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Background: Otosclerosis is a common ear disease that causes fixation of the stapes and conductive hearing impairment. However, the pathogenesis of otosclerosis is still unknown. Otosclerosis could be associated with the unique bony environment found in the otic capsule. Normal bone remodelling is almost completely absent around the inner ear after birth allowing degenerative changes and dead osteocytes to accumulate. High levels of inner ear anti resorptive osteoprotegerin (OPG) is most likely responsible for this capsular configuration. Studies have demonstrated how osteocyte lifespan variation creates occasional clusters of dead osteocytes, so-called cellular voids, at otosclerotic predilection sites in the human otic capsule. These cellular voids have been suggested as possible starting points of otosclerosis., Aim: To describe the cellular viability in otosclerotic lesions and compare it to that of cellular voids., Materials and Methods: The study was based on unbiased stereological quantifications in undecalcified human temporal bones with otosclerosis., Results: Osteocyte viability was found to vary within the otosclerotic lesions. Furthermore, the results presented here illustrate that inactive otosclerotic lesions consist of mainly dead interstitial bone, much like cellular voids., Conclusions and Significance: Focal degeneration in the otic capsule may play an important role in the pathogenesis of otosclerosis.

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 (mm 2 /mm 3 ) 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.

Conclusion: Current guidelines recommend reporting short-term results of > 12 months after treatment of conductive hearing loss. This study suggests that short-term hearing results after stapedotomy recorded at the 3-month follow-up are without loss of vital information compared with data from the currently recommended > 12-month follow-up. The use of 3-month data in reporting outcome could reduce the bias inherent to the loss to follow-up at 12 months., Objective: To investigate the stability of short-term postoperative hearing after stapedotomy for otosclerosis., Methods: This was a prospective database study; 371 cases with otosclerosis were registered in the database between August 2004 and June 2013. We included the 166 primary cases and 37 revision cases that had attended both follow-ups., Results: The mean changes in postoperative hearing thresholds between the 3-month and 12-month follow-up in both primary and revision cases were minimal and clinically insignificant. In all, 3-5% of primary cases and 14-16% of revision cases experienced a change of ≥ 10 dB for the worse of one or more parameters between follow-ups. Results were also stable when considering a range of traditional success criteria. Other complications following surgery were infrequent and typically resolved long term.

Conclusions: Age-dependent microdamage (MDx) accumulates excessively in human perilabyrinthine bone, where the bone turnover is almost absent. This may have pathological implications for bone-specific disorders such as otosclerosis. The role of MDx accumulation is discussed from an osteodynamic perspective., Objectives: Bone remodelling is highly inhibited within the otic capsule compared with the rest of the skeleton. Consequently excessive accumulation of age-dependent capsular MDx is expected. This study describes the prevalence, size and topographical distribution of MDx in the human otic capsule., Methods: A total of 241 undecalcified human temporal bones were examined. Bulk staining and the cutting-grinding technique were used to separate in vivo MDx from microcrack artefacts induced post mortem by the milling procedure. Quantitative data were obtained by fluorescence microscopy by counting and measuring and by the use of stereology., Results: Microcracks accumulated continuously and extensively in the human otic capsule throughout life. Both the number and total length of MDx were higher close to the inner ear space as compared with the capsular periphery. The mean length of the MDx remained constant with age. There was no statistically significant sex difference.

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.

Conclusion: The endolymphatic sac is part of the membranous inner ear and is thought to play a role in the fluid homeostasis and immune defense of the inner ear; however, the exact function of the endolymphatic sac is not fully known. Many of the detected mRNAs in this study suggest that the endolymphatic sac has multiple and diverse functions in the inner ear., Objectives: The objective of this study was to provide a comprehensive review of the genes expressed in the endolymphatic sac in the rat and perform a functional characterization based on measured mRNA abundance., Methods: Microarray technology was used to investigate the gene expression of the endolymphatic sac with the surrounding dura. Characteristic and novel endolymphatic sac genes were determined by comparing with expressions in pure dura., Results: In all, 463 genes were identified specific for the endolymphatic sac. Functional annotation clustering revealed 29 functional clusters.

Unlabelled: Abstract Conclusion: There is no change in the total cell population and hair cell:supporting cell ratio in the human utricular macula from gestational week 16 and onwards, whereas the lower hair cell:supporting cell ratio and lower total number of cells in the youngest specimens indicate that the utricle is still differentiating and adding new cells at the 10th to 12th gestational week., Objectives: Archival temporal bones were investigated to quantify cell numbers in the utricular macula in fetuses and children., Methods: The age of the subjects ranged from gestational week 10 to 15 years. The optical fractionator was used to estimate the total number of cells in the utricular macula., Results: The total cell number was found to be 143 000 in subjects older than gestational week 16. The number of hair cells and supporting cells did not change between the 16th gestational week and 15 years and was 36 000 and 107 000, respectively. In the youngest specimen (10th and 12th gestational week) there was a statistically significant lower total number of cells (62 000) and a lower hair cell:supporting cell ratio, resulting in a mean number of 13 000 hair cells and 49 000 supporting cells.

Conclusion: This study documents that otosclerotic bone remodeling is distributed centripetally around the inner ear space whereas normal bone remodeling is distributed centrifugally. We suggest that this inverse relation reflects the unique osteo-dynamic setting of the otic capsule: since perilabyrinthine bone remodeling is extremely low, osteocyte deficiency and microcracks accumulate in excess toward the inner ear space with age. This may disrupt the osseus functional network, impede propagation of anti-resorptive signals, and precipitate otosclerotic bone remodeling with a spatial preference for older bone., Objective: To quantify the spatial distribution of otosclerotic bone around the inner ear space in order to explore a possible spatial relation with normal capsular bone remodeling., Methods: Otosclerotic lesions in 53 undecalcified human temporal bones were identified and volume data were measured with the CAST-grid system and processed by dedicated software for advanced design-based stereology., Results: The maximum volume fraction of otosclerotic bone was observed in the innermost perilabyrinthine zones of the otic capsule. The volume fraction of otosclerotic bone declined gradually but significantly from the inner ear space towards the capsular periphery with a general perilabyrinthine centripetal distribution.

Conclusions: The location and three-dimensional (3D) shapes of the otosclerotic foci suggest a general centripetal distribution of otosclerotic bone remodeling around the inner ear space, whereas the normal bone remodeling is distributed centrifugally. The existence of an inverse spatial relation between normal and otosclerotic bone remodeling suggests that inner ear mechanisms in control of bone remodeling may have a pathogenetic role in otosclerosis., Objectives: To explore the 3D shape of otosclerotic lesions around the inner ear space by introducing the use of 3D reconstructions and to discuss the results in a new context of temporal bone dynamics and perilabyrinthine signaling pathways., Methods: Thirty-four otosclerotic lesions from 20 decalcified human temporal bones were rendered and visualized with the public 3D 'Reconstruct' software., Results: The majority of otosclerotic lesions were found close to the labyrinthine space at the well-established topographical sites of predilection with a smooth demarcation against the surrounding bone. However, in addition the virtual 3D technique revealed a new perilabyrinthine anisotropy of individual otosclerotic lesions, displaying a bulky end facing the inner ear space and a volumetric decline towards the capsular periphery.

The repair of 1 mm drill hole lesions in rabbit long bones and otic capsules was studied in undecalcified sections. Following surgery, bone formation was monitored during 12 weeks by intravital sequential time labeling with bone-seeking fluorochromes. In diaphyseal bone, initial repair by trabecular woven bone was accompanied by a transient remodeling response in primary repair bone and the surrounding compacta. In comparison, capsular defects showed a slightly deficient initial repair by woven bone which, once formed, persisted unchanged with no subsequent osteonal remodeling. In the surrounding capsule, the remodeling response was subtle and its duration much shorter. Moreover, the centrifugal distribution of bone remodeling units around inner ear spaces was preserved, suggesting that capsular repair is affected by the same morphogenetic field that controls perilabyrinthine growth, modeling and remodeling. The significance of these findings is briefly discussed in relation to otosclerosis and cochlear implant strategies.

Distribution of bone remodeling units (BRU) in relation to the perilymphatic space was studied in undecalcified temporal bones from adult rabbits labeled in vivo with bone-seeking fluorochromes. Based on recordings of focal bone formation, relative densities of BRUs inside concentric tissue zones around the inner ear spaces were estimated. Zonal densities of BRUs were found to decline towards the perilymphatic space, lending further support to the existence of a local inner ear mechanism in control of capsular bone tissue dynamics. The possible nature of this mechanism is considered briefly with special reference to inner ear electromechanic activity.

Bone modeling determines postuterine gross bone architecture. During growth the shape and proportion of all bones are continuously adapted to function by surface resorption and surface formation. This process is responsible for exchange of most primary endochondral type bone with lamellar endosteal or periosteal bone. By a combination of microradiography, tetracycline fluorescence and osteoid staining of undecalcified material bone modeling in the otic capsule of the rat was studied and compared to well-known modeling patterns in rat long bones. Perilymphatic spaces were found to be enclosed in a layer of primary bone resistant to resorption associated with surface modeling. It is proposed, that this drift barrier is maintained by a control mechanism present inside the perilymphatic space.

Normal quantum type bone remodeling was studied in temporal bones of young domestic pigs by means of combined microradiography, osteofluorochrome labelling and osteoid staining. Evolving secondary osteons were morphologically normal although much less in the otic capsule than in the surrounding compacta of the temporal bones or in long bones. Moreover, remodeling was totally absent in bone tissue immediately adjacent to perilymphatic spaces suggesting the presence of a local mechanism controlling resorption and perhaps formation in the bony otic capsule.