Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is clinically defined as a non-healing jawbone ulcerative-necrotic lesion appearing after dental therapy or minor trauma in patients treated previously with anti-resorptive, anti-angiogenic or immunomodulators. Older patients with osteoporosis and cancer receive these pharmacological agents regularly. As these patients are long-term survivors, efficient treatment is of paramount importance for their quality of life. METHODS: Literature searches via PubMed were conducted to identify relevant MRONJ studies. Basic information on MRONJ classification, clinical features, and pathosphysiology is presented herein as well as various clinical studies dealing with MRONJ in patients with osteoporosis and cancer. Lastly, we discuss current managment of patients and new trends in treatment of MRONJ. RESULTS: Although close follow-up and local hygiene have been advocated by some authors, severe forms of MRONJ are not responsive to conservative therapy. At present, there is no "gold standard" therapy for this condition. However, as the physiopathological basis of MRONJ is represented by the anti-angiogenic action of various pharmacological agents, new methods to increase and promote local angiogenesis and vascularization have recently been successfully tested in vitro, limited preclinical studies, and in a pilot clinical study. CONCLUSIONS: It appears that the best method implies application on the lesion of endothelial progenitor cells as well as pro-angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and other related molecules. More recently, scaffolds in which these factors have been incorporated have shown positive results in limited trials. However, these studies must be replicated to include a large number of cases before any official therapeutic protocol is adopted.

Influence of Section Thickness on the Accuracy and Specificity of Histometric Parameters Using Confocal Laser Scanning Microscopy in a Canine Model of Experimental Peri-Implantitis-A Proof of Concept.

OBJECTIVES: Tissue breakdown was assessed by confocal laser scanning microscopy (CLSM) using autofluorescence around implants with ligatures, on a dog hemimandible. Influence of section thickness on the accuracy of histometrical observations was also evaluated, in comparison with thin sections in light microscopy. MATERIAL AND METHODS: Three months after tooth extraction, implants were placed. Two months after abutment placement, ligatures were placed with no plaque control. 11 months post-implantation, the animal was sacrificed. Undecalcified thin (30 µm) sections were cut, stained and evaluated by light microscopy to be used as a reference. Additional sections were performed, so that another pair of unstained thick sections resulted (250-300 µm). Tissue loss was assessed using histomorphometric parameters under CLSM and was compared to the light microscopy reference ones. RESULTS: Morphometry confirmed tissue loss more pronounced on the "thick" and quick sections, when compared to the time-consuming and technique-sensitive "thin" ones. CONCLUSIONS: Within the limits of the present study, the adequacy of histometrical observations under CLSM reveal commensurable information about soft-tissue-bone-implant details, when compared to traditional light microscopy histological protocols. The CLSM investigation may seem demanding, yet the richness of data acquired may justify this approach, provided seatbacks caused by improper manipulation of "thick" sections are avoided.

The Treatment of Severe Periodontitis Using a Local Antiseptic Desiccant and Subgingival Mechanical Instrumentation: A Pilot Study.

This randomized, split-mouth, controlled clinical study assessed the additional clinical benefits of a local desiccant antimicrobial agent (HY) combined with subgingival mechanical instrumentation (SRP) vs. SRP alone in treating severe periodontitis. Patients with stages III and IV periodontitis received full-mouth periodontal examinations at baseline and after a three-month follow-up. Two randomly selected hemiarches in each periodontitis patient were treated with SRP plus HY and were included in the test group, while the other two hemiarches received only SRP and were included in the control group. In thirty patients, the analyses of the evolution of the periodontal parameters over time showed statistically significant mean differences for the probing depths and clinical attachment level values resulting from all the examined sites, as well as from the interproximal sites (p < 0.001) in both the test and control groups. The intergroup comparisons of the same four parameters showed no significant differences (p = 0.322, p = 0.36, p = 0.516, and p = 0.509, respectively). Based on these study results, no additional benefits were obtained after HY subgingival applications.

Histomorphometrical and CBCT Evaluation of Tissue Loss Progression Induced by Consecutive, Alternate Ligatures in Experimental Peri-Implantitis in a Dog Model: A Pilot Study.

OBJECTIVES: Soft and hard tissue breakdown was histologically and radiologically assessed around implants with alternate, consecutively placed ligatures on the same edentulous dog hemimandible. The influence of ligatured implants (LI) on adjacent non-ligatured implants (NLI, as a possible naturally induced peri-implantitis) was also evaluated. MATERIAL AND METHODS: Three months after tooth extraction, five dental implants were placed in the dog hemimandible. Two months after abutment placement, ligatures were placed subsequently two months apart on alternate implants, while both intermediate implants were left without ligatures. Ligatures were kept in place during the entire experiment, and no plaque control measures were taken. Eleven months post-implantation, the animal was sacrificed. Undecalcified ground sections were cut, stained with Masson Goldner and MOVAT Pentachrome and evaluated by light microscopy. Soft and hard tissue loss was assessed using histomorphometric and CBCT parameters. RESULTS: All NLI presented deep false peri-implant pockets on the oral aspect and pronounced vertical bone resorption on the buccal aspect. After 2, 4 and 6 months, during the breakdown period, more than 30% of the bone was lost in LI in all directions, while, despite immediate vicinity, NLI displayed less destruction. Intense inflammation, typical for induced peri-implantitis, was present, with similar intensity in LI as NLI, but in different parts of the lesions. Morphometry confirmed intense soft tissue inflammation, more bone resorption and higher amounts of infiltrated connective tissue in LI when compared with NLI. CONCLUSION: Within the limits of the present pilot study, the adequacy of the experimental dog model based on ligature-induced peri-implantitis was able to be successfully challenged by non-ligature models of spontaneously occurring peri-implant inflammation, while meeting the requirements for experimental designs with a very small numbers of animals. The influence of implants with severe peri-implantitis on adjacent implants resulted in less than expected tissue loss in the latter accession numbers.

Mild systemic inflammation has a neuroprotective effect after stroke in rats.

Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia. To test this hypothesis, marginal periodontitis was induced by ligatures on the second maxillary molars in BB/LL Wistar rats for 3 weeks. Two weeks after periodontitis initiation, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery. After a survival time of 7 days after ischemia, rats were killed and bone loss was determined on the buccal and palatinal surfaces of the defleshed jaw. In addition, markers of systemic inflammation were determined in a different group of laboratory animals at 14 days after the onset of periodontitis. The infarct size and markers of the inflammatory reaction in the brain were determined by immunohistochemistry. We found: (i) rats with ligatures exhibited significantly more periodontal bone loss than the control rats; (ii) the development of periodontitis was associated with an elevated gene expression for several markers of systemic inflammation (interleukin-10, transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-1beta and interferon gamma; (iii) rats with periodontitis and a mild systemic inflammation had a significantly reduced infarct volume and a significant reduction in the number of brain macrophages in the infarcted area. In conclusion we found that mild systemic inflammation elicited prior to stroke onset may have a neuroprotective effect in rats by reducing the infarct volume and tissue destruction by brain macrophages.