The role of bone resorption in the etiopathogenesis of acquired middle ear cholesteatoma

Abstract

Cholesteatoma is a destructive squamous epithelial lesion of the temporal bone which gradually expands and leads to serious complications by destruction of nearby bony structures. Erosion caused by bone resorption of the ossicular chain and bony labyrinth may result in hearing loss, vestibular dysfunction, facial paralysis, labyrinthine fistulae and intracranial complications. The exact underlying cellular and molecular mechanism of bone resorption in acquired cholesteatoma still remains unexplained. Pubmed database and China National Knowledge Infrastructure were screened for articles focusing on bone resorption in acquired cholesteatoma. Osteoclast activation, pressure necrosis, acid lysis, enzyme mediation, inflammatory mediators and several newly discovered biomolecules are outlined as main theories behind bone resorption in acquired cholesteatoma, aiming to facilitate the development of potential therapeutic targets for preventing intracranial and extracranial complications caused by bone resorption in acquired middle ear cholesteatoma.

Readout-Segmented Echo-Planar DWI for the Detection of Cholesteatomas: Correlation with Surgical Validation

“…C holesteatoma is defined as a mass of keratinizing squamous epithelium in the tympanic cavity, mastoid cells, and the subepithelial connective tissue that can lead to an inflammatory reaction by the progressive accumulation of keratin debris and bone resorption. [1][2][3] Cholesteatoma can only be cured by surgical removal of the entire mass. 4 Depending on the surgical technique, the prevalence of residual or recurrent cholesteatoma is as high as 25%.…”

SEM BSE 3D Image Analysis of Human Incus Bone Affected by Cholesteatoma Ascribes to Osteoclasts the Bone Erosion and VpSEM dEDX Analysis Reveals New Bone Formation

“…IL-1, IL-6, TNF-α, and prostaglandin E2 (PGE2) have been investigated as inflammatory mediators of cholesteatoma progression. They are assumed to enhance bone resorption by activating osteoclasts [30][31][32], and inflammation has been confirmed to be essential for cholesteatoma formation, growth, and expansion, 5 Scanning including the bone resorption process [22,33,34]. Inflammatory cells were observed in our samples; in Figure 10, a rare coexistence of a macrophage (blue), a lymphocyte (red), and an osteoclast is presented [35][36][37].…”

“…Moreover, our observation and processing image workflow are the first in the literature showing the presence not only of bone erosion but also of matrix vesicles releasing their content on collagen bundles and selfimmuring osteocytes, all markers of new bone formation on incus bone surface. On the basis of recent literature [22][23][24][25][26][27][28][29][30][31][32][33][34], it has been hypothesized that inflammatory environment induced by CHO may trigger the osteoclast activity, eliciting bone erosion; we can provide a morphological evidence of this hypothesis in Figure 9; in fact, a T-lymphocyte, a macrophage, and an osteoclast were photographed one near the other; the photograph gives the impression of witnessing the paracrine molecular dialogue between these cells [22][23][24][25][26][27][28][29][30][31][32][33][34]. The observed new bone formation probably takes place at a slower rate in respect to the normal bone turnover, and the process is uncoupled (as recently demonstrated for several inflammatory diseases that promote bone loss) thus resulting in an overall bone loss.…”

“…Prominent theories on bone resorption in CHO are osteoclast activation; pressure necrosis; and acid lysis, enzyme mediation, and inflammatory mediation [22]. The mechanism of bone erosion in middle ear cholesteatoma remains still unclear, although its histopathology has been intensively studied.…”

Why does the acquired cholesteatoma trigger resorption of the temporal bone?

“…We have read with great interest the article “The role of bone resorption in the etiopathogenesis of acquired middle ear cholesteatoma” by Xie et al [ 1 ]. The authors presented review article about bone resorption in acquired cholesteatoma.…”