Bony Otic Capsule Research Articles

Three-dimensionally visualized ossification and mineralization process of the otic capsule in a postnatal developmental mouse.

We aimed to elucidate the ossification process of the otic capsule in postnatal C57BL/6 mice and depict the three-dimensional (3D) process of otoconial mineralization in vivo. The otic capsules of C57BL/6 mice were stained with alizarin red and imaged/compared using micro-computed tomography on postnatal day (P) between P0 and P8, P10, P15, and P30 and 3-4 months old (P3-4Mo). We reconstructed 3D images of the otic capsule and otoconia and measured the bone mineral density using x-ray absorptiometry on each age. The 3D reconstructed otic capsule images revealed two ossification centers of the otic capsule at P0. One was observed around the ampulla of the superior semicircular canal and utricle, and the other was observed around the ampulla of the posterior semicircular canal. The cross-sectional views demonstrated that modiolar ossification developed from the base to the apex from P4 to P8. The inter-scalar septum ossified bidirectionally from the modiolus and bony otic capsule from P8 to P15. The mineralized otoconia were first detected in the utricle at P3 and saccular otoconia at P6. The density of the utricle and saccular otoconia showed different growth trends. To the best of our knowledge, this is the first study to demonstrate the 3D appearance of the otic capsule and otoconia in different developmental stages of mice. We also revealed that modiolar and inter-scalar septal calcification is the final event in the cochlea and that it can be susceptible to pathological conditions (cochlear congenital malformations and hereditary vestibular diseases). The unique features of the ossification process and duration may explain these pathological conditions observed in humans. 3.

The Spatial Distribution of Cellular Voids in the Human Otic Capsule: An Unbiased Quantification of Osteocyte-Depleted Areas.

This study aimed to describe the spatial distribution of osteocyte-depleted areas, so-called cellular voids, in the human otic capsule and compare it with that of otosclerosis. Systematic histological studies of the bony otic capsule have revealed an osteoprotegerin (OPG)-mediated inhibition of normal bone remodeling around the inner ear. The resulting accumulation of bony degeneration and dead osteocytes has been thoroughly documented, and the spatial distribution of dead osteocytes and matrix microcracks resembles that of the human ear disease otosclerosis. Clusters of dead osteocytes that may interfere with osteocyte connectivity and thereby the OPG signaling pathway have been described in human temporal bones. It is possible that these cellular voids create disruptions in the antiresorptive OPG signal that may give rise to local pathological remodeling. Recently, a method of detecting cellular voids was developed. This study uses unbiased stereology to document the spatial distribution of cellular voids in bulk-stained undecalcified human temporal bone. Cellular voids accumulate around the inner ear and increase in number and size with age. Furthermore, cellular voids are more frequently found in the anterior and lateral regions of the otic capsule, which are known predilection sites of otosclerosis. This colocalization of cellular voids and otosclerosis suggests a causal relationship between focal degeneration and otosclerotic remodeling.

Hearing impairment in murine model of Down syndrome.

Hearing impairment is a cardinal feature of Down syndrome (DS), but its clinical manifestations have been attributed to multiple factors. Murine models could provide mechanistic insights on various causes of hearing loss in DS. To investigate mechanisms of hearing loss in DS in the absence of the cadherin 23 mutation, we backcrossed our DS mice, Dp(16)1Yey, onto normal-hearing CBA/J mice and evaluated their auditory function. Body weights of wild type (WT) and DS mice were similar at 3-months of age, but at 9-months, WT weighed 30% more than DS mice. Distortion product otoacoustic emissions (DPOAE), a test of sensory outer hair cell (OHC) function negatively impacted by conductive hearing loss, were reduced in amplitude and sensitivity across all frequencies in DS mice. The middle ear space in DS mice appeared normal with no evidence of infection. MicroCT structural imaging of DS temporal bones revealed a smaller tympanic membrane diameter, oval window, and middle ear space and localized thickening of the bony otic capsule, but no gross abnormalities of the middle ear ossicles. Histological analysis of the cochlear and vestibular sensory epithelium revealed a normal density of cochlear and vestibular hair cells; however, the cochlear basal membrane was approximately 0.6 mm shorter in DS than WT mice so that the total number of hair cells was greater in WT than DS mice. In DS mice, the early and late peaks in the auditory brainstem response (ABR), reflecting neural responses from the cochlear auditory nerve followed by subsequent neural centers in the brainstem, were reduced in amplitude and ABR thresholds were elevated to a similar degree across all frequencies, consistent with a conductive hearing impairment. The latency of the peaks in the ABR waveform were longer in DS than WT mice when compared at the same intensity; however, the latency delays disappeared when the data were compared at the same intensity above thresholds to compensate for the conductive hearing loss. Future studies using wideband tympanometry and absorbance together with detailed histological analysis of the middle ear could illuminate the nature of the conductive hearing impairment in DS mice.

Distribution of microcrack surface density in the human otic capsule

Background The bony otic capsule is comprised of highly mineralized and dense compact bone. It is rarely remodelled and degenerative changes, therefore, accumulate around the inner ear. It is also a predilection site for the pathological remodelling seen in otosclerosis. Morphometric studies have documented increased numbers of dead osteocytes and microcracks in the human otic capsule. Microcracks may disrupt the lacuno-canalicular network and cause osteocyte apoptosis ultimately breaking up the perilabyrinthine bone signalling pathways and dynamics. This may be important to understand the pathogenesis of remodelling diseases like otosclerosis. Aims/Objectives This study describes the spatial and regional distribution of microcrack surface density in relation to the inner ear and compares it to that previously recorded for otosclerosis. Material and methods Forty-two temporal bones and five ribs were used. All samples were undecalcified, bulk stained in basic fuchsin and plastic embedded. Unbiased stereology was used to estimate the true surface density of microcracks (mm2/mm3) in perilabyrinthine bone. Results The surface density of microcracks accumulates around the inner ear spaces, particularly in the lateral window regions, and increases with age. Conclusions and significance This study documents the spatial and temporal association between microfractures and otosclerosis in the otic capsule.

Audiovestibular Quantification in Rare Third Window Disorders in Children.

Third window disorders are structural abnormalities in the bony otic capsule that establish a connection between the middle/inner ear or the inner ear/cranial cavity. Investigated extensively in adults, they have hardly been studied in children. This study is a retrospective study of children (aged 5–17 years) diagnosed with rare third window disorders (third window disorders reported rarely or not reported in children) in a tertiary pediatric vestibular unit in the United Kingdom. It aimed to investigate audiovestibular function in these children. Final diagnosis was achieved by high resolution CT scan of the temporal bones. Of 920 children attending for audiovestibular assessment over a 42 month period, rare third windows were observed in 8 (<1%). These included posterior semicircular canal dehiscence (n = 3, 0.3%), posterior semicircular canal thinning (n = 2, 0.2%), X linked gusher (n = 2, 0.2%), and a combination of dilated internal auditory meatus/irregular cochlear partition/deficient facial nerve canal (n = 1, 0.1%). The majority of them (87.5%) demonstrated a mixed/conductive hearing loss with an air-bone gap in the presence of normal tympanometry (100%). Transient otoacoustic emissions were absent with a simultaneous cochlear pathology in 50% of the cohort. Features of disequilibrium were observed in 75% and about a third showed deranged vestibular function tests. Video head impulse test abnormalities were detected in 50% localizing to the side of the lesion. Cervical vestibular evoked myogenic potential test abnormalities were observed in all children in the cohort undergoing the test where low thresholds and high amplitudes classically found in third window disorders localized to the side of the defects in 28.5%. In the series, 71.4% also demonstrated absent responses/amplitude asymmetry, some of which did not localize to the ipsilesional side. Two children presented with typical third window symptoms. This study observes 2 new rare pediatric third window phenotypes and the presence of a cochlear hearing loss in these disorders. It emphasizes that these disorders should be considered as an etiology of hearing loss/disequilibrium in children. It also suggests that pediatric third window disorders may not present with classical third window features and are variable in their presentations/audiovestibular functions.

Dynamic characteristics of the middle ear after stapes surgery: a distortion product otoacoustic emission study

BackgroundOtosclerosis is a primary localized disease of the bony otic capsule that is mainly localized to the stapedial footplate. Stapedotomy is the treatment of choice. The effect of stapes surgery on otoacoustic emissions is not sufficiently known.ObjectivesThe aim of the present study was to assess changes in the middle ear dynamic characteristics, and to evaluate distortion product otoacoustic emissions (DPOAEs) in otosclerosis. Moreover, the study aimed to evaluate DPOAEs before and after stapes surgery.Patients and methodsA total of 20 patients with otosclerosis and undergoing stapedotomy surgery were included in the study. Assessment was performed preoperatively, 1 week, 1 month, and 6 months postoperatively by using pure-tone average, tympanometry, and DPOAE.ResultsSignificant improvement in the air–bone gap by pure-tone average was reported at 1 week and 1 month postoperatively, whereas 6 months postoperative hearing threshold remained the same as that of 1 month postoperative. The difference between preoperative and postoperative detection of DPOAE was not significant.ConclusionConventional pure-tone audiometry remains the choice for evaluation of stapes surgery in patients of otosclerosis. The use of DPOAEs in the evaluation of a successful stapes surgery requires further studies including a larger number of patients.

Thickness of the Bony Otic Capsule: Etiopathogenetic Perspectives on Superior Canal Dehiscence Syndrome

The etiology of superior canal dehiscence (SCD) is controversial. An embryological perspective suggests that SCD may occur through the failure of postnatal bone formation over the superior semicircular canal (SC), whereas an acquired theory suggests that trauma or pressure from the overlying temporal lobe could break or gradually thin the SC. We infer the etiology of SCD by comparing the thickness of the bony otic capsule of the unaffected side of SCD patients with that of non-SCD participants. Twelve SCD patients (13 SCD ears and 11 normal ears) and 34 age-matched controls (68 ears) were included. The control group was subdivided into an aerated group (49 ears) and a nonaerated group (19 ears), as defined by the presence of air cells above the SC. A high-resolution temporal bone CT was performed in all participants. The thicknesses of the SC, horizontal canal (HC) and posterior canal (PC) of the unaffected ears of SCD patients were compared with those of the controls. The SC of the unaffected side in the SCD group (n = 11, 0.41 ± 0.23 mm) was significantly thinner than the one in the control group (n = 68, 0.64 ± 0.21 mm, p = 0.002). The HC and PC were also thinner in the SCD group (n = 24, 0.58 ± 0.11 and 1.39 ± 0.31 mm, respectively) than in the controls (0.70 ± 0.08 and 1.61 ± 0.32 mm; p < 0.0001 and p = 0.005, respectively). The SC, HC and PC thicknesses were also compared between the aerated and nonaerated ears within the control group. The SC was significantly thicker in the aerated group (0.73 ± 0.14 mm) than in the nonaerated group (0.60 ± 0.23 mm; p = 0.046); however, no significant difference was observed for the HC and PC thickness (aerated group, n = 49, 0.72 ± 0.07 and 1.67 ± 0.34 mm; nonaerated group, n = 19, 0.70 ± 0.09 and 1.59 ± 0.34 mm; p = 0.350 and p = 0.428, respectively). The bony otic capsule was significantly thinner in the SCD patients than in the controls. However, even within unaffected individuals, SCs lacking overlying air cells were also thinner than those with overlying air cells. These results suggest that both embryological and acquired factors affect the occurrence of SCD.

Quantitative polarized light microscopy of human cochlear sections.

Dysfunction of the inner ear is the most common cause of sensorineural hearing loss, which is the most common sensory deficit worldwide. Conventional imaging modalities are unable to depict the microanatomy of the human inner ear, hence the need to explore novel imaging modalities. We provide the first characterization of the polarization dependent optical properties of human cochlear sections using quantitative polarized light microscopy (qPLM). Eight pediatric cadaveric cochlear sections, aged 0 (term) to 24 months, were selected from the US National Temporal Bone Registry, imaged with qPLM and analyzed using Image J. Retardance of the bony otic capsule and basilar membrane were substantially higher than that of the stria vascularis, spiral ganglion neurons, organ of Corti and spiral ligament across the half turns of the spiraling cochlea. qPLM provides quantitative information about the human inner ear, and awaits future exploration in vivo.

Prolactin Expression in the Cochlea of Aged BALB/c Mice Is Gender Biased and Correlates to Loss of Bone Mineral Density and Hearing Loss

Prolactin is a versatile hormone with over 300 known functions and predominantly expressed in the pituitary. However, its expression has additionally been found in a number of extrapituitary organs. Recently, we described the expression of prolactin in the inner ear of mice, where it was correlated to age. Previous research has shown prolactin to be linked to abnormal bone metabolism and hearing loss due to changes in morphology of the bony otic capsule. Here we further investigated the relationship between prolactin, hearing loss and cochlea bone metabolism. BALB/c mice were tested for hearing using ABR at 6 and 12 months of age. Bone mineral density of the cochlea was evaluated using microCT scanning. Prolactin expression was calculated using quantitative real time PCR. Expression of the key regulators of bone metabolism, osteoprotegerin and receptor activator of nuclear factor-kappaB ligand were also determined. We found that prolactin expression was exclusive to the female mice. This also correlated to a greater threshold shift in hearing for the females between 6 and 12 months of age. Analyses of the cochlea also show that the bone mineral density was lower in females compared to males. However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found. Further analysis of cochlea histological sections revealed larger ostocyte lacunae in the females. These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops. In addition, it has the potential to lead to treatment for this specific type of hearing loss.

Otosclerosis: A perilabyrinthine threshold phenomenon

This paper is a review of our most recent findings concerning the osteo-dynamics of the bony otic capsule and pathogenesis of otosclerosis. By exploring the spatial relationship between normal perilabyrinthine bone remodeling, the viability and spatial distribution of labyrinthine osteocytes, and the location of otosclerosis, a unique spatial pattern emerged. Bone remodeling is highly inhibited around the inner ear space. Most likely, inner ear anti-resorptive signals enter the bony otic capsule through the lacuno-canalicular porosity. The patency of this signaling pathway depends on the viability of individual osteocytes. In the young otic capsule the density of viable osteocytes is high and centripetally distributed. This arrangement may sustain a life-long osseus pathway for anti-resorptive signals even within a bone where a considerable loss of viable osteocytes must be expected, as demonstrated by a centripetal accumulation of dead osteocytes with age. The spatial distribution of dead osteocytes follows the same general pattern as otosclerosis. We suggest that clustering of dead osteocytes may impede the transmission of anti-resorptive signals locally, leaving such ghost regions susceptible to focal bone remodeling as in human otosclerosis. The preserved network of viable osteocytes around the depleted ghost regions may contain the process and distort the structure of bone remodeling into an abnormal otosclerotic pattern.

The viability and spatial distribution of osteocytes in the human labyrinthine capsule: A quantitative study using vector-based stereology

Background Bone remodeling is highly inhibited around the labyrinthine space, most likely by the action of the anti-resorptive cytokine osteoprotegerin (OPG). Inner ear OPG may enter the bony otic capsule through the lacuno-canalicular porosity (LCP). The aim of the study was to investigate the patency of this extracellular signaling pathway by exploring the viability, age dependency and spatial distribution of capsular osteocytes. Methods Sixty-five bulk-stained undecalcified human temporal bones were selected to span the ages from 30th gestational week to 95 years. Osteocytes within 1000 μm wide iso-concentric perilabyrinthine zones of bone were identified by 3-D vector calculations and the number of cells per unit of bone volume estimated within each zone by optical dissectors. Results From a high initial numerical density and a centripetal distribution of viable osteocytes, the density declined over time. This effect was higher towards the inner ear space and shifted viable osteocytes into to a centrifugal distribution with age. Contrary to this, non-viable osteocytes accumulated centripetally around the inner ear space and accounted for 50% of all lacunae at 80 years of age. Non-viable osteocytes were heterogeneously distributed forming islets of varying size surrounded by the intact and viable parts of the LCP. Conclusion The simultaneous presence of high numbers of non-viable osteocytes within a dense network of viable osteocytes is unique for the bony otic capsule. Viable osteocytes may sustain a life-long anti-resorptive signaling pathway for inner ear OPG. Clustering of non-viable osteocytes may locally impede the effect of OPG leaving the ghost regions unprotected against focal bone remodeling, as in human otosclerosis.

Entry of Substances Into Perilymph Through the Bone of the Otic Capsule After Intratympanic Applications in Guinea Pigs

Drugs applied to the middle ear enter perilymph through the bony otic capsule. Drugs applied intratympanically in humans are thought to enter the cochlea primarily through the round window membrane (RWM). Local drug treatments of the ear are commonly evaluated in rodent models. The otic capsule is much thinner at the cochlear apex in rodents than in humans. We therefore investigated whether drugs applied to the middle ear could enter perilymph through the otic capsule as well as through the RWM. The distribution of gentamicin and the marker trimethylphenylammonium (TMPA) along the guinea pig cochlea was assessed with sequential apical perilymph sampling after 2 delivery paradigms that included 1) completely filling the tympanic bulla with solution and 2) applying the solution to the RWM only. In addition, TMPA entry into perilymph of the third turn was measured with ion-selective electrodes after the bulla was filled with TMPA solution. In application protocols that allowed drug to contact the otic capsule (by completely filling the bulla), markedly higher drug concentrations were found in the apical, low-frequency regions of the cochlea compared with drug applications to the RWM only. Gentamicin and TMPA can enter perilymph of guinea pigs through the RWM and simultaneously through the bony otic capsule. Drug distribution along the cochlea after intratympanic applications will therefore be dramatically different in rodents and humans. Results obtained from intratympanic drug treatments of animals, in which the bulla is filled with solution and contacts the bony capsule of the cochlea, do not provide a good model for the situation in humans.

Darstellung cochleärer Binnenstrukturen durch Optische Kohärenz-Tomografie (OCT)

Optical Coherence Tomography (OCT) is a relatively new imaging technique, which provides scans similar to sonography on an optical base. We questioned whether OCT may be helpful in optimizing anatomical orientation in cochlear implant (CI) surgery. In a study on temporal bone specimens we tested, whether OCT provides information about the cochlear topography, particularly in situations, when for cochleostomy the bony otic capsule is already opened but the membranous endosteal layer is still intact. OCT was performed on five human temporal bone preparations, in which the cochleostomy was carried out still leaving the endosteum covering the fluid-filled inner ear intact. A prototype of operating microscope was used, in which a spectral-domain OCT (SD-OCT) with a central wavelength of 840 nm was integrated. On all scans, OCT supplies information about inner ear structures, such as the lateral attachment of the basilar membrane dividing the scalae. Even delicate structures like the Reissner's membrane could be identified in one case. This pilot study clearly documents the possibility to identify inner ear structures, especially the site of the scala tympani while its enveloping membranes are still intact. These findings may have an impact on cochlear implant surgery, especially as an orientation guide to localize the scala tympani precisely before opening the fluid-filled inner ear.

A new classification for cochleovestibular malformations.

The report proposes a new classification system for inner ear malformations, based on radiological features of inner ear malformations reviewed in 23 patients. The investigation took the form of a retrospective review of computerized tomography findings relating to the temporal bone in 23 patients (13 male and 10 female patients) with inner ear malformations. The subjects were patients with profound bilateral sensorineural hearing loss who had all had high-resolution computed tomography (CT) with contiguous 1-mm-thick images obtained through the petrous bone in axial sections. The CT results were reviewed for malformations of bony otic capsule under the following subgroups: cochlear, vestibular, semicircular canal, internal auditory canal (IAC), and vestibular and cochlear aqueduct malformations. Cochlear malformations were classified as Michel deformity, common cavity deformity, cochlear aplasia, hypoplastic cochlea, incomplete partition types I (IP-I) and II (IP-II) (Mondini deformity). Incomplete partition type I (cystic cochleovestibular malformation) is defined as a malformation in which the cochlea lacks the entire modiolus and cribriform area, resulting in a cystic appearance, and there is an accompanying large cystic vestibule. In IP-II (the Mondini deformity), there is a cochlea consisting of 1.5 turns (in which the middle and apical turns coalesce to form a cystic apex) accompanied by a dilated vestibule and enlarged vestibular aqueduct. Four patients demonstrated anomalies involving only one inner ear component. All the remaining patients had diseases or conditions affecting more than one inner ear component. Eight ears had IP-I, and 10 patients had IP-II. Ears with IP-I had large cystic vestibules, whereas the amount of dilation was minimal in patients with IP-II. The majority of the semicircular canals (67%) were normal. Semicircular canal aplasia accompanied cases of Michel deformity, cochlear hypoplasia, and common cavity. In 14 ears, the IAC had a defective fundus at the lateral end. In two ears the IAC was absent. In all seven cases of common cavity malformations, there was a bony defect at the lateral end of the IAC. In five of them the IAC was enlarged, whereas in two the IAC was narrow. All patients with IP-I had an enlarged IAC, whereas in patients with type II disease, four had a normal IAC and 10 had an enlarged IAC. All cases of IP-II had an enlarged vestibular aqueduct, whereas this finding was not present in any of the cases of IP-I. In all cases, the vestibular aqueduct findings were symmetrical on both sides (simultaneously normal or enlarged). No patient demonstrated enlargement or any other abnormalities involving the cochlear aqueduct. Radiological findings of congenital malformations in the present study suggested two different types of incomplete partition. Cystic cochleovestibular malformation (IP-I) and the classic Mondini deformity (IP-II). The type I malformation is less differentiated than the type II malformation. Classic Mondini deformity has three components (a cystic apex, dilated vestibule, and large vestibular aqueduct), whereas type I malformation has an empty, cystic cochlea and vestibule without an enlarged vestibular aqueduct. Mondini deformity represents a later malformation, so the amount of dysplasia is much less than in type II. Therefore, it is more accurate and useful for clinical purposes to classify these malformations (in descending order of severity) as follows: Michel deformity, cochlear aplasia, common cavity, IP-I (cystic cochleovestibular malformation), cochlear hypoplasia, and IP-II (Mondini deformity). Only in this way can these complex malformations be grouped precisely and the results of cochlear implantation compared.

Quantification of solute entry into cochlear perilymph through the round window membrane

The administration of drugs to the inner ear via the round window membrane is becoming more widely used for both clinical and experimental purposes. The actual drug levels achieved in different regions of the inner ear by this method have not been established. The present study has made use of simulations of solute movements in the cochlear fluids to describe the distribution of a marker solute in the guinea pig cochlear fluid spaces. Simulation parameters were derived from experimental measurements using a marker ion, trimethylphenylammonium (TMPA). The distribution of this ion in the cochlea was monitored without volume disturbance using TMPA-selective microelectrodes sealed into the first and second turns of scala tympani (ST). TMPA was applied to perilymph by irrigation of the intact round window membrane with 2 mM solution. At the end of a 90 min application period, TMPA in the first turn, 1.4 mm from the base of ST, reached an average concentration of 330 μM (standard deviation (S.D.) 147 μM, n=8). TMPA in the second turn, 7.5 mm from the base of ST reached a concentration of 15 μM (S.D. 33 μM, n=5). The measured time courses of TMPA concentration change were interpreted using the Washington University Cochlear Fluids Simulator (V 1.4), a public-domain program available on the internet at http://oto.wustl.edu/cochlea/. Simulations with parameters producing concentration time courses comparable to those measured were: (1) round window permeability: 1.9×10 −8 cm/s; (2) ST clearance half-time: 60 min; (3) longitudinal perilymph flow rate: 4.4 nl/min, directed from base to apex. Solute concentrations in apical regions of the cochlea were found to be determined primarily by the rate at which the solute diffuses, balanced by the rate of clearance of the solute from perilymph. Longitudinal perilymph flow was not an important factor in solute distribution unless the bony otic capsule was perforated, which rapidly caused substantial changes to solute distribution. This study demonstrates the basic processes by which substances are distributed in the cochlea and provides a foundation to understand how other applied substances will be distributed in the ear.

Quantification of Osteoclastic Resorption of the Bovine Otic Capsule in vitro by an Enzyme-Linked Immunosorbent Assay

The bony shell surrounding the inner ear is known to have a very pronounced centripetal inhibition of remodelling in vivo, with almost no bone turnover immediately adjacent to the perilymphatic spaces and a gradually increasing turnover rate towards outer parts of the bony otic capsule. By the use of in vitro markers of bone resorption, including an enzyme-linked immunosorbent assay for quantification of type I collagen degradation and a colorimetric enzyme assay for quantification of osteoclast tartrate-resistant acid phosphatase activity, this study demonstrates that there are no ex vivo differences in bone matrix resorption between the inner and outer parts of the otic capsule when exposed to seeded osteoclasts from rabbits. Thus, the unique spatial distribution of perilabyrinthine bone turnover is not caused by a shift in resorbability from inner to outer capsular bone that is due to inherent bone quality differences particular to these bone compartments. More likely, the sustained action of some intravital ‘field force’, originating from the inner ear spaces, is responsible for the unique spatial distribution of the otic capsular bone turnover found in vivo. Though the character of this force is not yet defined, it is appealing to relate it to the large electromagnetic potential gradient present in the inner ear.

Volume-Referent Bone Turnover Estimated From the Interlabel Area Fraction After Sequential Labeling

In the compact bony otic capsule remodeling is low, and bone remodeling units are distributed centrifugally in relation to inner ear tissues and spaces. Fluorochrome-labeled bone remodeling units are scarce, abortive, and tortuous with no uniform direction of movement. This study presents a method for the estimation of volume-referent bone turnover based on measurements of the fractional area between labels after sequential labeling with osteofluorochromes. The applicability of this method is tested against a classical quantification method in undecalcified cortical specimens from the canine humerus, where both methods can be used. The estimate of bone turnover derived from the new sequential labeling in eight dogs is 7.4% (SEM 2.1%) per year and the classic estimate derived from calculations of the formative osteonal area and the formative period yields 6.9% (SEM 2.1%) per year. Agreement is sufficient to justify future measurements of absolute bone turnover in sequentially labeled perilabyrinthine bone.

Temporal Bone Dynamics, The Hard Way: Formation, Growth, Modeling, Repair and Quantum Type bone remodeling in the Otic Capsule

This review presents studies in which temporal bone dynamics were monitored in undecalcified human and animal materials by combined microradiography and osteofluorochromic time labeling. The results are interpreted in accordance with modern concepts of spatial and temporal organization of bone behavior in an attempt to contribute to a new basis for understanding the structure and function of the bony otic capsule. In postcartilaginous development, perilabyrinthine bone formed a separate functional unit in which growth and modeling were absent. Consequently, all drift movements bypassed the bone present inside a narrow perilabyrinthine zone, which in effect maintained a so-called drift barrier enclosing the entire inner ear. In baseline bone remodeling and repair-associated remodeling transients, secondary osteons were distributed centrifugally with respect to inner ear spaces, and the average osteonal size decreased towards the inner ear, suggesting a progressive inhibition of bone resorption towards inner ear spaces. No histological capsular component proved resistant to bone resorption during modeling and remodeling. Instead the dynamic behaviour of any moiety of capsular bone appeared to depend on its spatial relation to the membranous labyrinth rather than on histological characteristics. This spatial organization of perilabyrinthine bone development and turnover is responsible for the unique histology of capsular bone and may explain the accumulation of fatigue micro-cracks which can be found in human perila byrinthine bone. These findings suggests the role of inner ear tissues as a functional matrix in control of capsular bone dynamics even beyond fetal life.

Inner ear pathology in the Palmerston North autoimmune strain mouse

The Palmerston North autoimmune strain mouse is a model for spontaneous systemic lupus erythematosus. Inner ear structure and function were examined during the onset and progression of systemic autoimmune disease to identify potentially correlated auditory system pathology. The onset of systemic disease occurred at 4 to 5 months of age and was characterized by elevated serum immune complexes, cryoglobulins, and antinuclear antibodies. Coincident with the onset of autoimmune disease was degeneration of the apical turn stria vascularis and outer hair cells. These cochlear changes progressed basal-ward. At 10 months of age, auditory brainstem response thresholds were elevated and the stria vascularis area was measurably smaller throughout the cochlea. Immunohistochemical staining showed immunoglobulin G deposits within the organ of Corti, the vas spirale of the basilar membrane, the scala tympani, and marrow cavities of the bony otic capsule. These results suggest that cochlear pathology may be immune mediated in this mouse, which would make the strain suitable for the study of the mechanisms relating inner ear abnormalities and autoimmune disease.

Remodeling Patterns in the Bony Otic Capsule of the Dog

Quantum-type bone remodeling was studied in undecalcified temporal bones and long bone specimens from adult mongrel dogs by means of combined microradiography, osteofluorochrome labeling, and osteoid staining. The overall turnover rate of capsular bone was estimated to be low compared to that of extracapsular compact bone. Evolving secondary osteons were distributed centrifugally relative to the perilymphatic space. Moreover, a zone of bone tissue enclosing perilymphatic spaces was found completely devoid of evolving secondary osteons. Throughout the otic capsule, segmentary perivascular foci of resorption and formation were present. These findings indicate that remodeling of capsular bone is subject to sustained local inhibition. The significance of this conclusion is considered with special reference to otosclerosis.