Cholesteatoma Severely Impacts the Integrity and Bone Material Quality of the Incus.

Cholesteatoma can lead to progressive destruction of the auditory ossicles along with conductive hearing loss but precise data on the microstructural, cellular, and compositional aspects of affected ossicles are not available. Here, we obtained incus specimens from patients who had cholesteatoma with conductive hearing loss. Incudes were evaluated by micro-computed tomography, histomorphometry on undecalcified sections, quantitative backscattered electron imaging, and nanoindentation. Results were compared with two control groups taken from patients with chronic otitis media as well as from skeletally intact donors at autopsy. The porosity of incus specimens was higher in cholesteatoma than in chronic otitis media, along with a higher osteoclast surface per bone surface. Histomorphometric assessment revealed higher osteoid levels and osteocyte numbers in cholesteatoma incudes. Incudes affected by cholesteatoma also showed lower matrix mineralization compared with specimens from healthy controls and chronic otitis media. Furthermore, the modulus-to-hardness ratio was higher in cholesteatoma specimens compared with controls. Taken together, we demonstrated increased porosity along with increased osteoclast indices, impaired matrix mineralization, and altered biomechanical properties as distinct features of the incus in cholesteatoma. Based on our findings, a possible impact of impaired bone quality on conductive hearing loss should be further explored.

A Novel Diagnostic and Treatment Algorithm for Acute Mastoiditis in Children Based on 109 Cases.

BACKGROUND: Acute mastoiditis (AM) is a potentially life-threatening condition primarily affecting children. To date, there are no consistent criteria or valid guidelines for the diagnosis and treatment of pediatric AM. Therefore, this study evaluates the clinical course of AM in terms of clinical signs and treatment. In addition, a novel classification scheme for the disease and a treatment algorithm is being proposed. METHODS: Patient records over a 12-year period from a single center were reviewed to identify confirmed cases of AM in children. Data collected included clinical signs, body temperature, and infection parameters during the disease, as well as radiological imaging, antibiotics, and surgical as well as conservative treatment. In addition, a classification of the AM stages was established in accordance with the findings described and practical experience, consisting of four stages (1, mastoidal irritation; 2, mild AM; 3, advanced AM; 4, advanced AM and additional complications) with corresponding treatment recommendations. In the retrospective cohort, those AM cases that were treated alongside the classification were compared with the rest concerning clinical course and outcome. RESULTS: A total of 109 patients (mean age, 3.8 ± 3.8 years) were included. The main symptoms at hospital admission were auricular protrusion (n = 73; 67.0%), fever (n = 56; 51.4%) with a mean temperature of 38.3 ± 1.1°C, and otalgia (n = 28; 25.7%). The mean laboratory-tested levels of leukocytes and C-reactive protein at the time of hospital admission were 15.96 ± 8.7/nl and 59.6 ± 54.0 mg/L, respectively. During winter, there was a higher prevalence of AM, with peak hospital admissions in April (n = 22). The most common pathogen was Streptococcus pyogenes (32 cases). Treatment was purely conservative in four cases, whereas the remaining cases underwent surgery (41× grommet insertion, 64× plus mastoidectomy). The outcome was generally good, but in eight patients a second surgical procedure had to be performed as they showed signs of clinical deterioration. A total of 101 patients were treated according to the proposed algorithm, and all of which had a good outcome without the need for further interventions. CONCLUSION: Based on clinical experience in a large cohort of pediatric AM patients, a novel diagnostic and treatment algorithm has been developed and successfully tested in a retrospective cohort for AM in children to prevent further complications and to ease its management by pediatricians and otorhinolaryngologists in the emergency setting.

Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice.

Intact mineralization of the auditory ossicles - the smallest bones in the body - is essential for sound transmission in the middle ear, while ossicular hypomineralization is associated with conductive hearing loss. Here, we performed a high-resolution analysis of the ossicles in vitamin D receptor deficient mice (Vdr-/- ), which are characterized by hypocalcemia and skeletal mineralization defects, and investigated whether local hypomineralization can be prevented by feeding a calcium-rich rescue diet (Vdr-/- res ). In Vdr-/- mice fed a regular diet (Vdr-/- reg ), quantitative backscattered electron imaging (qBEI) revealed an increased void volume (porosity, p<0.0001) along with lower mean calcium content (CaMean, p=0.0008) and higher heterogeneity of mineralization (CaWidth, p=0.003) compared to WT mice. Furthermore, a higher osteoid volume per bone volume (OV/BV; p=0.0002) and a higher osteocyte lacunar area (Lc.Ar; p=0.01) were found in histomorphometric analysis in Vdr-/- reg mice. In Vdr-/- res mice, full rescue of OV/BV and Lc.Ar (both p>0.05 vs. WT) and partial rescue of porosity and CaWidth (p=0.02 and p=0.04 vs. WT) were observed. Compared with Hyp mice, a model of X-linked hypophosphatemic rickets, Vdr-/- reg mice showed a lower osteoid volume in the ossicles (p=0.0002), but similar values in the lumbar spine. These results are consistent with later postnatal impairment of mineral homeostasis in Vdr-/- mice than in Hyp mice, underscoring the importance of intact mineral homeostasis for ossicle mineralization during development. In conclusion, we revealed a distinct phenotype of hypomineralization in the auditory ossicles of Vdr-/- mice that can be partially prevented by a rescue diet. Since a positive effect of a calcium-rich diet on ossicular mineralization was demonstrated, our results open new treatment strategies for conductive hearing loss. Future studies should investigate the impact of improved ossicular mineralization on hearing function.

Conductive Hearing Loss in the Hyp Mouse Model of X-Linked Hypophosphatemia Is Accompanied by Hypomineralization of the Auditory Ossicles.

X-linked hypophosphatemia (XLH) is a hereditary musculoskeletal disorder caused by loss-of-function mutations in the PHEX gene. In XLH, increased circulating fibroblast growth factor 23 (FGF23) levels cause renal phosphate wasting and low concentrations of 1,25-dihydroxyvitamin D, leading to an early clinical manifestation of rickets. Importantly, hearing loss is commonly observed in XLH patients. We present here data from two XLH patients with marked conductive hearing loss. To decipher the underlying pathophysiology of hearing loss in XLH, we utilized the Hyp mouse model of XLH and measured auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) to functionally assess hearing. As evidenced by the increased ABR/DPOAE threshold shifts in the mid-frequency range, these measurements indicated a predominantly conductive hearing loss in Hyp mice compared to wild-type (WT) mice. Therefore, we carried out an in-depth histomorphometric and scanning electron microscopic analysis of the auditory ossicles. Quantitative backscattered electron imaging (qBEI) indicated a severe hypomineralization of the ossicles in Hyp mice, evidenced by lower calcium content (CaMean) and higher void volume (ie, porosity) compared to WT mice. Histologically, voids correlated with unmineralized bone (ie, osteoid), and the osteoid volume per bone volume (OV/BV) was markedly higher in Hyp mice than WT mice. The density of osteocyte lacunae was lower in Hyp mice than in WT mice, whereas osteocyte lacunae were enlarged. Taken together, our findings highlight the importance of ossicular mineralization for hearing conduction and point toward the potential benefit of improving mineralization to prevent hearing loss in XLH. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).