Early bone tissue aging in human auditory ossicles is accompanied by excessive hypermineralization, osteocyte death and micropetrosis

Tim Rolvien,Michael Amling,Petar Milovanovic,Sebastian Butscheidt,Katharina Jähn,Anke Jeschke,Felix N Schmidt,Björn Busse,Klaus Püschel,Christoph Riedel

doi:10.1038/s41598-018-19803-2

Abstract

Within the mineralized bone, osteocytes form a multifunctional mechanosensitive network orchestrating bone remodelling. A preserved osteocyte population is a crucial determinant of bone quality. In human auditory ossicles, the early decrease in osteocyte numbers but maintained integrity remains an unexplained phenomenon that might serve for sound transmission from air to the labyrinth. Here we analysed the frequency, size and composition of osteocyte lacunae in the auditory ossicles of 22 individuals from early postnatal period to old age. Mineralization of the bone matrix was determined using backscattered electron imaging. No signs of bone remodelling were observed above the age of 1 year. We detected characteristics of early bone tissue aging, such as decrease in osteocytes, lower total lacunar density and lacunar area, as well as high matrix mineralization accompanied by distinct accumulation of micropetrotic lacunae and decreased indentation depths. The majority of these changes took place in the first months and years of life, while afterwards only minor reorganization was present. With osteocyte apoptosis potentially being a consequence of low mechanical stimuli, the early loss of osteocytes without initiation of bone remodelling indicates an adaptive response conserving the architecture of the auditory ossicles and ensuring stable sound transmission throughout life.

Highlights

The human auditory ossicles malleus, incus and stapes present with their final morphology at birth, while in later life decades only minor morphological changes occur[1]
Our results in the auditory ossicles show a dramatic decrease in viable osteocytes already in early childhood, which indicates that the lifespan of osteocytes might be highly site-specific
Our results indicate that high-frequency vibration in auditory ossicles goes along with osteocyte apoptosis

Summary

Introduction

The human auditory ossicles malleus, incus and stapes present with their final morphology at birth, while in later life decades only minor morphological changes occur[1]. The absence of bone remodelling as seen with aging would be associated with hypermineralization of the bone matrix itself, and with the accumulation of hypermineralized (micropetrotic) osteocyte lacunae[6,7]. The latter describes the in vivo formation of intra-lacunar calcification[8], which is believed to follow apoptosis of some osteocytes[7]. We carried out this study to investigate the changes in osteocyte characteristics and matrix mineralization in the human auditory ossicles, acknowledging that they are subject to unique vibrational patterns and do not experience high-strain biomechanical loading. Our findings may contribute to better understanding of the osteocyte’s involvement in both bone loss pathogenesis and high bone mass syndromes

Methods

Results

Conclusion