An aromatase polymorphism (g.132810C>T) predicts risk of bisphosphonate-related osteonecrosis of the jaw.

BACKGROUND: Bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) is an unpredictable, debilitating adverse effect. Recently, genetic polymorphisms have arisen as promising tools to identify patients with a higher risk of drug-related adverse events. AIM: We aimed to examine the association between the aromatase polymorphism g.132810C>T, and the estrogen receptor polymorphisms g.156705T>C and g.156751A>G, and the risk of BP-related ONJ. METHODS: Eighty-three subjects were included in the study. A clinical and radiological examination was conducted on oncologic subjects treated with zoledronic acid. Subjects with histologically confirmed ONJ were included in the test group (n = 30) whereas subjects with good oral health were included in control group (n = 53). Aromatase and estrogen receptor polymorphisms from blood samples were analyzed. RESULTS: The aromatase g.132810C>T polymorphism displayed an over-representation of the TT genotype in the test group (36.67 vs 16.98%; p < 0.05). There was no significant difference in either estrogen receptor polymorphism genotype frequency between the test and control groups. CONCLUSION: Our data suggest a role for the g.132810C>T polymorphism in predicting ONJ risk. These results can pave the way to the personalization of BP therapy, based on individual genotype.

Cyclooxygenase-2 expression in central giant cell lesion of the jaws: an immunohistochemical study.

Central Giant Cell Lesion (CGCL) is an uncommon benign jaw lesion, with uncertain etiology, and a variable clinical behavior. Studies of molecular markers of CGCL, may help understanding better the nature and behavior of this lesion, and eventually may represent a definitive target to pharmacological approach in the treatment of CGCL. Chronic inflammation has been found to mediate a wide variety of diseases including neoplasms. Among the gene products involved in the induction of the inflammatory process, Cyclooxygenase 2 (COX-2) has been shown to have a close relationship with tumorigenesis, however COX-2 expression has never been evaluated in CGCL. The aim of the study was to investigate the expression of COX-2 in CGCL. Immunohistochemical assessment for COX-2 expression was performed in 18 patients previously diagnosed with CGCL. Multinucleated giant cells (MGC) and mononucleated stromal cells (MSC) were used in the slide analysis. Among the patients studied, 10 were male and 8 were female, with a median age of 15.4 years. Lesions in the mandible were observed in 11 cases and 7 were found in the maxilla. There were 9 aggressive and 9 non-aggressive CGCLs. COX-2 immunopositivity was present in only 3 cases stained in both MGC and MSC. All 3 cases presented with ulcerations in the mucosa lesion, suggesting that the COX-2 expression is due to the presence of inflammation. This study does not support the involvement of COX-2 in the etiophatogenesis of CGCL.

Overexpression of matrix metalloproteinase (MMP)-1 and -9 in central giant cell lesions of the jaws: implications for clinical behavior.

OBJECTIVE: The aim of this study was to investigate the relationship between the immunohistochemical expression of MMP-1 and MMP-9 with the clinical behavior of central giant cell lesions (CGCLs) of the jaws. STUDY DESIGN: Paraffin-embedded tissue from 30 aggressive and 12 nonaggressive CGCLs was assessed for the expression of MMP-1 and MMP-9 using immunohistochemistry. RESULTS: Although cellular immunolocalization patterns of MMP-1 and MMP-9 were similar, mean values of expression estimation/SID scores of each protease were significantly higher in aggressive CGCLs in comparison with nonaggressive lesions. Moreover, linear regression analysis showed that there was a reasonably good correlation not only between the expression estimation but also among SID scores of the 2 proteolytic enzymes. CONCLUSION: The findings of this study suggest a role for MMP-1 and MMP-9 in the resorptive activity of different cellular groups in CGCLs and indicate that differences in immunoreactivity of these 2 proteolytic enzymes may underlie the distinct clinical behavior.

Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis.

We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 x 10(-6), P = 4.231 x 10(-6), P = 6.22 x 10(-6), and P = 2.15 x 10(-6), respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5).

Oral fluid-based biomarkers of alveolar bone loss in periodontitis.

Periodontal disease is a bacteria-induced chronic inflammatory disease affecting the soft and hard supporting structures encompassing the teeth. When left untreated, the ultimate outcome is alveolar bone loss and exfoliation of the involved teeth. Traditional periodontal diagnostic methods include assessment of clinical parameters and radiographs. Though efficient, these conventional techniques are inherently limited in that only a historical perspective, not current appraisal, of disease status can be determined. Advances in the use of oral fluids as possible biological samples for objective measures of current disease state, treatment monitoring, and prognostic indicators have boosted saliva and other oral-based fluids to the forefront of technology. Oral fluids contain locally and systemically derived mediators of periodontal disease, including microbial, host-response, and bone-specific resorptive markers. Although most biomarkers in oral fluids represent inflammatory mediators, several specific collagen degradation and bone turnover-related molecules have emerged as possible measures of periodontal disease activity. Pyridinoline cross-linked carboxyterminal telopeptide (ICTP), for example, has been highly correlated with clinical features of the disease and decreases in response to intervention therapies, and has been shown to possess predictive properties for possible future disease activity. One foreseeable benefit of an oral fluid-based periodontal diagnostic would be identification of highly susceptible individuals prior to overt disease. Timely detection and diagnosis of disease may significantly affect the clinical management of periodontal patients by offering earlier, less invasive, and more cost-effective treatment therapies.

[The pathogenesis of surgical trauma and the characteristics of its course in planned surgical interventions in the maxillofacial area]. / Patogenez operatsionnoi travmy i osobennosti ee techeniia pri planovykh khirurgicheskikh vmeshatel'stvakh v cheliustno-litsevoi oblasti.

Examinations carried out on 76 patients have shown that systematic surgical interventions into the maxillofacial area produce deep changes in the tissue and serum systems of proteolysis and their inhibitors. Activation of proteolytic enzymes already on the stage of surgical trauma leads to the formation in the operative wound of the focus of endotoxicosis which depresses antitryptic activity of injured tissues and thus promotes the development of purulent complications. The study of the above indexes at the early stages of acute period may serve as a diagnostic test while estimating a severity of operative wound and allows to make prognosis of the development of purulent complications.

[Central reparative giant cell granuloma of the jaw. Morphological study]. / Granulome réparateur central à cellules géantes des maxillaires. Etude morphologique.

8 cases of central giant cell reparative granuloma of the jaws were morphologically studied. If the histological feature of this disease is theoretically characteristic (giant cells, fusiform cells, numerous vessels and more or less active osteogenesis) in fact other giant cells lesions, especially true giant cell tumors, often set a problem to the pathologist. In addition, the etiopathogenesis of that granuloma is discussed by means of the results of immunohistochemical, histoenzymological and ultrastructural findings.

Suxamethonium-induced jaw stiffness and myalgia associated with atypical cholinesterase: case report.

An 11-year-old boy was given halothane, nitrous oxide and oxygen, pancuronium 0.4 mg and suxamethonium 100 mg for induction of anaesthesia. In response to this a marked jaw stiffness occurred which lasted for two minutes and the anaesthesia were terminated. Four hours of apnoea ensued and he suffered generalized severe myalgia lasting for one week. He was found to have atypical plasma cholinesterase with a dibucaine number of 12, indicating homozygocity. This was verified by study of the family. The case shows that prolonged jaw rigidity and myalgia may occur after suxamethonium in patients with atypical cholinesterase despite pretreatment with pancuronium.

1-naphthyl acetate esterases in fluids and tissues of jaw cysts.

The activity and electrophoretic mobility of 1-naphthyl acetate esterases in cystic fluids and cystic tissues of ameloblastomas, follicular and apical cysts were examined. The cystic fluids showed lower activities than sera but had very similar patterns on the electrophoretogram. The activity levels of the three kinds of cystic fluids were not statistically significantly different. The fluid esterases may have originated from serum but they were not produced by the cystic lining tissue. Ameloblastoma tissues showed the highest activity per wet weight and per mg protein of the three kinds of cyst lesions (P less than 0.05). On the electrophoretogram, the esterase-I activity constituted 41% of the total activity in ameloblastomas, whereas in follicular cysts and apical cysts the esterase-I activity constituted 32% and 24% of the total activity, respectively.

A study of biological chemistry on the nature of jaw cysts. On the maintainance of homoeostasis in jaw cyst fluid.

Jaw cyst lining cells have an active transporting mechanism for Na+ ion and K+ion, a secreting mechanism and a selecting mechanism, and they allow permeation of electrolytes, lipids and protein into cysts. The components within the cysts have a controlling metabolism, and keep the system stable. Tumour wall cells of cystic ameloblastoma have only a passive transporting mechanism for various substances. Their nature differs from that of jaw cyst lining cells.