Le canal dentaire et le nerf alvéolodentaire

International audienc

La microarchitecture du tissu osseux

Le capital osseux se constitue au cours de la vie par les mécanismes de modelage et de remodelage. Le tissu trabéculaire est constitué par un ensemble de travées (plaques et piliers) dont la répartition est hautement anisotrope : les travées se disposent parallèlement à la résultante des lignes de contraintes (Loi de Wolff). La microarchitecture trabéculaire apparaît conditionnée par les contraintes mécaniques qui s’exercent sur les pièces squelettiques. Cependant, peu de méthodes sont actuellement validées cliniquement pour apprécier et suivre l’évolution de la microarchitecture dans les ostéopathies. Les études les plus développées portent sur l’appréciation microarchitecturale par histomorphométrie osseuse grâce à l’utilisation de nouveaux algorithmes permettant d’apprécier en 2D différentes caractéristiques trabéculaires dont la connectivité. Plusieurs travaux ont montré que l’appréciation de la microarchitecture devait utiliser plusieurs techniques indépendantes. La microtomographie X (microCT), la micro IRM, le synchrotron permettent aussi de mesurer en 3D l’architecture trabéculaire de façon non destructive sur des prélèvements osseux. Cette revue décrit l’évolution des connaissances sur la microarchitecture osseuse, son rôle dans les maladies osseuses comme l’ostéoporose et les différentes méthodes d’évaluation histologique en 2D et en 3D

Multiple myeloma and bone

Multiple myeloma (also called Kahler\u27s disease [MM]) is a hematological malignancy of B lymphocytes characterized by the expansion of a malignant plasma cell clone in the bone marrow. Five thousand cases of myeloma are diagnosed each year in France, 54% in men. In almost all cases, the malignant plasma cells secrete a monoclonal immunoglobulin or an immunoglobulin fragment (free light chain) which can be detected in the blood and/or urine. This is currently the most common way of diagnosis after having prescribed an electrophoresis or an immunofixation of serum proteins. Indeed, MM is often preceded by a monoclonal gammopathy of undetermined significance (MGUS), which requires a long term biological monitoring. MGUS are 100 times more common than MM (and are observed in 3–4% of the population after 50 years) and their evolution towards an overt myeloma is approximately 1% per year. MM is a hematological malignancy whose incidence is correlated to the aging of the population (the mean age at diagnosis is about 70 years)

New microscopies, biomaterials: Two new axes for Morphologie

International audienc

Rachitismes et ostéomalacies à l’âge adulte

La principale cause de l’ostéomalacie chez l’adulte est la déficience sévère et prolongée en vitamine D, facilement reconnue aujourd’hui par le dosage de la 25-hydroxyvitamine D [25(OH)D]. Le contexte clinique, des anomalies biologiques phosphocalciques, des anomalies sur les examens d’imagerie (radiographies standard, scintigraphie osseuse), une densité parfois très basse mesurée en densitométrie osseuse, permettent d’évoquer la possibilité d’un trouble de la minéralisation de type ostéomalacique, diagnostic éventuellement confirmé par les données histomorphométriques de la biopsie osseuse trans-iliaque après double marquage aux cyclines. Une cause à la carence en vitamine D doit être recherchée et traitée. La supplémentation simple en vitamine D permet de guérir les patients. Des formes rares d’ostéomalacie, dénommées rachitismes vitamino-D-résistants (dépendants, type 1 et 2), sont dues à une anomalie génétique enzymatique (rachitisme pseudo-carentiel de Prader ou rachitisme vitamino-D-résistant de type 1, lié à un déficit en 1-alpha hydroxylase) ou à une anomalie du récepteur à la vitamine D (VDR ; rachitisme vitamino-D-dépendant de type 2) créant une résistance des organes cibles à l’action de la vitamine D. Dans cette dernière forme, le traitement est difficile, nécessitant le recours à des doses pharmacologiques fortes de vitamine D, en complément de la forte supplémentation calcique

Technical aspects: how do we best prepare bone samples for proper histological analysis?

Histological analysis of bone is a critical step for the diagnosis of malignancies. It allows direct identification of malignant cells inside marrow spaces in case of bone metastases or hematological disorders. Bone biopsy is superior to marrow aspiration because the microarchitecture of the bone marrow is preserved, a parameter that is especially important in hematological disorders. Because marrow cells are in direct contact with bone cells (lining cells, osteoblasts, osteoclasts, and their precursors), an abnormal bone remodeling rate has been described in a variety of malignant cell proliferations when developing and expanding inside marrow spaces. Bone cells elaborate and synthesize a variety of cytokines acting on hematological precursors (e.g., M-CSF)1 and malignant cells release other cytokines active on bone remodeling2–4: it is likely that bone changes are almost always associated with bone marrow alterations and vice versa. Histomorphometric analysis is a powerful tool in the evaluation of bone remodeling in metabolic bone diseases and was also successfully applied to hematological disorders and metastases from solid tumors5,6. Bone histomorphometry is a powerful method in the early diagnosis of B-cell malignancies, and smoldering myeloma or lymphomas can be characterized in patients with a monoclonal gammopathy of undetermined significance (MGUS) several years before the tumor has shown clinical expression. Bone histomorphometry is also useful in animal models of cancer bone lesions, since it permits a precise evaluation of the bone remodeling changes induced by tumor cells7–9. However, bone histomorphometry must be done on undecalcified bone sections which allow a perfect identification of osteoid tissue (the unmineralized bone matrix recently synthesized by osteoblasts), a precise identification of osteoclasts (by using histoenzymatic detection) and histodynamic analyses (after a double tetracycline labeling in humans or using a variety of other fluorochromes in the animal). These methods cannot be used on decalcified and paraffin embedded bone, since decalcification abolishes the osteoid/bone matrix differential staining and removes the fluorochrome labels, and hot paraffin embedding destroys enzyme activities. However, decalcification and paraffin remain useful for immunohistochemistry, which is difficult and hazardous on plastic sections. The main disadvantage of polymer embedding was formerly the prolonged time for preparing bone specimens (several months when polyester resins were used). With the development of histological techniques, it is now possible to have polymer embedding methods that are as fast as conventional paraffin methods. The following techniques have been developed and improved in our laboratory during the last two decades and used on more than 3000 human bone biopsies and a large number of animal studies performed in a variety of animal species (for example, mouse, rat, chicken, dog, goat, sheep, pig)

Hypophosphatasie : diagnostic et conduite à tenir

International audienc

Disuse induced by botulinum toxin affects the bone marrow expression profile of bone genes leading to a rapid bone loss.

OBJECTIVES: Molecular events occurring in the bone marrow microenvironment of an immobilized mouse limb after Botulinum toxin (BTX) injection haven\u27t been characterized. BTX injection induces a localized disuse in which the tissue events have well been characterized. METHODS: BTX injection was performed in the right quadriceps; saline injection in the left side was used as control. Mice were sacrificed at 0, 7, 14, 21 and 28 days; tibias were used for microCT analysis; bone marrow from femurs for RT-PCR analysis. RESULTS: MicroCT revealed bone loss and microarchitectural damages on the immobilized side as from 7d; cortical area tended to be lower on the immobilized limb at 28d. Gene expression of formation factors was altered as from 7 days post-BTX: alkaline phosphatase, Tgfβ1, Lrp5, Sfrp2. Only Sfrp2 and Lrp5 were maintained altered until 28d. Expression of Dkk1 increased from 21d and represented a late inhibitor of formation. Gene expression of resorption markers increased as from 7d (Rankl, Tracp, Il1α, Il1β and Il6) and was maintained until 28d for Tracp and Il6. CONCLUSION: A localized disuse induces rapid modifications in the bone marrow gene expression leading to bone loss due to an early decrease of formation associated with an increase in resorption

Incretin-based therapy for the treatment of bone fragility in diabetes mellitus

Bone fractures are common comorbidities of type 2 diabetes mellitus (T2DM). Bone fracture incidence seems to develop due to increased risk of falls, poor bone quality and/or anti-diabetic medications. Previously, a relation between gut hormones and bone has been suspected. Most recent evidences suggest indeed that two gut hormones, namely glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), may control bone remodeling and quality. The GIP receptor is expressed in bone cells and knockout of either GIP or its receptor induces severe bone quality alterations. Similar alterations are also encountered in GLP-1 receptor knock-out animals associated with abnormal osteoclast resorption. Some GLP-1 receptor agonist (GLP-1RA) have been approved for the treatment of type 2 diabetes mellitus and although clinical trials may not have been designed to investigate bone fracture, first results suggest that GLP-1RA may not exacerbate abnormal bone quality observed in T2DM. The recent design of double and triple gut hormone agonists may also represent a suitable alternative for restoring compromised bone quality observed in T2DM. However, although most of these new molecules demonstrated weight loss action, little is known on their bone safety. The present review summarizes the most recent findings on peptide-based incretin therapy and bone physiology

3D Porous Architecture of Stacks of β-TCP Granules Compared with That of Trabecular Bone: A microCT, Vector Analysis, and Compression Study

The 3D arrangement of porous granular biomaterials usable to fill bone defects has received little study. Granular biomaterials occupy 3D space when packed together in a manner that creates a porosity suitable for the invasion of vascular and bone cells. Granules of beta-tricalcium phosphate (β-TCP) were prepared with either 12.5 or 25 g of β-TCP powder in the same volume of slurry. When the granules were placed in a test tube, this produced 3D stacks with a high (HP) or low porosity (LP), respectively. Stacks of granules mimic the filling of a bone defect by a surgeon. The aim of this study was to compare the porosity of stacks of β-TCP granules with that of cores of trabecular bone. Biomechanical compression tests were done on the granules stacks. Bone cylinders were prepared from calf tibia plateau, constituted high-density (HD) blocks. Low-density (LD) blocks were harvested from aged cadaver tibias. Microcomputed tomography was used on the β-TCP granule stacks and the trabecular bone cores to determine porosity and specific surface. A vector-projection algorithm was used to image porosity employing a frontal plane image, which was constructed line by line from all images of a microCT stack. Stacks of HP granules had porosity (75.3 ± 0.4%) and fractal lacunarity (0.043 ± 0.007) intermediate between that of HD (respectively 69.1 ± 6.4%, p < 0.05 and 0.087 ± 0.045, p < 0.05) and LD bones (respectively 88.8 ± 1.57% and 0.037 ± 0.014), but exhibited a higher surface density (5.56 ± 0.11 mm(2)/mm(3) vs. 2.06 ± 0.26 for LD, p < 0.05). LP granular arrangements created large pores coexisting with dense areas of material. Frontal plane analysis evidenced a more regular arrangement of β-TCP granules than bone trabecule. Stacks of HP granules represent a scaffold that resembles trabecular bone in its porous microarchitecture