The effect of zoledronic acid on middle ear osteoporosis: An animal study.

Hearing function in older patients may be related to bone structure. We conducted an experiment to evaluate the effect of zoledronic acid on osteoporotic middle ear ossicles in an animal model. Our subjects were 19 female New Zealand white rabbits (38 ears) weighing 2 to 4 kg. We divided the rabbits into three groups: one group consisted of 6 rabbits with osteoporotic ears that were treated with zoledronic acid; the second group was made up of 8 rabbits with osteoporotic ears that were not treated; a control group included 5 rabbits with normal ears that were untreated. After an oophorectomy, the 6 study rabbits were administered 0.1 ml/kg of zoledronic acid intravenously. All rabbits were sacrificed 16 weeks later, and the middle ear ossicles were removed for investigation under light microscopy. Although osteoporosis enhanced the osteoclastic bone resorption of the ossicles, zoledronic acid enhanced osteoblastic activity on osteoporotic middle ear ossicles. The incidence of osteoporosis was 93.8% in the untreated osteoporosis group and 33.3% in zoledronic acid group-a statistically significant difference (OR: 0.24; 95% CI: 0.09 to 0.58; p < 0.001). Osteoporosis appears to increase the resorption of the middle ear ossicles, a process that can be avoided with zoledronic acid administration. Prevention of the effects of osteoporosis in humans may help decrease the irreversible changes in the middle ear ossicles.

Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma.

Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.

Morphometric investigation on osteocytes in human auditory ossicles.

An osteocyte lacunae differential count (1-lacunae with live osteocytes, 2-lacunae with degenerating osteocytes, 3-empty lacunae) was carried out on ear ossicles and clavicles from cadavers as well as on stapes removed by stapedotomy. The distance of the three types of lacunae from the vascular source was also determined by a computer-assisted light microscope. Results showed that the delayed fixation of bone from cadavers does not significantly interfere with osteocyte preservation, at least with the scope of this investigation. The results of osteocyte differential count show that the number of empty lacunae and lacunae with degenerating osteocytes: (a) is significantly higher in ear ossicles than in clavicles, (b) increases with age, (c) is higher in stapes than in incuses and mallei, (d) increases with the distance from the vascular sources in both ear ossicles and clavicles. Additionally it appeared that the process of osteocyte degeneration in ear ossicles is very rapid and widespread, over 40% of the cells being dead within the 2nd year of age. In the light of the recent literature and personal findings, which ascribe to osteocytes the function of mechanical detectors, and considering that bone remodeling occasionally occurs in ear ossicles, it is postulated that osteocyte death in these bones could be a programmed phenomenon (apoptosis?), due to which they lose the ability to react to strains and stresses and achieve the structural stability they need to perform their peculiar stereotyped function.

The vascular supply of the lenticular and long processes of the incus.

Previous reports of the blood supply to the lenticular and long processes of the incus have failed to consider the potential contribution of the periosteal vascular plexus. This scanning electron microscopic study of vascular foramina on the cortical bone surface demonstrates that there is no statistical difference between the numbers of vascular foramina on the lenticular and long processes, as opposed to the body and short process. These results suggest that the blood supply to this portion of the ossicular chain may not be as tenuous as has been thought.

Development of the chick's auditory ossicle, the columella.

The avian middle ear contains a single auditory ossicle that is composed of a bony columella and a cartilaginous extracolumella. The columellar footplate (clipeolus) inserts into the oval window at its proximal end. The extracolumella attaches to the tympanic membrane at its distal end. The present study was undertaken to determine the patterns of growth, chondrification, and ossification of the chick's auditory ossicle before and after hatching.

Suspension organ culture of the fetal mouse ear.

To observe the development of the fetal ear, we grew the explanted ears of mouse fetuses 13 days old in suspension organ culture on a roller device for 48 hours. We used the BGJb-medium (Fitton-Jackson Modification) supplemented by 25% fetal bovine serum, and added a solution containing penicillin-streptomycin at the rate of 1% to the total volume. It was observed histologically that some explants developed ossicles that corresponded with those of mouse fetuses 15 days old in vivo. Sensory structures in the inner ear developed in organ culture as well. This method may help to resolve the question of ontogenesis of the ossicles.

Comparative histological contributions to the development of the ear-ossicular joints and the temporomandibular joint in the mouse.

The genesis, differentiation, development and growth of the ear-ossicular joints and temporomandibular joint (TMJ) in the Slc-ICR mouse were studied by means of light and transmission electron microscopy. The differentiation of the ossicular joints and TMJ anlagen was initiated during the fetal stages. Although morphogenesis, development and growth of the TMJ were already evident in the prenatal stages, the joint-cleaving associated with the occurrence of interzones in the cartilaginous ossicular chain was observed during the neonatal stages. However, the simple diarthrodial ossicular joints were completed and became mature earlier than the double synovial TMJ having an articular disc in early postnatal life. TEM examinations revealed that the articulating epiphyseal cartilage of the ossicular joints consisted of hyaline cartilage, while the intracapsular structures in the TMJ were composed of fibrocartilage. The synovium of the diarthroidal joints was supplied by blood vessels, nerve fibers, collagen and elastic fibers. No distinct aging in the cellular and fibrous components of the synovial tissue of the completed TMJ and ossicular joints was evident in the present study.

Aspectos morfológicos de los huesecillos del oído en embriones humanos / Morphologic aspects of the ear ossicle in human embryon

Estudiamos, por medios histológicos y topográficos, aspectos evolutivos de los esbozos de los huesecillos del oído en embriones y fetos humanos. MATERIAL: Dos grupos: Grupo I. Embriones cuya edad calculada oscila entre 8 y 12 semanas (esbozos cartilaginosos). Grupo II. Edad calculada, entre 16 y 24 semanas (esbozos de osificación). El primer grupo consta de 14 casos, el segundo grupo de 7 casos (Total, 21 casos). METODOS: Cortes seriados de la cabeza y de la región auditiva. Fotos, dibujos de láminas coloreadas con hematoxilina-eosina y tricrómicos. RESULTADOS: Grupo I. Esbozos cartilaginosos rodeados por pericondrio, con los cuales forman, aparentemente, unidades de sostén. Grupo II. Esbozos formados por cartílagos en reposo o en osificación, tejido osteoide y óseo, tejido mesenquimal denso, médula ósea hematopoyética. Funciones de sostén y de hematopoyesis. Los espacios medulares disminuyen con la mayor edad de los fetos. Generalmente, estos esbozos muestran tejido óseo compacto en la periferia, con tejido osteoide y tejido esponjoso en las partes internas. Hacia las superficies auriculares, hay cartílago. La osificación en los "huesecillos", corresponde al tipo endocondral, pero sin zonas de cartílago seriado. En reconstrucciones fotográficas de los huesecillos, parece haber una zona de osificación en cada extremo, y una central pericondrial. En los esbozos cartilaginosos (primer grupo), planteamos la posibilidad de que los esbozos de yunque y martillo se desprendan como grupos separados de la llamada articulación maleo-incudal, que así representa la articulación mandibular primitiva

The development of the ossicular ligaments in the human middle ear.

We examined serially sectioned human temporal bones of fetuses and newborns from Wittmaack's temporal bone collection at the University of Hamburg. At the end of the 3rd month of fetal development, a concentration of mesenchyme arises in the area which later contains the ossicular ligaments. The anlage of these ligaments can be clearly identified in the 4th month of development. The longitudinal axis of the cells in this anlage first runs parallel with the surface of the ossicles. In the further stages of development with increasing fibrillogenesis the cells straighten out according to the physiological stresses. Differentiation of the ligaments is terminated at the end of the 9th month.

The fate of an ossicular allograft in tympanoplasty.

Correction of ossicular defects in tympanoplasty most commonly involves the use of commercially available prostheses or preserved allograft ossicles. Incus autografts and tragal cartilage autografts are also used by many surgeons. Presculptured preserved allograft ossicles have not been used widely, but are used almost exclusively by our clinic. The fate of ossicular grafts has been reported by a number of in investigators with evidence obtained at revision surgery. In this paper we will be able to trace the fate of a presculptured preserved autograft ossicle clinically and pathologically. The unique aspect of this study is the demonstration of the ossicular status in post mortem temporal bone dissection followed by histopathological serial section studies.

Comparison of ossicular replacement materials in a mouse ear model.

Four biomaterials, UF45S5 Bioglass, Silastic, Plasti-Pore, and Proplast, were used to replace the incus in a mouse ear model. Bioglass, a bioactive glass ceramic, compared favorably with the other test materials in maintaining surgical positioning between malleus and stapes and remaining stable to a blast of nitrogen gas and to pick manipulation. In a short-term animal study, Bioglass showed histocompatibility comparable to that of these other implant materials now used in ossicular replacement surgery in humans.

[The histological changes in cartilage (incus) in the middle ear after conservation--an animal study (author's transl)]. / Uber das histologische Verhalten von Knorpel (Ambossgelenkpfanne) im Mittelohrraum nach unterschiedlicher Konservierung. Eine tierexperimentelle Studie.

This study demonstrates the histological changes of incus cartilage after transplantation into the middle ear space of rabbits. Conservation was performed by deep-freezing, lyophilisation in connection with gamma-irradiation, or with Cialit in differing dilutions. Controlled deep-freezing at about -196 degrees C and uncontrolled deep-freezing at about -20 degrees C guarantee after transplantion the survival of some vital chondrocytes. The other methods of conservation cause death of all chondroxytes. Cartilage prepared by these methods demonstrates potential for new bone formation. Only the xenogenetic cartilage loses its osteogenic potential after treatment by lyophilisation in connection with gamma-irradiation. The histological value of the transplant differs according to the method of conservation. No special tendency for resorption or inflamatory reactions could be seen.