Medication-related osteonecrosis and osteoradionecrosis of the jaws: Update and current management.

Medication related osteonecrosis of the jaws (MRONJ) and osteoradionecrosis of the jaws (ORNJ) are two different diseases of quite similar appearance. MRONJ is mainly due to antiresorptive or antiangiogenic drug therapy and ORNJ to radiotherapy. The present work aimed at presenting and comparing the current knowledge on MRONJ and ORNJ. They both present as an exposure of necrotic bone and differ in some clinical or radiological characteristics, clinical course and mostly in treatment. They share similar risk factors. A tooth extraction is more frequently found as a triggering factor in MRONJ. The frequency of a maxillary localisation seems higher for MRONJ. On computed tomographic images, a periosteal reaction seems characteristic of MRONJ. More frequent pathological fractures seem to occur in ORNJ. It is mandatory, for ORNJ diagnosis, to exclude a residual or recurrent tumour using histological examination. Both MRONJ and ORNJ are challenging to treat and cannot be managed similarly. For both, it would still be worth to optimise awareness within the medical community, patients' oral hygiene and dental cares to improve their prevention and make their incidences decrease. Conservative therapy is more frequently achieved for MRONJ than ORNJ and surgical resection is more often performed for ORNJ. For both diseases, the last treatment possible in refractory cases is a surgical extensive resection with free flap reconstruction. A MRONJ classification is widely used today, whereas no consensus exists to date for ORNJ classification. We propose a classification that could play this role.

Bilateral sagittal split osteotomy training on mandibular 3-dimensional printed models for maxillofacial surgical residents.

Complications with bilateral sagittal split osteotomy (BSSO) can sometimes result from surgical inexperience. Our aim was to present a 3-dimensional printed mandibular model for BSSO training in a maxillofacial surgical education programme. A polymethacrylate mandibular model obtained from mandibular cone-beam computed tomographic (CT) images was designed and printed for use in training. Twenty-four residents were each asked to do a BSSO according to the Epker/Dal-Pont technique. The session was conducted as a simulation course with a final debriefing. A questionnaire before and after the test was filled in using a 10-point Likert scale to assess the participants' knowledge. The mandibular model provided a realistic way of handling the trabecular bone after cortical osteotomy, as well as in the splitting phase. Significant increases in knowledge and surgical skills were noted for all steps of the BSSO, particularly regarding the use of the piezoelectric device for osteotomy, and for management of wisdom teeth in the splitting zone (3.00 ±2.16 to 6.95 ±2.06 and 2.73 ±1.91 to 5.75 ±2.63, respectively; p1=0.0002 and p2=0.0003). We think that this is a valuable printed mandibular model for the development of surgical skills for BSSO in maxillofacial surgical residents.

Costal graft as a support for bone regeneration after mandibular juvenile ossifying fibroma resection: An unusual case report.

Spontaneous regeneration of bone tissue after mandibular resection is rare in adults, although it does often take place in children. Periosteum conservation appears to play a major role in this healing process. We here report regarding a 5-year-old boy who exhibited a large mandibular trabecular juvenile ossifying fibroma. The lesion was treated by mandibulectomy, with careful preservation of the periosteal layer and immediate reconstruction with a costal graft by an intraoral approach. Monitoring over the course of a year revealed spontaneous mandibular regeneration, and it allowed for a series of measurements of the graft to be made. During this follow-up period, the mandibular height increased from 41.5% to 75.2% (P=0.0008) of the height of the unaffected mandibular height, while the width grew from 34.4% to 82.8% (P=0.0078) of the width of the healthy side, thus demonstrating the importance of a conservative approach regarding the periosteum in such situations. The costal graft acted as a support for bone regeneration by immobilizing the remaining bone fragments and by preventing soft-tissue prolapse.

Vertical ramus elongation and mandibular advancement by endobuccal approach: Presentation of a new osteotomy technique.

INTRODUCTION: Several surgical procedures have been proposed for the treatment of hyperdivergent dentoskeletal deformities. We propose a new osteotomy technique allowing for lengthening and advancement of the mandibular ramus by intra-oral approach. SURGICAL PROCEDURE: This technique differs from the conventional sagittal split osteotomyin that which the anterior osteotomy line is not continued until the basilar edge but stopped 5-6mm above it. Cutting of the pterygomasseteric sling is systematically done allowing for the lowering of the mandibular angle. Osteosynthesis is performed by transjugal and intra-oral approaches, using two adjustable miniplates. Our supra-angular technique allows for both elongation of the ramus and advancement of the mandible. Unlike the vertical ramus osteotomy proposed by Caldwell-Letterman, external incision and intraoperative cervical hyperextension are not required.

[Oropharyngeal toothbrush perforation in an infant]. / Plaie transfilante oropharyngée par une brosse à dent chez un nourrisson.

INTRODUCTION: Oral impalement injuries are common in children. We report a case of severe pharyngeal toothbrush perforation in a 15-month-old infant. OBSERVATION: A 15-month-old child was admitted for a penetrating oral injury caused by a toothbrush. There was no hemorrhagic or neurological complication. A CT scan showed the toothbrush in the right parapharyngeal region with its extremity in the mastoid region. Exploration and extraction of the toothbrush was performed under general anesthesia. The outcome was uneventful. DISCUSSION: Penetrating oral cavity wounds caused by a toothbrush in children may be severe and must be explored in the operating room. A preoperative CT scan must be performed to complete the assessment of lesions. The risk of infection is high and an antibiotic prophylaxis is recommended. Neurological and vascular complications may occur but they are rare.

Activation of platelets by microfibrils and collagen. A comparative study.

Previous works demonstrated that microfibrils stimulate blood platelets to aggregate. The present study compares the activation of platelets by human placental and bovine aortic microfibrils and by type III collagen. We studied the morphological changes occurring in in platelets during their activation and aggregation, as well as the kinetics of the release reaction and thromboxane B2 formation. As for collagen, the microfibrils-induced platelet aggregation followed a lag phase, during which progressive emission of pseudopodes and centralization of organelles occurred. Aggregation was associated with secretion of beta-thromboglobulin and adenylic adenylic nucleotides, and with formation of thromboxane B2; it was established that the kinetics of secretion and the aggregation curve were parallel. Microfibrils-induced aggregation was also inhibited by ethylenediamine tetraacetic acid, creatine phosphate-creatine phosphokinase, and aspirin, showing that it was calcium-dependent and required a secretion of ADP and formation of endoperoxide and thromboxane. The response to microfibrils was much more rapid than to collagen; placental microfibrils reacted faster than aortic microfibrils. The requirement of plasma in the microfibrils platelets interaction was confirmed: 10 microliters is the minimal amount of plasma necessary for an aggregation of platelets in 400 microliters of buffer. This fact supports the idea of the existence of two different pathways in the interaction between platelet and the subendothelium, depending on the vascular structure (microfibrils or collagen) involved, even though the sequence of events leading to the formation of an aggregate is similar.

Aortic endothelial cells in culture secrete glycoproteins reacting with blood platelets.

The culture medium of bovine aortic endothelial cells contains proteins which inhibit the aggregation of platelets induced by aortic microfibrils but not by type III collagen. From this medium, fibronectin, thrombospondin and a glycoprotein with MW of 128 Kd (GP 128), similar to a glycoprotein described in a microfibrillar extract from bovine aorta were separated by affinity and ion exchange chromatography. GP 128 was further purified by molecular sieve chromatography on SW 3000 column. GP 128 inhibited the aggregation of platelets by microfibrils. This suggests a role of GP 128 in the platelet/subendothelium interaction.

[Collagen nonapeptide, a trap for platelets]. / Nonapeptide du collagène, leurre pour les plaquettes.

Biochemical methods involving chemical and enzymatic cleavage of type III collagen (characteristic of arterial subendothelium) have led to the identification of a nonapeptide common to different overlapping collagen fragments capable of interacting with platelets. This nonapeptide has been synthesized; it specifically inhibits platelet aggregation and secretion of endogenous platelet serotonin by type III collagen from which it originates. Its effect on platelet adhesion is moderate. In view of its specificity in the platelet-collagen interaction, its use as a mean of preventing thrombosis can be envisaged.

The molecular interaction between platelet and vascular wall.

Two different subendothelial macromolecules have been identified as being thrombogenic: collagen and the microfibrils associated with elastin. The interaction between platelets and collagen involves the binding of platelet membrane receptors by numerous sites repeatedly staggered along a collagen fiber: this explains why the preservation of ordered structures (quaternary and tertiary structures) is so important in the reactivity of collagen towards platelets. In the case of Type III collagen, a nonapeptide has been identified as possibly being part of these repetitive sites. The microfibrils have not yet been characterized, although the biochemical data presently available show that they are acidic glycoproteins resistant to collagenase. Microfibrils extracted from human placenta or bovine aorta induce the aggregation of platelets in a reaction which involves platelet glycoprotein Ib and FVIII/vWF. A general model proposed for explaining platelet adhesion to subendothelium suggests that two different mechanisms should be envisaged depending on the thrombogenic macromolecules (collagen, microfibrils) involved.

Nonenzymatic glycosylation of collagen in diabetes: incidence on increased normal platelet aggregation.

The effect of normal and nonenzymatically glycosylated rat type I acid-soluble collagen on normal human platelets was investigated. Glycosylated collagen was obtained either after in vitro incubation with glucose or from rats made diabetic by streptozotocin. The amount of nonenzymatically bound glucose was as follows: normal 2.3, diabetic 7.6 and in vitro glycosylated collagen 9.0 nmol/mg. When investigated under conditions leading to identical diameters and molecular packings for all the samples, the aggregation potency was markedly stronger for diabetic and glycosylated collagens than for normal ones. These results show the potential role of this posttranslational modification of collagen which can be considered as a risk factor in the thrombotic pathogeny of diabetes.

Interaction of blood platelets with a microfibrillar extract from adult bovine aorta: requirement for von Willebrand factor.

Adult bovine aortic tissue was treated with 6 M guanidinium chloride in the presence of proteinase inhibitors to obtain an extract that was essentially devoid of collagenous components and appeared homogeneous by electron microscopy. When this extract was dispersed by sonication it was found to be a very potent inducer of human platelet aggregation. This interaction required the presence of von Willebrand factor and of its receptor (glycoprotein Ib) on platelet membrane. This was demonstrated by the fact that the aggregation of normal blood platelets resuspended in plasmas deficient in von Willebrand factor was significantly diminished as compared to aggregation in control plasma. Moreover, this aggregation was inhibited by a monoclonal antibody, IgG AN51, to platelet glycoprotein Ib. These studies provide direct biochemical evidence for the existence of a thrombogenic constituent of the vessel wall that is noncollagenous and von Willebrand factor-dependent.

[Thrombogenicity of the vessel: role of microfibrils and of collagen]. / Thrombogénicité du vaisseau: rôle des mcirofibrilles et du collagène.

Thrombogenicity of the vessel wall: role of the microfibrils and collagen. The study of platelet adhesion to rabbit aortic subendothelium preincubated with highly specific collagenase has revealed that platelets adhere to the microfibrils of the elastic lamina. To certify that an interaction between microfibrils and platelets can occur, microfibrils from two different origins were isolated: placental microfibrils extracted from the villi of human placenta, and aortic microfibrils extracted from adult bovine aorta. Both preparations were histologically homogeneous, and differed in their amino acid composition with an acidic character more pronounced for placental than for aortic microfibrils. Both preparations were able to induce platelet aggregation in plasma, but not after platelet isolation and resuspension in buffer. An interesting feature was the fact that when normal platelets were isolated, washed and resuspended in plasma from severe VWD patients, they were not aggregated by placental or aortic microfibrils. This defect was corrected after perfusion of cryoprecipitate to one patient. Moreover, monoclonal antibody directed against platelet glycoprotein Ib inhibited the aggregation of platelets to microfibrils, not to collagen; this suggested that an axis platelet GPI-FVIII/VWF-microfibrils could represent a pathway for platelet/subendothelium interaction. The adhesion of platelets to collagen seems to involve the staggering of a short amino acid sequence along a collagen fibre. This possibility arises from the requirement for the preservation of the quaternary structure of collagen in the induction of platelet adhesion/aggregation in vitro, and also from the identification and synthesis of a nonapeptide derived from type III collagen, which is also to specifically inhibit the aggregation of platelets by collagen, following its binding to platelet membrane.

Histochemical and ultrastructural characterization of subendothelial glycoprotein microfibrils interacting with platelets.

The interaction of human blood platelets with collagenase-treated rabbit subendothelium was studied by histochemical ultrastructural methods and by morphometric semi-quantitative analysis. Aortas were deendothelialized and incubated: 1) with a highly purified bacterial collagenase whose specificity was controlled; and 2) with the same collagenase followed by chymotrypsin. For histochemical studies, tannic acid, ruthenium red, and peroxidase-labeled Ricinus communis and concanavalin A were used. Electron microscopy showed that after digestion of fibrillar collagen by collagenase, adherent and aggregated platelets were observed on Ricinus communis-, concanavalin A-, and ruthenium red-positive glycoprotein microfibrils. After successive incubation with collagenase and chymotrypsin, the microfibrils disappeared. No platelets were observed on the remnant amorphous elastin. Morphometric analysis confirmed the interaction of platelets with collagenase-treated subendothelium. In addition, glycoproteins were extracted from collagenase-treated rabbit aortas using 5 M guanidine. Using an in vitro quantitative test, significant platelet adhesion to these glycoproteins was observed. Our results show an interaction between platelets and noncollagenic glycoprotein microfibrils.

[Relation between the wall structure and modifications of the blood content (author's transl)]. / Relations entre la structure de la paroi et les modifications du contenu sanguin.

In view of its anatomical position, physical characteristics and metabolism, the endothelial cell plays a major part in maintaining the integrity of the vascular system and in the relation between the blood content, both plasma and blood cells, and the wall structure. Where this continuous single layer undergoes anatomical or functional changes, a new equilibrium is set up, an equilibrium which is multifactorial and dynamic. It is governed by the vascular and blood components and by their interrelation; it varies as a function of time and of the biorheological conditions. The interrelationship between the blood content and the wall plays an important part in vascular pathology, especially of the degenerative and thrombotic type. A better understanding of these factors will enhance the possibility of preventing atherogenesis and lay the basis for a coherent and effective therapeutic attitude thrombosis.

[The adhesion of blood platelets to collagen: molecular features of collagen (author's transl)]. / Adhésion des plaquettes sanguines au collagène. Caractéristiques moléculaires du collagène.

This review deals with some structural features of the collagen molecules involved in the adhesion of platelets representing the initial step of hemostasis, thrombosis, and (partly) atherosclerosis. The adhesion occurs at the level of a vascular lesion or deendothelialized area, whatever the genetic type of collagen. In vitro experiments with purified collagens have shown that vascular interstitial collagens (types I and III, the latter present in subendothelium) as well as basement membrane-derived collagens (types IV and V) induce an adhesion of platelets, provided that an ordered arrangement linked to the quaternary and tertiary structures of their molecule is preserved. Whatever the quaternary structure, the important point seems to be the size of the fibers and more precisely the availability of an optimal number of adhesion sites on multimerized fibers. Various direct or indirect proofs (for example, the occurrence of the impairment of collagen multimerization on platelet adhesion/aggregation) are reviewed. Our recent studies on interstitial collagens have shown the involvement of certain specific amino-acid sequences obtained after cyanogen bromide cleavage of collagen. These are the C-terminal alpha1 (I) CB6 peptide of the alpha 1 chains of type I collagen (216 amino acids) and the central alpha1 (III) CB4 peptide from type III collagen (149 amino acids) Cleavage of this last peptide by chymotrypsin, hydroxylamine, and trypsin has suggested the possibility that a nonapeptide (sequence gly-lys-hyp-gly-glu-hyp-gly-pro-lys) is a minimum site of adhesion for platelets. This assumption has been reinforced by the fact that a synthetic nonapeptide with this sequence specifically inhibits the aggregation of platelets to collagen in vitro. The adhesion of platelets may consequently be due to the repetitive staggering of short amino acid sequences (such as this nonapeptide from type III collagen) along the rigid structure formed by a multimerized collagen fiber.