Parish P. Sedghizadeh

The Role of Microbial Biofilms in Osteonecrosis of the Jaw Associated with Bisphosphonate Therapy

Microbial biofilms have been observed and described in bone specimens of patients with bisphosphonate (BP)-associated osteonecrosis of the jaw (BONJ) and investigators are more recently suggesting that this condition essentially represents an osteomyelitis of the jaw clinically, with greater susceptibility in some patients on BP therapy. This article explains the role of microbial biofilms in BONJ and also discusses associated factors in the disease pathogenesis, which include BP effects on bone remodeling, anti-angiogenesis, matrix necrosis, microcracks, soft tissue toxicity, and inflammation and wound healing. Recent findings suggest a key role for microbial biofilms in the pathogenesis of BONJ; this has important therapeutic implications because biofilm organisms represent a clinical target for prevention and treatment efforts aimed at reducing the significant morbidity and costs associated with this condition.

Osseointegration of Dental Implants and Osteonecrosis of the Jaw in Patients Treated With Bisphosphonate Therapy: A Systematic Review

Bisphosphonate (BP) drugs are a commonly prescribed group of medications used in the treatment of metabolic and oncologic bone disorders. The aim of this study was to conduct a systematic review in order to evaluate whether patients on BP therapy are appropriate candidates for dental implants as compared to patients not taking BP drugs with respect to successful implant osseointegration and the risk of developing bisphosphonate-related osteonecrosis of the jaw. Based on the current literature, a history of oral or intravenous BP use is not an absolute contraindication for dental implant placement, and dental implants can osseointegrate successfully in this patient population. Importantly, the studies currently available on this topic are of moderate to weak strength of evidence with inherent bias and limitations, and hence results must be interpreted in this context. Well-controlled studies with higher strength of evidence and larger population sizes are required to address this topic more accurately in the future.

Expression of the serine protease DESC1 correlates directly with normal keratinocyte differentiation and inversely with head and neck squamous cell carcinoma progression

As part of ongoing studies aimed at identifying the molecular events involved in head and neck squamous cell carcinoma progression, we recently isolated a novel serine protease, DESC1. This study was conducted to further characterize DESC1.

Development of an animal model for Aggregatibacter actinomycetemcomitans biofilm-mediated oral osteolytic infection: a preliminary study.

BACKGROUNDnBiofilm-induced inflammatory osteolytic oral infections, such as periodontitis and peri-implantitis, have complex etiology and pathogenesis. A significant obstacle to research has been the lack of appropriate animal models where the inflammatory response to biofilms can be investigated. The aim of this study is to develop a novel animal model to study the host response to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans)-biofilm colonizing titanium implants.nnnMETHODSnTitanium implants were inoculated in vitro with A. actinomycetemcomitans, establishing a biofilm for 1 to 3 days. Biofilm-inoculated and control implants were transmucosally placed into rat hard palate or alveolar ridge. Analysis included documentation of clinical inflammation, polymerase chain reaction, and culture detection of A. actinomycetemcomitans and microcomputed tomography quantitation of peri-implant bone volume.nnnRESULTSnViable A. actinomycetemcomitans biofilm was successfully established on titanium implants in vitro, detected by confocal laser scanning microscopy. An inflammatory response characterized by clinical inflammation, bleeding, ulceration, hyperplasia, and necrosis was observed around biofilm-inoculated implants. A. actinomycetemcomitans was detected by polymerase chain reaction and culture analysis on 100% of biofilm-inoculated implants for up to 3 weeks and 25% for up to 6 weeks. Microcomputed tomography analysis demonstrated significantly lower bone volume (P <0.05) around biofilm-inoculated implants (29.6% ± 7.6%) compared to non-inoculated implants (50.5% ± 9.6%) after 6 weeks.nnnCONCLUSIONSnThese results describe a novel animal model where A. actinomycetemcomitans biofilm was established in vitro on titanium implants before placement in rat oral cavity, leading to an inflammatory response, osteolysis, and tissue destruction. This model may have potential use for investigation of host responses to biofilm pathogens and antibiofilm therapy.

Oral mucosal melanoma with unusual clinicopathologic features.

Oral mucosal melanoma (OMM) is an extremely rare malignancy, accounting for < 0.5% of all melanomas and all oral malignancies. The rarity of OMM, the heterogeneity in clinical and histopathologic appearances, and the paucity of molecular and genetic studies to date have limited our knowledge of the etiopathogenesis of these cancers. A 39‐year‐old Hispanic male presented for evaluation of a large, pigmented, plaque‐like and nodular growth of the maxillary gingival and palatal mucosa. On presentation, a presumptive clinical diagnosis of mucosal melanoma was made, which was confirmed by incisional biopsy with subsequent histopathologic evaluation. Macroscopically, the morphology and highly pigmented nature of the tumor was suggestive of a rarer subtype of melanoma known as animal‐type melanoma, also referred to as pigmented epithelioid melanocytoma. However, microscopically, the tumor showed histopathologic features consistent with a high‐grade acral (mucosal) lentiginous melanoma with overt cytomorphologic features of malignancy in addition to showing prominent pigment synthesis resembling animal‐type melanoma. A detailed search of the literature did not identify a previous report of OMM with prominent pigment synthesis resembling animal‐type melanoma. Identification of melanoma subtypes has specific implications for therapeutic approach, and thus their recognition is important to successful patient management.

Oral graft-versus-host disease and programmed cell death: Pathogenetic and clinical correlates

Graft-versus-host disease (GVHD) is an untoward complication of bone marrow transplantation. It is characterized by an immune-mediated attack by donor immune cells against various host cells and tissues, a process which may be associated with significant morbidity in affected patients. Oral lesions are a common sequelae and can serve as a highly predictive index to the presence of systemic GVHD. The oral lesions of GVHD are clinically and histologically lichenoid in nature and can be a challenge in terms of management. Ulcerated and painful mucosal lesions may represent a significant impediment to normal eating habits and nutritional intake, necessitating appropriate diagnosis and treatment. Importantly, recent evidence has indicated that programmed cell death, or apoptosis, is the major constituent in the pathogenesis of GVHD. Apoptosis not only plays a major role in normal growth and ontogeny, but has been shown to contribute to a wide spectrum of both inflammatory and neoplastic disorders. Since knowledge of apoptotic molecular pathways is requisite for understanding GVHD, the purpose of this paper is to provide a fundamental overview of the predominant apoptotic mechanisms implicated in the pathogenesis of GVHD and to relate these findings to the oral complications of the disease. Finally, we will discuss management strategies for diagnosing and treating the oral lesions of GVHD. By explicating the molecular events in the apoptotic pathway, unique therapeutic and pharmacologic strategies for regulating apoptosis may be developed in the future, reducing the morbidity associated with conditions like GVHD.

Original ContributionsSystematic ReviewAssessing the utility of serum C-telopeptide cross-link of type 1 collagen as a predictor of bisphosphonate-related osteonecrosis of the jaw: A systematic review and meta-analysis

BACKGROUNDnThe authors of this systematic review and meta-analysis assessed the utility of serum C-telopeptide cross-link of type 1 collagen (sCTX), a biomarker of bone resorption, as a predictor of the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ).nnnTYPES OF STUDIES REVIEWEDnThe authors searched for studies involving adult participants, written in English, and published through January 20, 2016, using the following electronic databases: the Cochrane Library, MEDLINE via PubMed, and Web of Science. They also searched Google Scholar and the reference lists of all eligible trials and reviews. They identified 16 articles that met their inclusion criteria (9 controlled studies and 7 case series). They applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. They independently extracted data in duplicate, including the characteristics of study participants, risk factors, control groups, and outcomes. They assessed risk of bias, and they resolved any disagreements between review authors through discussion.nnnRESULTSnA meta-analysis with 9 controlled studies revealed no significant difference in mean sCTX values between patients with BRONJ and control participants (difference in means,xa0-31.417; 95% confidence interval [CI], -91.560 to 28.726; P = .306). A second meta-analysis with 4 studies showed no significant difference in risk of having an sCTX value below 150 picograms per milliliter for patients with BRONJ compared with control participants (risk ratio, 1.892; 95% CI, 0.636-5.626; Pxa0= .251).nnnCONCLUSIONS AND PRACTICAL IMPLICATIONSnA systematic review of the literature with meta-analysis does not support the use of sCTX levels as a predictor of the development of BRONJ. Further prospective large sample studies are needed to understand the role of sCTX as a predictor for BRONJ.