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

Abstract

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.