound pressure waves through the inner ear („acoustic coupling”). […] The mechanism of sensorineural hearing loss in otosclerosis is less well understood. It may result from direct injury to the cochlea and spiral ligament from the lytic process or from release of proteolytic enzymes into the cochlea. There are certainly a few well documented instances of sclerotic lesions directly obliterating sensory structures within the cochlea and spiral ligament, which have been photographed and reported post-mortem. Other supporting data includes a consistent loss of cochlear hair cells in patients with otosclerosis; these cells being the chief sensory organs of sound reception. A suggested mechanism for this is the release of hydrolytic enzymes into the inner ear structures by the spongiotic lesions.
#1 Otosclerosis Treatment in Farmington Hills | Michigan Ear Institute
https://michiganear.com/services/otosclerosis-stapedectomy/
Otosclerosis is a disease of the middle ear bones and sometimes the inner ear. […] If we had been able to examine your middle ear under the microscope before a hearing impairment developed we could have seen minute areas of both softening and hardening of the bone. This process may spread to the stapes, the inner ear, or to both sides. […] When otosclerosis spreads to the inner ear a sensorineural hearing impairment may result due to interference with the nerve function. This nerve impairment is called cochlear otosclerosis and one it develops it may be permanent. […] Usually otosclerosis spreads to the stapes or stirrup bone, the final link in the middle ear transformer chain. The stapes rests in the small groove, the oval window, in intimate contact with the inner ear fluids. Anything that interferes with its motion results in a conductive hearing impairment. This type of impairment is called stapedial otosclerosis and is usually correctable by surgery.
#1 Vertigo Associated with Otosclerosis and Stapes SurgeryâA Narrative Review
https://www.mdpi.com/1648-9144/59/8/1485
Otosclerosis is associated with inflammation, disturbed collagen expression, and the presence of viral receptors and antigens in the otosclerotic foci. At the molecular level, the bone remodelling process is regulated by a series of cytokines, signalling molecules that play a crucial role in regulating various cellular processes including bone remodelling. In otosclerosis, cytokines such as osteoprotegerin (OPG), receptor activator of nuclear factor kB (RANK), and RANK ligand (RANKL), as well as transforming growth factor Î²1 (TGF-Î²1), are involved in controlling the balance between bone resorption and bone formation. […] The presence of endolimphatic hydrops can be visualized on delayed three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) MRI images obtained after intravenous administration of gadolinium.
#1 Otosclerosis â analysis of factors influencing the imp…
https://otolaryngologypl.com/seo/article/01.3001.0015.8248/en?language=en
Otosclerosis is a disease that occurs only in humans, in the course of which there are foci of pathological ossification in the temporal bone. The etiology of the disease is not fully understood. […] Despite various factors being considered in the etiology of otosclerosis, the exact pathogenesis remains unknown. Genetic studies performed to date, failed to identify a specific gene responsible for otosclerosis, and theories of viral infections, autoimmunity, or a link to generalized bone diseases have not been able to explain why otosclerosis occurs only in the structure of the temporal bone, while the rest of the human skeleton remains completely unaffected. Recent studies on the role of the RANKL/OPG/RANK triad in the formation of otosclerotic foci suggest that the change in expression of the OPG gene (SNP â Single Nucleotide Polymorphism rs3102734 and rs2073618) is associated with the onset of otosclerosis.
#1 Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure | Nature Communications
https://www.nature.com/articles/s41467-022-32936-3
Several genes in the susceptibility loci converge on transforming growth factor beta receptor signalling pathways. […] We report an association at the TGFB1 locus at genome-wide significance, with the strongest association for the intronic variant rs8105161. […] Our results highlight several genes and signaling pathways for follow-up mechanistic studies.
#1 Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure | Nature Communications
https://www.nature.com/articles/s41467-022-32936-3
Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. […] The pathophysiology of otosclerosis is poorly understood. […] Although genetic, viral, immunologic and vascular factors have been implicated, the pathogenesis of otosclerosis remains poorly understood. […] We confirm a polygenic basis to otosclerosis. […] The association loci include several genes involved in the regulation of bone structure; we validated two of these genes, RUNX2 and MEPE, via immunostaining of inner ear sections for the corresponding proteins. […] The novel loci we identified are highly relevant because of known histopathologic and clinical features of otosclerosis. […] The effects on bone growth and remodeling in otosclerosis may be mediated by several pathways.
#1 Does stapes surgery improve tinnitus in patients with otosclerosis? | Brazilian Journal of Otorhinolaryngology
https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-does-stapes-surgery-improve-tinnitus-S1808869416301434
Otosclerosis (OS) is the primary disease of the human temporal bone characterized by conductive hearing loss and tinnitus. The exact pathogenesis of tinnitus in otosclerosis patients is not known and factors affecting the tinnitus outcome in otosclerosis patients are still controversial. […] The exact pathogenesis of tinnitus in OS is not known. Several authors have reported different possible mechanisms as follows: reduction of inner ear fluid vibration, unmasked muscular or vascular noises with conductive hearing loss, intravascular agglutination of red blood cells in the vessels of the cochlea, toxic metabolites produced by the otosclerotic foci, pathological vascularization of the otosclerotic bone and irritation of the nerve fibers by otosclerotic bone. […] The exact pathophysiology of tinnitus is unknown in patients with OS. The efferent auditory pathway has a modulatory effect on the outer hair cells of the Corti organ, which can buffer or amplify the message coming from the brain. When the auditory stimulus decreases, the central nervous system compensates by increasing the sensitivity of the outer hair cells and generates a phantom auditory perception as tinnitus.
#1 Otosclerosis | PPT
https://www.slideshare.net/slideshow/otosclerosis-238137407/238137407
Sensorineural hearing loss may occur due to the liberation of toxic metabolites into the fluids of the inner ear, vascular compromise, and alteration of the mechanism of motion within the cochlear duct. […] The otosclerotic focus could produce end organ or neural degeneration or both. […] Vertigo is produced when the otosclerotic focus comes in contact with the perilymph, resulting in a change in the biochemistry of the perilymph. […] Otosclerosis is a hereditary disorder characterized by abnormal bone remodeling in the otic capsule. It commonly causes conductive hearing loss but can rarely cause sensorineural hearing loss. […] The most common type of otosclerosis is stapedial otosclerosis, which results in a lesion in front of the oval window causing progressive conductive hearing loss.
#1 Pathophysiology of otosclerosis – PubMed
https://pubmed.ncbi.nlm.nih.gov/11300278/
Otosclerosis is a localized disease of bone remodeling within the otic capsule of the human temporal bone. Unlike other similar bone diseases, it does not occur outside of the temporal bone. These lesions seem to begin by resorption of stable otic capsule bone in adults, followed by a reparative phase with bone deposition. There are clearly genetic factors that lead to this disease, but measles virus infection and autoimmunity also may play contributing roles. […] Of the factors that may inhibit this process, fluorides, cytokine inhibitors, and bisphosphonates, third-generation bisphosphonates appear to hold the most promise.
#1 Otosclerosis Treatment in Farmington Hills | Michigan Ear Institute
https://michiganear.com/services/otosclerosis-stapedectomy/
The amount of hearing loss due to involvement of the stapes and the degree of nerve impairment present can be determined only by audiometric examination (hearing tests). […] There is no local treatment to the ear itself or any medication that will improve the hearing in persons with otosclerosis. […] In some cases a nutritional supplement containing fluoride may be prescribed to slow or stop the loss of hearing. […] The stapes operation (stapedectomy) is recommended for patients with otosclerosis who are candidates for surgery. […] The stapes prosthesis allows sound vibrations to pass from the eardrum to the inner ear fluids, correcting the conductive hearing loss. The hearing improvement obtained is usually permanent. […] In two percent (2%) of the cases the hearing may be further impaired due to the development of scar tissue, infection, blood vessel spasm, irritation of the inner ear, or a leak of inner ear fluid (fistula).
#1 Brazilian Society of Otology task force â Otosclerosis: evaluation and treatment | Brazilian Journal of Otorhinolaryngology
https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-brazilian-society-otology-task-force-S180886942300071X
The otosclerotic focus is identified on histologic sections of the temporal bone by its distinct appearance in the otic capsule after undergoing a remodeling process in which normal bone is replaced by otosclerotic bone. […] The pathophysiology of otosclerosis has not yet been fully elucidated, but environmental factors and unidentified genes are likely to play a significant role in it. […] The use of hearing aids is well indicated for the treatment of patients with otosclerosis. However, when compared with stapes surgery, the cost-benefit ratio is worse. […] The use of bisphosphonates has shown radiologic improvement on control scans, but only slight clinical improvement in patients. Higher-quality studies are still lacking to support their indication in patients with otosclerosis. […] The use of lasers should be considered in otosclerosis surgery. […] The use of the endoscope in stapes surgery is equally as safe as the use of the microscope.
#1 A Case of Otosclerosis Treated with One Shot Laser-Assisted Stapes Surgery
https://www.jkslms.or.kr/journal/view.html?doi=10.25289/ML.2015.4.2.81
Otosclerosis is an abnormal bone growth that causes fixation of stapes, leading to hearing loss. […] The exact mechanism as to how otosclerosis progress have yet been found; however, puberty, pregnancy, and menopause are thought to play an important role in disease progression. […] Many different laser device was used in stapes surgery. […] Therefore CO2 laser is considered the useful device for stapes surgery. […] Many reports demonstrate that one shot laser stapes surgery has advantage in terms of inner ear damage. […] Based on this case, application of one-shot laser stapes surgery is to be expected good surgical option for otosclerosis patient.
#1 Otosclerosis: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/22033-otosclerosis
Otosclerosis happens when irregular bone remodeling/growth occurs in your middle ear or, more rarely, your inner ear. […] In otosclerosis, irregular bone remodeling interferes with sounds ability to travel through your ear. […] Otosclerosis most often develops when the stapes bone (a small, triangular bone in your middle ear) fuses with the surrounding bone tissue. As a result, sound cant travel effectively. […] Stapedectomy (stay-puh-DEK-tuh-mee) is the medical term for otosclerosis surgery. During this procedure, an otolaryngologist places a prosthesis (replacement hearing bone) in your middle ear. This prosthesis bypasses the stapes bone, allowing sound waves to travel to your inner ear. […] Cochlear implants can improve hearing in people with cochlear otosclerosis. (Your cochlea is a spiral, fluid-filled structure in your inner ear that helps with hearing.) A cochlear implant bypasses your inner ear structures and creates a new pathway on which sounds can travel to your brain. […] Without treatment, otosclerosis may get worse over time. In some cases, it can spread to your inner ear and cause cochlear otosclerosis.
#1 Progress Toward Understanding the Etiology of Otosclerosis and Implications for Future Management
https://www.jstage.jst.go.jp/article/otoljpn/19/2/19_2_113/_article/-char/en
Otosclerosis is a disease of the otic capsule that is among the most common causes of acquired hearing loss. […] During the last 15 years, our laboratory has focused on elucidating the molecular pathology of otosclerosis with the long-term goal of developing better forms of therapy. […] These studies have brought us to the point where we are ready to consider and develop new and innovative treatment strategies. […] We have identified a promising pharmacological treatment, have begun to develop and test a drug formulation for use in humans, and have developed an animal model with which to test this therapy.
#1
https://journals.lww.com/otology-neurotology/fulltext/2007/10000/otosclerosis_in_the_incus__fact_or_fantasy_.28.aspx
A series of articles have been published during the last 3 years about the pathogenesis of otosclerosis. […] These reports clearly call the attention to the fact that all histologically otosclerotic stapes fixations are associated with the presence of measles virus genomic RNA. […] The otic capsule shows inevitable affinity to persisting measles virus infection and replication, which coincides with the organ-specific localization of otosclerotic foci. […] The subsequent inflammatory process is characterized by pseudovascular, irregular, and hypercellular absorption lacunae bordered by numerous osteoclasts and multi-nucleated giant cells in the active stage. […] In contrast, the inactive phase of otosclerosis is featured by almost total absence of bone-derived cells with woven and mosaiclike pattern of cement lines. […] Today, we do think, that the diagnosis of otosclerosis cannot be established without detecting low antimeasles immunoglobulin G in the serum and/or detecting measles virus RNA in the affected bone specimen.
#1
https://discovery.ucl.ac.uk/1417191/
Otosclerosis is a common form of conductive hearing loss. It is characterised by abnormal bone remodelling within the otic capsule, leading to formation of sclerotic lesions of the temporal bone. Encroachment of these lesions on to the footplate of the stapes in the middle ear leads to stapes fixation and subsequent conductive hearing loss. […] The research presented in this thesis examines the molecular and genetic basis of otosclerosis using two next generation sequencing technologies; RNA-sequencing and Whole Exome Sequencing. RNAsequencing has provided human stapes transcriptomes for healthy and diseased stapes, and in combination with pathway analysis has helped identify genes and molecular processes dysregulated in otosclerotic tissue. Whole Exome Sequencing has been employed to investigate rare variants that segregate with otosclerosis in affected families, and has been followed by a variant filtering strategy, which has prioritised genes found to be dysregulated during RNA-sequencing. This has identified multiple variants predicted to be involved in splicing within genes involved in the bone disorder Osteogenesis Imperfecta, indicating a shared genetic aetiology for this condition and otosclerosis and a possible disease mechanism involving alternative splicing in the stapes. […] It is hoped that long term, this research will help reveal disease mechanisms and thereby improve treatment options for otosclerosis patients.
#1 Brazilian Society of Otology task force â Otosclerosis: evaluation and treatment | Brazilian Journal of Otorhinolaryngology
https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-brazilian-society-otology-task-force-S180886942300071X
The pathophysiology of otosclerosis has not yet been fully elucidated, but environmental factors and unidentified genes are likely to play a significant role in it. […] The classic presentation of otosclerosis consists of progressive conductive hearing loss in adulthood. However, the type of deafness depends on the location and extension of the otosclerotic foci. […] The ossicular chain and otic capsule undergo endochondral ossification during their development and, after this process, minimal bone remodeling occurs throughout life. Bone remodeling has reduced activity in the petrous portion of the temporal bone and is almost null near the perilymphatic space. […] Several cytokines are likely to be active in otosclerotic lesions, and the disinhibition of one or more of these cytokines may trigger the development of otosclerosis.
#2 Otosclerosis | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/26432
Otosclerosis (oto, „of the ear,” and sclerosis, „abnormal hardening”) is a pathological bone remodeling process that affects the middle and inner ears. […] In otosclerosis, the normal, dense endochondral bone of the otic capsule around the inner ear labyrinth is replaced by irregularly laid spongy bone, which subsequently hardens and leads to fixation of the stapes footplate. […] The etiopathogenesis of otosclerosis remains unclear. Some of the multiple hypotheses that have been postulated include: […] Many loci on chromosomes 6p, 9p, 1q, 3q, 6q, 7q, 15q, and 16q have been associated with otosclerosis. […] Additionally, other bone metabolism abnormalities, such as osteogenesis imperfecta, and multiple genes associated with bone remodeling have been considered potential causes of otosclerosis, including type I collagen (COL1A1), TGF-beta 1 (BMP2 and BMP4), angiotensin II (AGT M235T and ACE I/D), autoimmune reactions, human leucocyte antigen, inflammatory and regulatory cytokines, parathyroid hormone and expression of parathyroid hormone-related peptide receptors, and oxidative stress.
#2 Otospongiosis | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/otospongiosis-1?lang=us
Otospongiosis, also known as otosclerosis, is a primary osteodystrophy of the otic capsule (bony labyrinth of the inner ear). It is one of the leading causes of deafness in adults. […] The pathophysiology of otosclerosis is multifactorial and incompletely understood, with genetic, viral, inflammatory and autoimmune components. […] Two phases are described: early/active (otospongiosis) and late/inactive (otosclerosis). In the early phase, lesions consist predominantly of histiocytes, osteoblasts and osteocytes, the latter being the most active cell group. The bone around pre-existing blood vessels is absorbed, creating a better microcirculation. Eventually, osteoblasts become more involved, resulting in the formation of irregular foci of new spongy bone. This new bone appears densely blue on hematoxylin and eosinophil staining and is known as the blue mantles of Manasse. […] Retrofenestral otosclerosis usually occurs with fenestral involvement, so the two entities are considered a continuum rather than distinct.
#2
#2 OTOSCLEROSIS: A Review for Audiologists – Article 1226
https://www.audiologyonline.com/articles/otosclerosis-a-review-for-audiologists-1226
Otosclerosis is a common condition affecting the bone of the otic capsule in 7.3% of Caucasian males and 10.3% of Caucasian females. […] Histologically, otosclerosis is characterized by 2 phases: 1) otospongiosis; and, 2) otosclerosis. In otospongiosis, affected bone becomes hypervascular and osteoclasts and osteolytic osteocytes cause enlargement of the vascular spaces of the bone. After otospongiosis, bone deposition characterizes the otosclerosis phase. […] While the etiology of otosclerosis remains unknown, there are two main theories regarding its origin; genetic and viral. […] Otosclerosis seems inherited in approximately 50% of cases. It may be inherited as an autosomal dominant trait with 25-40 percent penetrance and is more common in females. […] Electron microscopy has demonstrated structures similar to viral nucleocapsids in cells of otospongiotic lesions. Immunohistochemical studies revealed measles virus nucleocapsid protein in cells associated with otospongiosis. […] Polymerase chain reaction (PCR) studies have supported these observations and also found anti-measles IgG in the perilymph of patients with otosclerosis.
#2 Otosclerosis – wikidoc
https://www.wikidoc.org/index.php/Otosclerosis
Otosclerosis is an osseous dyscrasia of the otic capsule, which should be an endochondral dense bony part in the labyrinth, replaced by irregularly laid spongy bone leading to the fixation of stapes. […] Many genetic factors contribute to the development of otosclerosis. And it is an autosomal dominant inheritance with incomplete penetrance. […] Accumulation of bone deposits because of increased bone remodeling which is bone resorption followed by bone deposition in the otic capsule result in otosclerosis. […] Audiological findings are directly proportionate to the extent of bone remodeling. […] Bone remodeling happens in 3 phases: Otospongiosis, Transitional phase, Otosclerotic phase characterized by spongy bone deposits developing into dense bone that narrows the microcirculation previously developed in the otospongiosis phase. […] The lesions occur mostly in the anterior to the oval window by calcifying of annular ligament or by involving stapes footplate (80%).
#2 Otosclerosis | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/26432
In more than half of patients presenting with otosclerosis, there is a family history of the condition. […] The prevalence of otosclerosis is twice as great in women compared to men, suggesting the role of sex hormones. […] A role for measles virus infection in the pathogenesis of otosclerosis has been postulated. […] Bone remodeling occurs within the otic capsule with bone resorption followed by bone deposition, thus replacing normal bone with spongiotic bone. […] Early in the disease process, osteoclasts appear in the lesion, and their activity results in connective tissue replacing normal bone. […] The initial lesion often appears in the area of the fissula ante fenestram, located between the oval window and the cochleariform process of the middle ear, expanding from there via vascular channels.
#2 Otosclerosis is a treatable cause of hearing loss.
https://lmhofmeyr.co.za/conditions/hearing/otosclerosis/
If it involves the ossicles, especially the stapes a slow progressive conductive hearing loss is seen. The progress is often stepwise with periods of quiescence alternating with periods of deterioration. The hearing loss may be asymmetric in the two ears. The most common focus of otosclerosis (80-90%) is the fistula ante fenestral just in front of the oval window. Obliterative otosclerosis refers to otosclerosis that obliterates the whole oval window. In some cases, otosclerosis involves the whole footplate of the stapes but not the walls of the oval window. This is referred to as a biscuit footplate. Although otosclerosis involves the round window in 30-50%, hearing loss in this scenario is extremely rare and occurs only if the whole round window is involved. […] Less commonly it may involve the cochlea and cause sensorineural hearing loss. In the absence of otosclerotic changes in the cochlea, it is speculated that the release of toxic enzymes or metabolites in the cochlear fluid is responsible for the sensorineural component. In these cases, it is typical for patients to present with mixed hearing loss.
#2 Otosclerosis: Causes, Symptoms, and Treatments
https://patient.info/ears-nose-throat-mouth/hearing-problems/otosclerosis
It is also thought that a virus may play a part and the measles virus has been suggested. Indeed, the number of people diagnosed with otosclerosis seems to have decreased since the measles virus vaccination has been given. It may be that a genetic tendency to develop otosclerosis is inherited by some people. Then a trigger, such as a viral infection, actually causes the condition to develop. […] It is also possible that low levels of fluoride may have something to do with the development of otosclerosis. The number of cases of otosclerosis in the UK went down after fluoride was routinely added to drinking water. However, this possible link with low levels of fluoride is controversial. […] Otosclerosis mainly affects the tiny bone (ossicle) called the stirrup (stapes). To have normal hearing, the ossicles need to be able to move freely in response to sound waves. In otosclerosis, abnormal bone material grows around the stapes bone. The foot of the stapes, where it attaches to the cochlea, is usually where the condition starts. The abnormal bone reduces the movement of the stapes, which reduces the amount of sound that is transferred to the cochlea. The growth of the abnormal bone is very gradual. However, eventually the stapes can become fixed, or fused, with the bone of the cochlea. This can cause severe hearing loss. The hearing loss is known as conductive hearing loss because sound vibrations cannot be conducted (transmitted) from the stapes to the cochlea.
#2 Otosclerosis Treatment in Dallas, Fort Worth and Frisco, TX | Dallas Ear Institute
https://www.dallasear.com/services/the-center-for-otosclerosis/what-is-otosclerosis/
Otosclerosis is a disease of the middle ear bones and sometimes the inner ear. Otosclerosis is a common cause of hearing impairment and is rarely hereditary. […] If we had been able to examine your middle ear under the microscope before a hearing impairment developed we could have seen minute areas of both softening and hardening of the bone. This process may spread to the stapes, the inner ear, or to both sides. […] Usually otosclerosis spreads to the stapes or stirrup bone, the final link in the middle ear transformer chain. The stapes rests in the small groove, the oval window, in intimate contact with the inner ear fluids. Anything that interferes with its motion results in a conductive hearing impairment. This type of impairment is called stapedial otosclerosis and is usually correctable by surgery. The amount of hearing loss due to involvement of the stapes and the degree of nerve impairment present can be determined only by audiometric examination (hearing tests).
#2 CT Grading of Otosclerosis | American Journal of Neuroradiology
http://www.ajnr.org/content/30/7/1435
Otosclerosis is an idiopathic disease that can result in spongiosis or sclerosis of portions of the petrous bone leading to conductive, sensorineural, or mixed hearing loss. […] The mechanism of sensorineural hearing loss in otosclerosis is less well understood. It may result from direct injury to the cochlea and spiral ligament from the lytic process or from release of proteolytic enzymes into the cochlea. […] The CT grading of otosclerosis published by Symons and Fanning is based on anatomic localization of disease. Focal spongiotic areas, sclerotic areas, and double ring effect are included, but classification is based on the presence of these at a particular location around the cochlea. […] The Symons/Fanning classification allows for more precise localization of disease afforded by these more advanced CT scanners. The Symons/Fanning classification also encompasses all types of cochlear disease changes: spongiotic, sclerotic, and the double ring effect.
#2 Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure | Nature Communications
https://www.nature.com/articles/s41467-022-32936-3
Several genes in the susceptibility loci converge on transforming growth factor beta receptor signalling pathways. […] We report an association at the TGFB1 locus at genome-wide significance, with the strongest association for the intronic variant rs8105161. […] Our results highlight several genes and signaling pathways for follow-up mechanistic studies.
#2 Dynamic Molecular Markers of Otosclerosis in the Human Cochlea.
https://escholarship.org/uc/item/0dd3g5f8
OBJECTIVE: To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis. […] CONCLUSIONS: Our results propose that the activity and function of TGF-1 may play a key role in the development and pathogenesis of otosclerosis.
#2 Otosclerosis: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/22033-otosclerosis
Otosclerosis happens when irregular bone remodeling/growth occurs in your middle ear or, more rarely, your inner ear. […] In otosclerosis, irregular bone remodeling interferes with sounds ability to travel through your ear. […] Otosclerosis most often develops when the stapes bone (a small, triangular bone in your middle ear) fuses with the surrounding bone tissue. As a result, sound cant travel effectively. […] Stapedectomy (stay-puh-DEK-tuh-mee) is the medical term for otosclerosis surgery. During this procedure, an otolaryngologist places a prosthesis (replacement hearing bone) in your middle ear. This prosthesis bypasses the stapes bone, allowing sound waves to travel to your inner ear. […] Cochlear implants can improve hearing in people with cochlear otosclerosis. (Your cochlea is a spiral, fluid-filled structure in your inner ear that helps with hearing.) A cochlear implant bypasses your inner ear structures and creates a new pathway on which sounds can travel to your brain. […] Without treatment, otosclerosis may get worse over time. In some cases, it can spread to your inner ear and cause cochlear otosclerosis.
#2 Otosclerosis is a treatable cause of hearing loss.
https://lmhofmeyr.co.za/conditions/hearing/otosclerosis/
Tinnitus occurs in 75% and dizziness and vertigo in 25% of patients. The exact mechanism for the development of vertigo is unknown. […] Some conditions may mimic the hearing loss in otosclerosis. These include superior canal dehiscence syndrome (SCDS), tympanosclerosis, osteogenesis imperfecta, and other middle ear conditions. It is of vital importance that these conditions are considered before surgery is attempted. […] The most common surgical procedure performed nowadays is a stapedotomy. A small hole is created in the footplate of the stapes where after the prosthesis is placed from the incus into the stapedotomy hole. This re-establishes the conduction of sound. Mobilizing the fixed stapes is not effective and refixation always occurs. In some cases of cochlear otosclerosis with mixed or sensorineural hearing loss cochlear implantation (CI) may be the only option.
#2 Brazilian Society of Otology task force â Otosclerosis: evaluation and treatment | Brazilian Journal of Otorhinolaryngology
https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-brazilian-society-otology-task-force-S180886942300071X
The otosclerotic focus is identified on histologic sections of the temporal bone by its distinct appearance in the otic capsule after undergoing a remodeling process in which normal bone is replaced by otosclerotic bone. […] The pathophysiology of otosclerosis has not yet been fully elucidated, but environmental factors and unidentified genes are likely to play a significant role in it. […] The use of hearing aids is well indicated for the treatment of patients with otosclerosis. However, when compared with stapes surgery, the cost-benefit ratio is worse. […] The use of bisphosphonates has shown radiologic improvement on control scans, but only slight clinical improvement in patients. Higher-quality studies are still lacking to support their indication in patients with otosclerosis. […] The use of lasers should be considered in otosclerosis surgery. […] The use of the endoscope in stapes surgery is equally as safe as the use of the microscope.
#2 Otosclerosis & Stapedotomy | Hearing Loss Treatment | Suburban ENT
https://subent.com/expertise/otologyneurology/stapedotomy/
Otosclerosis usually presents as a gradual onset of progressive hearing loss in one or both ears. Few types of hearing loss can be surgically corrected as well as otosclerosis. A surgical procedure, known as laser stapedotomy, can usually correct most of the hearing loss related to otosclerosis. Generally, the operation is curative for this condition. If a patient is not a candidate for the surgery, or does not want to have surgery performed, wearing a hearing aid is also an option. […] Stapedotomy is an operation to remove (actually bypass) the stapes bone, replacing it with a prosthesis. […] The bottom of the stapes, called the footplate region, makes direct contact with the inner ear, and it is at this point that otosclerosis interferes with the transmission of sound. In otosclerosis, there is an overgrowth of bone around the footplate, causing the stapes bone to be fixed and unable to vibrate. Stapedotomy is performed to bypass the immobile stapes with an artificial piston prosthesis.
#2 Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure | Nature Communications
https://www.nature.com/articles/s41467-022-32936-3
Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. […] The pathophysiology of otosclerosis is poorly understood. […] Although genetic, viral, immunologic and vascular factors have been implicated, the pathogenesis of otosclerosis remains poorly understood. […] We confirm a polygenic basis to otosclerosis. […] The association loci include several genes involved in the regulation of bone structure; we validated two of these genes, RUNX2 and MEPE, via immunostaining of inner ear sections for the corresponding proteins. […] The novel loci we identified are highly relevant because of known histopathologic and clinical features of otosclerosis. […] The effects on bone growth and remodeling in otosclerosis may be mediated by several pathways.
#3 Otosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK560671/
Early in the disease process, osteoclasts appear in the lesion, and their activity results in connective tissue replacing normal bone. Later, dense sclerotic bone forms in the areas of bony resorption. The result is disorganized bone, increased osteocytes, and widened marrow spaces with vascular and connective tissue. […] The prevalence of otosclerosis is twice as great in women compared to men, suggesting the role of sex hormones. […] A role for measles virus infection in the pathogenesis of otosclerosis has been postulated. Measles virus ribonucleic acid has been detected in the footplate of the stapes on electron microscopy and immunohistochemical studies in 59%-100% of patients.
#3 Otosclerosis – wikidoc
https://www.wikidoc.org/index.php/Otosclerosis
Otosclerosis is an osseous dyscrasia of the otic capsule, which should be an endochondral dense bony part in the labyrinth, replaced by irregularly laid spongy bone leading to the fixation of stapes. […] Many genetic factors contribute to the development of otosclerosis. And it is an autosomal dominant inheritance with incomplete penetrance. […] Accumulation of bone deposits because of increased bone remodeling which is bone resorption followed by bone deposition in the otic capsule result in otosclerosis. […] Audiological findings are directly proportionate to the extent of bone remodeling. […] Bone remodeling happens in 3 phases: Otospongiosis, Transitional phase, Otosclerotic phase characterized by spongy bone deposits developing into dense bone that narrows the microcirculation previously developed in the otospongiosis phase. […] The lesions occur mostly in the anterior to the oval window by calcifying of annular ligament or by involving stapes footplate (80%).
#3 Otosclerosis | PPT
https://www.slideshare.net/slideshow/otosclerosis-238137407/238137407
Sensorineural hearing loss may occur due to the liberation of toxic metabolites into the fluids of the inner ear, vascular compromise, and alteration of the mechanism of motion within the cochlear duct. […] The otosclerotic focus could produce end organ or neural degeneration or both. […] Vertigo is produced when the otosclerotic focus comes in contact with the perilymph, resulting in a change in the biochemistry of the perilymph. […] Otosclerosis is a hereditary disorder characterized by abnormal bone remodeling in the otic capsule. It commonly causes conductive hearing loss but can rarely cause sensorineural hearing loss. […] The most common type of otosclerosis is stapedial otosclerosis, which results in a lesion in front of the oval window causing progressive conductive hearing loss.
#3 Does stapes surgery improve tinnitus in patients with otosclerosis? | Brazilian Journal of Otorhinolaryngology
https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-does-stapes-surgery-improve-tinnitus-S1808869416301434
Otosclerosis (OS) is the primary disease of the human temporal bone characterized by conductive hearing loss and tinnitus. The exact pathogenesis of tinnitus in otosclerosis patients is not known and factors affecting the tinnitus outcome in otosclerosis patients are still controversial. […] The exact pathogenesis of tinnitus in OS is not known. Several authors have reported different possible mechanisms as follows: reduction of inner ear fluid vibration, unmasked muscular or vascular noises with conductive hearing loss, intravascular agglutination of red blood cells in the vessels of the cochlea, toxic metabolites produced by the otosclerotic foci, pathological vascularization of the otosclerotic bone and irritation of the nerve fibers by otosclerotic bone. […] The exact pathophysiology of tinnitus is unknown in patients with OS. The efferent auditory pathway has a modulatory effect on the outer hair cells of the Corti organ, which can buffer or amplify the message coming from the brain. When the auditory stimulus decreases, the central nervous system compensates by increasing the sensitivity of the outer hair cells and generates a phantom auditory perception as tinnitus.
#3 Otosclerosis – American Hearing Research Foundation
https://www.american-hearing.org/disease/otosclerosis/
While the medical and research communities understand what happens to the ear as a result of otosclerosis, what actually triggers the disorder remains uncertain. Current thinking leans toward the belief that there is likely an interplay among multiple factors and that the genetic component may not be enough to set the disease in motion. Many experts believe that otosclerosis must be triggered by a combination of genetic, environmental, hormonal, and/or other factors. […] Research suggests that otosclerosis may be linked in some way to the following: Genetics: Otosclerosis tends to run in families. Estimates vary, but many (perhaps up to 50%) of those with the disorder have a gene linked to it. […] Autoimmunity: Some researchers believe that otosclerosis may be linked to an autoimmune response by the body. This type of response generally happens when the persons immune system becomes confused, acting against healthy body tissue as if it were a pathogen. Frequently, environmental and genetic factors play a role in the activation of an autoimmune response by the body. […] Clearly, otosclerosis is a complex disease. And both the intricacy and relative inaccessibility of the inner ear raise additional challenges in fully understanding it.
#4 The Osseous Dissipation- Otosclerosis
https://biomedres.us/fulltexts/BJSTR.MS.ID.006477.php
Sex hormones, autoimmune reaction, human leucocyte antigen (HLA), inflammatory or regulatory cytokines, parathyroid hormone, parathyroid hormone-related peptide receptors and oxidative stress may initiate otosclerosis. […] Hereditary factors wherein an estimated 50% subjects with otosclerosis demonstrate a family history. […] Individuals with hereditary otosclerosis are associated with an antecedent disease onset. […] Majority of instances depict an autosomal dominant mode of inheritance accompanied by reduced penetrance in nearly ~40% subjects and variable expression of disease. […] Viral infection is implicated in the emergence of otosclerosis. […] Ribonucleic acid (RNA) of measles virus may be discerned within footplate of stapes upon ultrastructural examination and immunohistochemistry. […] Additionally, factors such as menopause, trauma, bone dyscrasia or major surgery may initiate or aggravate otosclerosis.
#4 A Case of Otosclerosis Treated with One Shot Laser-Assisted Stapes Surgery
https://www.jkslms.or.kr/journal/view.html?doi=10.25289/ML.2015.4.2.81
Otosclerosis is an abnormal bone growth that causes fixation of stapes, leading to hearing loss. […] The exact mechanism as to how otosclerosis progress have yet been found; however, puberty, pregnancy, and menopause are thought to play an important role in disease progression. […] Many different laser device was used in stapes surgery. […] Therefore CO2 laser is considered the useful device for stapes surgery. […] Many reports demonstrate that one shot laser stapes surgery has advantage in terms of inner ear damage. […] Based on this case, application of one-shot laser stapes surgery is to be expected good surgical option for otosclerosis patient.
#5 Otosclerosis | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/26432
Otosclerosis (oto, „of the ear,” and sclerosis, „abnormal hardening”) is a pathological bone remodeling process that affects the middle and inner ears. […] In otosclerosis, the normal, dense endochondral bone of the otic capsule around the inner ear labyrinth is replaced by irregularly laid spongy bone, which subsequently hardens and leads to fixation of the stapes footplate. […] The etiopathogenesis of otosclerosis remains unclear. Some of the multiple hypotheses that have been postulated include: […] Many loci on chromosomes 6p, 9p, 1q, 3q, 6q, 7q, 15q, and 16q have been associated with otosclerosis. […] Additionally, other bone metabolism abnormalities, such as osteogenesis imperfecta, and multiple genes associated with bone remodeling have been considered potential causes of otosclerosis, including type I collagen (COL1A1), TGF-beta 1 (BMP2 and BMP4), angiotensin II (AGT M235T and ACE I/D), autoimmune reactions, human leucocyte antigen, inflammatory and regulatory cytokines, parathyroid hormone and expression of parathyroid hormone-related peptide receptors, and oxidative stress.