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

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.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 ossicles are located in the air-filled middle ear and serve for transmission of sound-induced mechanical vibrations from the eardrum to the oval window of the fluid-filled cochlea 2 . Damage or deformation of the ossicular chain lead to conductive hearing loss 3 . While malleus and incus develop from the first pharyngeal arch, the stapes which is the smallest bone in the human body has two embryologically distinct parts. In fact, the cranial end of the second pharyngeal arch forms an independent anlage, which develops into a superior and an inferior part. The superior part gives origin to the base of the stapes, whereas the inferior part forms the limbs (anterior and posterior crus) and the head of the stapes 4 . As sound transmission is the major function of the auditory ossicles and biomechanical loads are minor 5 , adaptive bone remodelling might be unnecessary here. In general, the absence of bone remodelling as seen with aging would be associated with hypermineralization of the bone matrix itself, but also 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 . Hypermineralized osteocyte lacunae accumulate in aged 6 , osteoporotic 9 and osteoarthritic 10 bone. In the ossicles, increased numbers of dead osteocytes as a sign of impaired bone remodelling have been reported 11,12 , however the degree of miner...

Early Changes in Cement–Bone Fixation Using a Novel Rat Knee Replacement Model

“…The most surprising finding from this study was the continued mineralization of the interdigitated bone over time following cementing of the tibia. Hyper‐mineralization of bone is known to occur in auditory ossicles and is accompanied by osteocyte death and low‐bone remodeling . Several proteins have been identified as having roles in controlling local matrix mineralization, and osteocyte death through apoptosis or necrosis could release these proteins locally, contributing transiently to local matrix mineralization.…”

“…Hypermineralization of bone is known to occur in auditory JOURNAL OF ORTHOPAEDIC RESEARCH ® OCTOBER 2019 ossicles and is accompanied by osteocyte death and lowbone remodeling. 19,20 Several proteins have been identified as having roles in controlling local matrix mineralization, 21 and osteocyte death through apoptosis or necrosis could release these proteins locally, contributing transiently to local matrix mineralization. The hyper-mineralized interdigitated bone found in the current study exhibited extensive osteocyte death and low bone turnover, suggesting that the mechanism of action may be similar to that documented in auditory ossicles.…”

On the Origins of Fracture Toughness in Advanced Teleosts: How the Swordfish Sword's Bone Structure and Composition Allow for Slashing under Water to Kill or Stun Prey

“…[16] Aging and disease affect bone quality [4,7,20,[23][24][25] and can increase the risk of fracture. [26][27][28][29] Aging effects are strongly associated with reduced osteocyte viability and interconnection, [8,10,13] bone mineralization, [23,30] and decreased mechanical competence. [20] Increasing age, for example, decreases the interface mineralization discrepancy of cement lines and surrounding tissue, [30] a key factor for toughening.…”

Human Auditory Ossicles as an Alternative Optimal Source of Ancient DNA

“…The ossicles effectively allow humans to hear by transmitting sound-induced mechanical vibrations from the outer to the inner ear. Though the ossicles do not experience high-strain biomechanical loading, they are subject to unique vibrational patterns that impact their development and characteristics over the course of an individual’s lifespan (Rolvien et al 2018). In contrast to the majority of the human skeleton, but similar to the cochlea, the auditory ossicles present with their final size and morphology at birth following the onset of the ossification of between 16 and 18 weeks in utero and the completion of ossification around 24 weeks gestational age (Marotti et al 1998; Yokoyama et al 1999; Cunningham et al 2000; Duboeuf et al 2015; Richard et al 2017).…”

“…Like the cochlea, ossicular bone tissue is rapidly modeled around the time of birth; although it may undergo further postnatal maturation, there are no signs of bone remodeling observed above the age of one year (Richard et al 2017; Rolvien et al 2018). The inhibition of bone remodeling of the auditory ossicles is evident from features such as the presence of a dense meshwork of collagenous fibers organized in an interlacing woven pattern, a smooth fibrous appearance, and limited vascular channels and viable osteocytes (Marotti et al 1998; Chen et al 2008).…”