Bone regeneration in osteoporotic conditions: healing of subcritical-size calvarial defects in the ovariectomized rat.

PURPOSE: Osteoporosis is a pathologic condition characterized by low bone mass and changes in the microarchitecture of the bone tissue. Although compromised bone strength and increased susceptibility to fracture have been established, little is known regarding the process of bone regeneration in osteoporotic conditions. Accordingly, this study sought to evaluate the intramembranous bone regeneration process in an ovariectomized rat model following the establishment of calvarial subcritical-size defects (sCSDs). MATERIALS AND METHODS: Calvarial sCSDs were established in rats that had been ovariectomized (Ovx) or sham-operated 2 months previously and left to heal, unfilled, for 6 months. Bone regeneration was assessed by radiographic, densitometric, histologic, and histometric analyses. RESULTS: Radiologic and histologic analyses showed reduced new bone formation in calvarial sCSDs in Ovx animals in comparison to sham animals. Densitometric analysis of radiologic images and histometric analysis showed significant quantitative differences between groups that converged to substantiate reduced bone regeneration in Ovx animals. CONCLUSIONS: The intramembranous ossification process is impaired in the Ovx rat model. This may suggest an impairment of the bone regeneration process in clinical conditions of postmenopausal osteoporosis and highlight the requirement for selective bone regenerative strategies in affected patients.

Potential relevance of cyclooxygenase-2 expression in keratocystic odontogenic tumours - an immunohistochemical study.

There is increasing evidence that overexpression of cyclooxygenase-2 (COX-2) plays an important role in tumour growth and spread of tumours by interfering with cell proliferation, cellular adhesion, immune surveillance, apoptosis, and angiogenesis. COX-2 levels are increased in various tumours. In this study, the expression of COX-2 in 116 specimens of keratocystic odontogenic tumours (KCOT) has been analyzed. KCOT is a benign neoplasm of odontogenic origin with an occasionally aggressive behavior leading to high recurrence rates. Formalin-fixed, paraffin-embedded blocks were sectioned and used for hematoxylin-eosin (H&E) staining and incubated with an anti-COX-2 monoclonal antibody for immunohistochemical examination. Detection of the COX-2 antibody was performed with the EnVision kit. Cellular staining pattern for COX-2 was cytoplasmatic, and the staining intensities were semi-quantitatively evaluated as follows: negative (-), mild (±) or strong (+). Mild to strong expression of COX-2 was observed in 83 (71.6%) cases; 34 (29.3%) of which were mild positive and 49 (42.2%) were strong positive. COX-2 stain was detected mainly in the epithelial lining. The expression of COX-2 in KCOT and the current knowledge of the role played by COX-2 in tumorigenesis further strengthen the current concept that the KCOT should be regarded as a neoplasm. Furthermore, the multitude of markers known to be overexpressed in KCOTs is suggestive of what could be called a 'network addiction' pattern, rather than a pathological mechanism dependant on a specific activated/suppressed gene, thus explaining its aggressive behavior.

A comparative immunohistochemical analysis of COX-2, p53, and Ki-67 expression in keratocystic odontogenic tumors.

OBJECTIVE: The aim of the present study was to investigate the association between the expression of cyclooxygenase-2 (COX-2) in keratocystic odontogenic tumors (KCOT) and more commonly used markers, such as p53 and Ki-67. STUDY DESIGN: Expression of cyclooxygenase-2 (COX-2) in 20 biopsy specimens of keratocystic odontogenic tumors (KCOT) has been analyzed and compared with the expression of previously reported markers Ki-67 and p53. Formalin-fixed, paraffin-embedded blocks were sectioned and used for hematoxylin-eosin (H&E) staining and incubated with anti-cox-2, anti-ki-67, and anti-p53 monoclonal antibodies for immunohistochemical examination. Detection of the COX-2 antibody was performed with the EnVision kit. Cellular staining pattern was cytoplasmatic for COX-2 and nuclear for both Ki-67 and p-53. Molecular expressions were semiquantitatively evaluated as negative (-), mild (±) or strong (+). RESULTS: Mild to strong expression of COX-2 was observed in 20 (100%) of the cases. Fifteen (75%) of the KCOTs stained positive for p53 and 18 (90%) stained positive for Ki-67. There was no statistically relevant difference between the expressions of COX - 2, Ki-67, and p53. CONCLUSIONS: Although COX-2 has rarely been used to assess the biological activity of the KCOT, the results portrayed in the current study and the current knowledge of the overall role known to be played by COX-2 in tumorigenesis suggest that COX-2 may be an important marker involved in the biological behavior of the KCOT. Larger studies are required to improve our knowledge of the possible role of COX-2 in the pathogenic mechanism involved in KCOT.

Characterization and management of the keratocystic odontogenic tumor in relation to its histopathological and biological features.

Keratocystic odontogenic tumor (KCOT), formerly referred to as odontogenic keratocyst, is a benign neoplasm of odontogenic origin which may present an aggressive and infiltrative behavior leading to high recurrence rates. A review of the various treatment modalities, ranging from simple enucleation to radical surgery is portrayed in relation to clinical, radiological, histopathological and molecular features. Although prognostic factors based on clinico-pathologic and immunohistochemical findings for determining the potential for recurrence of KCOT still remains unclear, its use for determining the potential for recurrence of KCOT after surgical treatment may become important to successfully manage this neoplasm's aggressive behavior. The key element for future management of KCOTs will probably be based on thorough knowledge of the biological basis of this tumor, thereby enabling a more tailored treatment approach.

An overview on the expression of cyclooxygenase-2 in tumors of the head and neck.

Cyclooxygenase-2 (COX-2) levels are increased in various tumors, particularly those involving the esophagus, stomach, breast, pancreas, lung, colon, skin, urinary bladder, prostate and head and neck. Nevertheless, the tumorigenic mechanisms of COX-2 overexpression still remain poorly understood and may include mechanisms that may act at different stages of the disease. Thus, the literature shows increasing evidence that overexpression of the COX-2 plays an important role in tumor growth and spread of tumors by interfering with different biological processes such as cell proliferation, cellular adhesion, immune surveillance, apoptosis, and angiogenesis. Furthermore, the expression of COX-2 might shed some light over the physiopathology and clinical behavior of tumors of the head and neck, including benign odontogenic neoplasms of the jaws with an aggressive behavior, such as keratocystic odontogenic tumors (KCOT). Ultimately, the research of molecular markers associated with the biological behavior of tumors will help to understand the underlying molecular mechanisms and to predict the clinical outcome, leading to the development of new therapeutic applications, such as molecular-targeted treatment and patient tailored therapy.

[Osteonecrosis of the mandible induced by intravenous bisphosphonates in oncological patients]. / Osteonecrose da mandíbula associada a bifosfonatos intravenosos em doentes oncológicos.

Bisphosphonates are synthetic analogs of inorganic pyrophosphate, which are not only potent inhibitors of osteoclast-mediated bone resorption, but also present an important inhibitory activity of angiogenesis. Bisphosphonates become, since 1996, the standard of care in the management of patients with osteoporoses as well as bone metabolism alterations associated with neoplasias. In 2003 the first case-reports of bisphosphonate induced osteonecrosis of the jaws were published. The authors report 2 new cases of patients with osteonecrosis induced by bisphosphonates. Case 1: Seventy one years-old male patient, undergoing standard antineoplastic therapy and bisphosphonates due to multiple myeloma 4 years ago was referred to an oral surgeon because of bone exposure, after dental extraction. Case 2: Seventy years-old female patient undergoing treatment with bisphosphonates for adenocarcinoma of the breast was referred to an appointment of oral surgery due to bony exposure. The increasing incidence of this new entity, its physiopathological mechanisms and the nonexistence of consensual and evidence-based treatments, calls for a special attention on prevention, with special emphasis on a careful clinical examination of the oral cavity previously to the establishment of a therapeutic approach with intravenous bisphosphonates in oncological patients.