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OTOSCLEROSIS: PATHOPHYSIOLOGY, CLINICAL MANIFESTATIONS,
DIAGNOSIS, AND ADVANCES IN TREATMENT
Nishanbayeva Firuza Murodovna
Senior lecturer of the Alfraganus university
ORCID ID: 0009-0007-0093-4806
Email: Drmalikovafiruza8286@mail.ru
https://doi.org/10.5281/zenodo.14890905
Introduction
Otosclerosis is a pathological bone remodeling disorder affecting the middle and inner
ear. The term derives from "oto," meaning ear, and "sclerosis," referring to abnormal hardening.
Initially described by Antonio Maria Valsalva in 1735 and later characterized pathologically by
Adam Politzer in 1839, otosclerosis involves the replacement of the normal dense
endochondral bone of the otic capsule with irregular spongy bone, which eventually hardens
and leads to fixation of the stapes footplate.
This condition primarily results in conductive hearing loss while preserving the normal
appearance of the tympanic membrane. However, in some cases, a reddish hue on the cochlear
promontory, known as Schwartze sign, may be visible through a sufficiently transparent
tympanic membrane. If the abnormal bone remodeling extends to the cochlea, sensorineural
hearing loss may also develop. Due to the frequent absence of otoscopic abnormalities and the
potential severity of hearing impairment, otosclerosis is often described with the phrase, "The
doctor sees nothing, and the patient hears nothing."
Etiology
The exact cause of otosclerosis remains uncertain, but several contributing factors have
been proposed:
Genetic Factors
Multiple genetic loci have been associated with otosclerosis, including regions on
chromosomes 6p, 9p, 1q, 3q, 6q, 7q, 15q, and 16q. A genome-wide analysis has also identified a
novel locus on chromosome 7q22.1. Other genetic conditions related to bone metabolism, such
as osteogenesis imperfecta, and genes involved in bone remodeling, including COL1A1, BMP2,
BMP4, AGT, and ACE, have been investigated as potential contributors. Additionally, immune-
related mechanisms, including human leukocyte antigen variations, inflammatory cytokines,
and oxidative stress, have been explored as possible factors.
Hereditary Influence
More than half of individuals diagnosed with otosclerosis have a family history of the
condition. Patients with affected relatives tend to develop symptoms at an earlier age. The
disease is generally inherited in an autosomal dominant pattern with reduced penetrance of
approximately 40% and variable expressivity.
Pregnancy
Hearing loss due to otosclerosis often worsens during pregnancy, though the precise link
between hormonal changes and disease progression remains unclear.
Viral Infections
Measles virus infection has been hypothesized as a potential factor in the development of
otosclerosis. Electron microscopy and immunohistochemical studies have detected measles
virus RNA in the stapes footplate of a majority of affected individuals. Additionally, measles
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vaccination appears to have a protective effect, as studies have reported lower rates of
otosclerosis-related treatment in vaccinated populations.
Other Contributing Factors
Additional triggers, including menopause, trauma, and major surgical procedures, have
been reported as possible causes or aggravating factors for otosclerosis.
Epidemiology
The prevalence of clinical otosclerosis is estimated at 0.04% to 1% among White
individuals, though histological evidence of otosclerosis—without clinical symptoms—has
been detected in up to 10% of this population. In contrast, histological otosclerosis occurs in
approximately 1% of Black individuals and 5% of Asian individuals.
Otosclerosis is an early adult-onset condition, with a higher incidence in women, typically
in a 2:1 ratio compared to men. The disease often begins in the third or fourth decade of life,
though significant hearing loss usually does not manifest until after the fourth decade. Overall,
otosclerosis accounts for 5% to 9% of all cases of hearing loss and is responsible for 18% to
22% of conductive hearing loss cases.
Pathophysiology
Multiple etiological factors, including otosclerosis, are believed to contribute to the
development of bony dyscrasias. The disease process involves abnormal bone remodeling
within the otic capsule, where bone resorption is followed by bone deposition, replacing normal
bone with spongiotic bone. While similar remodeling occurs in other bones, it is not typically
observed in the otic capsule.
In the early stages, osteoclasts become active at the site of the lesion, leading to the
replacement of normal bone with connective tissue. Over time, dense sclerotic bone forms in
areas of previous bone resorption, resulting in disorganized bone structure, increased
osteocytes, and widened marrow spaces filled with vascular and connective tissue. As the
disease progresses, these marrow spaces are eventually replaced by dense, irregularly
structured sclerotic bone.
The initial lesion commonly develops in the fissula ante fenestram, a region between the
oval window and the cochleariform process of the middle ear, and expands via vascular
channels. The reason why this specific area serves as the focal point of otosclerosis remains
unclear, though some researchers suggest that persistent embryonic cartilage remnants in this
location may play a role. In most cases, the lesions remain confined to the anterior oval window
and impair its function by calcifying the annular ligament or affecting the stapes footplate. Both
mechanisms contribute to conductive hearing loss by restricting the stapes' ability to transmit
sound vibrations.
Histopathology
On gross examination, otosclerotic foci appear chalky white, grayish, or yellowish. If the
disease is active and progressing rapidly, the affected areas may appear red due to increased
vascularity, a phenomenon known as the Schwartze sign.
Microscopically, the normally dense enchondral layer of the otic capsule contains spongy
bone in otosclerosis. In early active lesions, there are abundant marrow and vascular spaces
with numerous osteoblasts and osteoclasts. Additionally, a large quantity of cement-like
material appears bluish-gray on hematoxylin and eosin staining, forming what is known as the
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blue mantles of Manasse. As the disease matures, vascularity decreases, and the bone becomes
more fibrotic and sclerotic, staining red with histological dyes.
History and Physical Examination
The most common presenting symptom in patients with otosclerosis is progressive
hearing loss, though tinnitus and, in some cases, vertigo may also be reported. The condition
typically affects both ears, with approximately 70% of patients experiencing bilateral hearing
loss that gradually worsens over time. The hearing loss usually begins in one ear and eventually
progresses to the other.
Early symptoms often include difficulty perceiving low-frequency sounds, such as
whispers. Interestingly, many patients paradoxically report better hearing in noisy
environments, a phenomenon known as paracusis Willisii or paracusis of Willis, first described
in 1672 by Dr. Thomas Willis. While not exclusive to otosclerosis, this finding is indicative of
conductive hearing loss. Tinnitus may become more pronounced as the disease advances, and
although vertigo is usually mild, some patients experience worsening balance, resembling
Ménière’s disease
.
During physical examination, patients with otosclerosis may speak in a low-volume and
monotonous voice due to the nature of their hearing loss. Otoscopic examination often reveals
no visible abnormalities. However, in cases of active otosclerosis, increased vascularity of the
cochlear promontory may be seen through the tympanic membrane, a characteristic finding
known as the Schwartze sign. This sign, however, is relatively uncommon, appearing in only
about 10% of affected individuals.
Evaluation
Tuning Fork Testing
A Weber test using a 512 Hz tuning fork typically lateralizes toward the ear with
conductive hearing loss or the ear with the more significant conductive loss in bilateral
otosclerosis. In the Rinne test, bone conduction is found to be better than air conduction, with
a sensitivity exceeding 90% when the conductive hearing loss surpasses 30 dB. A hearing loss
of this magnitude is generally considered the threshold for surgical intervention.
Audiometry and Tympanometry
In most cases of otosclerosis, pure tone audiometry reveals a decline in low-frequency air
conduction thresholds, while bone conduction remains intact. A Carhart notch is a common
audiometric finding, characterized by an artifactual dip of 20–30 dB at 2000 Hz in the bone
conduction curve, caused by the resonance frequency of the ossicular chain. This notch typically
resolves following stapedectomy. Similar findings may also occur in cases of incus or malleus
fixation and incudostapedial joint detachment.
Mixed hearing loss is observed in advanced otosclerosis when the disease affects the
cochlear endosteum, leading to sensorineural hearing loss, particularly at higher frequencies.
Speech discrimination scores and tympanometry remain normal in early-stage
otosclerosis, with a type A tympanogram. In more advanced cases, tympanometry may show a
flattened or stiffened compliance curve (type As tympanogram), reflecting reduced mobility of
the ossicular chain and tympanic membrane. Tympanometry also aids in differentiating
otosclerosis from other conditions with low resonance, such as ossicular chain discontinuity.
High-Resolution Computed Tomography
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Non-contrast, high-resolution CT of the temporal bones is considered the gold standard
for confirming the diagnosis of otosclerosis. In advanced cases, spongiotic or sclerotic bone
changes are often visible anterior to the oval window. The extent of stapes footplate thickening
and round window involvement plays a crucial role in preoperative planning.
In cochlear otosclerosis, a halo sign may be observed, where radiolucent foci extend from
the fissula ante fenestram and surround the cochlea.
Treatment and Management
Medical Management
Medical treatment primarily aims to halt disease progression rather than cure
otosclerosis. Currently, no medical therapy is definitively curative.
Sodium fluoride has been historically prescribed to slow disease progression, but its
effectiveness remains controversial. Bisphosphonates, which induce osteoclast apoptosis and
inhibit bone resorption, have shown promising results in managing otosclerosis. However,
these medications should not be used during pregnancy due to potential risks.
Third-generation bisphosphonates, including risedronate and zoledronate, as well as
older agents like etidronate, have demonstrated potential benefits in treating otosclerosis.
Newer bisphosphonates appear to be more effective due to their higher potency and lower
incidence of side effects.
Some studies have also suggested that vitamin D and bioflavonoids may contribute to
hearing improvement in certain cases, though results have been inconsistent.
For many patients, bilateral hearing aids are an essential part of treatment, either as a
standalone therapy or in conjunction with other interventions.
Surgical Management
The preferred surgical treatment for otosclerosis is stapedotomy or stapedectomy, both
of which involve the placement of a prosthesis to restore sound transmission. In stapedotomy,
a hole is created in the center of the stapes footplate using either a high-speed microdrill or a
laser, through which a prosthesis is inserted between the long process of the incus and the oval
window membrane. In stapedectomy, the stapes footplate is partially or completely removed,
and a prosthesis is placed between the incus and oval window, typically using a vein or fascia
graft to protect the oval window membrane. In both procedures, the crura of the stapes are
fractured, and the incudostapedial joint is divided to facilitate removal of the stapes
superstructure.
Surgical intervention for otosclerosis generally produces favorable outcomes, provided
that patient selection is appropriate. In patients with bilateral otosclerosis, the ear with the
greater hearing loss is typically operated on first. Performing surgery on both ears during the
same procedure is avoided to prevent the rare but serious risk of bilateral sensorineural
hearing loss following surgery. A 2018 review by Cheng et al reported that stapedotomy and
stapedectomy yield comparable results, though stapedotomy demonstrated a slight advantage
in terms of high-frequency hearing preservation and reduced complication rates.
If the initial surgery does not sufficiently improve hearing, revision surgery may be
considered, though success rates vary. In some cases, even after surgery, hearing aid use may
still be required if the outcome is suboptimal.
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