Matteo Biasotto

Bone Scintigraphy and SPECT/CT of Bisphosphonate-Induced Osteonecrosis of the Jaw

Endovenous bisphosphonate therapy seems associated with osteonecrosis of the jaw. The aim of this study was to evaluate the additional diagnostic value of hybrid SPECT/CT in 99mTc-methylene diphosphonate 3-phase bone scintigraphy of osteonecrosis of the jaw in bisphosphonate-treated patients. Methods: We studied 15 patients (12 women and 3 men) with extraoral tumors affected by lytic bone metastases and multiple myeloma. All patients were previously treated with intravenous bisphosphonates (zoledronic acid) for 1–3 y, were negative for dental disease at clinical examination, and had suspected osteonecrosis of the jaw. All 15 patients underwent panoramic x-ray orthopantomography, CT or MRI (or both), microbiologic examination, 3-phase bone scintigraphy, and SPECT/CT of the maxillary region. Results: Three-phase bone-scintigraphy showed increased perfusion and an increased blood pool in 9 of 12 and 10 of 12 patients, respectively; at the metabolic phase, SPECT was positive in all patients and showed abnormal hyperactivity in the maxilla of 2 patients, in the mandible of 9 patients, and in both the mandible and the maxilla of 4 patients. Hybrid SPECT/CT was of particular value in 8 of 15 patients, allowing discrimination of the osteonecrotic core from nearby hyperactivity due to viable bone. Whole-body scintigraphy showed remote and multiple metastases in all patients. Orthopantomography showed nonspecific bone rarefaction in all patients but was not able to aid diagnosis of osteonecrosis of the jaw. CT and MRI showed anomalies in all symptomatic patients: CT was helpful in evaluating both cortical and trabecular bone aspects, and MRI was able to detect soft-tissue involvement but not cortical bone destruction. Conclusion: In appropriately selected oncology patients treated with bisphosphonates, an increased uptake of 99mTc-methylene diphosphonate in maxillary bones may suggest probable osteonecrosis of the jaw. In such cases, SPECT/CT may be of value in increasing the diagnostic accuracy of bone scanning, providing a precise functional anatomic correlation for the definition of the extent of disease.

A systematic review of therapeutical approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ)

OBJECTIVES The clinical management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains controversial. Since universally accepted guidelines have not been released yet, clinicians usually chose the type of treatment according to position papers based on expert opinion, or on empirical experience. The aim of this systematic review is to identify different therapeutical approaches for BRONJ that have been described in literature and to describe their effectiveness. MATERIALS AND METHODS A Medline via Pubmed and Scopus database literature search was conducted and all publications fulfilling the inclusion and exclusion criteria were included in eligibility assessment. The full texts of 146 retrieved articles were then screened and 40 studies were included in the quality assessment process. RESULTS After quality assessment, 22 full text articles were selected for the final review. 14 articles out of 22 were screened for stage-related outcomes. The overall outcome results and results for every disease stage were the highest when patients were treated with extensive surgery or extensive laser assisted surgery.

A novel animal model to study non‐spontaneous bisphosphonates osteonecrosis of jaw

The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach.

Reduced Antigenicity of Type I Collagen and Proteoglycans in Sclerotic Dentin

Antigenic alterations to the dentin organic matrix may be detected by an immunohistochemical approach. We hypothesized that alterations in the antigenicity of type I collagen and proteoglycans occur in sclerotic dentin under caries lesions. Transverse sections were prepared from carious teeth in the sclerotic zone and normal hard dentin. A double-immunolabeling technique was performed on these sections, with anti-type I collagen and anti-chondroitin 4/6 sulfate monoclonal primary antibodies. We used gold-conjugated secondary antibodies to visualize the distribution of intact collagen fibrils and proteoglycans by high-resolution SEM. For sclerotic dentin, labeling densities were 19.57 ± 3.01/μm2 for collagen and 9.84 ± 2.62/μm2 for proteoglycans. For normal hard dentin, values were 35.20 ± 2.73/μm2 and 17.03 ± 1.98/μm2, respectively. Distribution of intact collagen fibrils and proteoglycans in sclerotic dentin was significantly lower than in normal hard dentin. Reductions in antigenicity from the organic matrix of sclerotic dentin under caries lesions raise concern about the potential of intrafibrillar remineralization.

Clinical aspects and management of bisphosphonates-associated osteonecrosis of the jaws

Objective. An increasing incidence of osteonecrosis of the jaws (ONJ) in patients treated with intravenous bisphosphonates has been reported in the literature. The aim of this study was to evaluate the clinical aspects, diagnostic investigations, and management of ONJ associated with bisphosphonates in a series of 12 patients. Method. Our patients included 1 asymptomatic and 11 symptomatic subjects. For the symptomatic patients, the osteonecrosis was diagnosed through histological investigations of exposed bone that showed avascular and necrotic tissue with inflammatory infiltrate. The patients were complaining of swelling, fever, and bone exposure involving the jaws. The asymptomatic patient presented as an occasional finding during a routine dental examination and the necrosis was confirmed on the basis of imaging investigations. Radiographic, scintigraphic, and microbiological examinations were carried out for all patients. Treatment included antibiotics, minor surgical interventions, and hyperbaric oxygen therapy. Results. The radiological investigations revealed osteolytic areas and the scintigraphy demonstrated increased bone metabolism. The microbiological analysis showed pathogenic micro-organisms in the majority of patients. Therapy was useful in obtaining short-term symptomatic relief. Conclusions. Histological, radiological, nuclear medicine, and microbiological investigations are important diagnostic tools for patients with bisphosphonates-associated osteonecrosis of the jaws. However, a long-term follow-up is necessary if we are to better understand the treatment outcome.

Beeswax as dental filling on a Neolithic human tooth

Evidence of prehistoric dentistry has been limited to a few cases, the most ancient dating back to the Neolithic. Here we report a 6500-year-old human mandible from Slovenia whose left canine crown bears the traces of a filling with beeswax. The use of different analytical techniques, including synchrotron radiation computed micro-tomography (micro-CT), Accelerator Mass Spectrometry (AMS) radiocarbon dating, Infrared (IR) Spectroscopy and Scanning Electron Microscopy (SEM), has shown that the exposed area of dentine resulting from occlusal wear and the upper part of a vertical crack affecting enamel and dentin tissues were filled with beeswax shortly before or after the individual’s death. If the filling was done when the person was still alive, the intervention was likely aimed to relieve tooth sensitivity derived from either exposed dentine and/or the pain resulting from chewing on a cracked tooth: this would provide the earliest known direct evidence of therapeutic-palliative dental filling.

Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study

Oral mucositis (OM) is a serious and acute side effect in patients with cancer who receive chemotherapy or radiotherapy, often leading to the suspension of therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an effect on patient survival. Among the various interventions proposed in OM management, laser therapy is becoming a recommended treatment option but has limitations due to its heterogeneous laser parameters. Here, we report on our successful clinical experience on the use of class IV laser therapy to treat OM induced by different chemotherapy regimens. To shed light on the mechanisms of action of laser therapy in improving OM resolution, we have developed an animal model of chemotherapy-induced OM, in which we compare the efficacy of the standard low-power laser therapy protocol with an innovative protocol, defined as high-power laser therapy. We show that high-power laser therapy is more effective than low-power laser therapy in improving OM lesion healing, reducing the inflammatory burden, and preserving tissue integrity. In addition, high-power laser therapy has been particularly effective in promoting the formation of new arterioles within the granulation tissue. Our results provide important insights into the mechanism of action of biostimulating laser therapy on OM in vivo and pave a way for clinical experimentation with the use of high-power laser therapy.

Extensive Dental Caries in Patients with Oral Chronic Graft-versus-Host Disease

The oral cavity is one of the sites most frequently affected by chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (alloHCT) and can be a significant source of patient morbidity due to both mucosal and salivary gland involvement. The development of dental decay is a potentially devastating oral complication that has only rarely been reported in the transplantation literature. The purpose of this study was to comprehensively characterize a cohort of patients with cGVHD who subsequently developed extensive dental caries. A retrospective case-record review was conducted for patients who had undergone alloHCT at Dana-Farber/Brigham and Womens Cancer Center between 1990 and 2010 and developed cGVHD-associated rampant dental decay. All patients underwent dental evaluation, involving soft and hard tissue examination and dental radiography, before and after alloHCT. Any dental caries diagnosed at the pre-alloHCT evaluation were treated definitively, such that all patients were considered free of caries at the time of admission for alloHCT. A total of 21 patients were identified, with a median time of cGVHD onset of 5.4 months (range, 2.2-18.5 months) after alloHCT. All patients were diagnosed with oral cGVHD, with 90% demonstrating mucosal involvement and 95% demonstrating salivary gland involvement. Post-alloHCT dental evaluation was performed at a median of 22 months (range, 4-81) after alloHCT, when 10 patients were diagnosed with gross caries and 8 patients had 4 or more affected teeth. Cervical and interproximal patterns of dental caries were frequently diagnosed. The proportions of patients with gross caries, one surface caries, and more than one surface caries (classified as 0, 1-3, and ≥4, respectively) were significantly higher after alloHCT than before alloHCT, with at least 50% of patients experiencing an increase. Patients with oral cGVHD who were free of caries at the time of transplantation developed extensive areas of cervical decay at a median of less than 2 years after alloHCT. This is the first comprehensive characterization of this severe late complication of alloHCT and oral cGVHD. Greater awareness by transplantation oncologists and dentists, as well as more aggressive preventive measures, are needed, as are further prospective studies to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of preventive interventions.

BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival.

Defects in the mitotic spindle checkpoint have been proposed to contribute to the chromosomal instability observed in human cancers, including oral squamous cell carcinoma (OSCC). BUBR1 is a key component of the spindle checkpoint, whose role in oral carcinogenesis still needs to be clarified.

Comparative experimental evaluation of guidewire use in urology.

OBJECTIVES To evaluate the characteristics and mechanical properties of five different guidewires principally used in urology to provide a guide to the best choice in every situation. This objective was achieved by performing mechanical tests on each guidewire and on the same guidewire in relationship to a real human ureter. Finally, the mechanical properties of a real human ureter were evaluated experimentally. METHODS Five different guidewires with a 0.035-in. external diameter were studied to determine their mechanical properties of interest: tip buckling, shaft permanent deformation, guide friction on the human ureter, and the force at which the tip perforated a real human ureter. RESULTS Nitinol guidewires with hydrophilic coating had the least dangerous tip in the tip buckling and tip piercing force tests and the lowest friction values on the friction guide test. The shaft of the polytetrafluoroethylene-coated guidewires was stiffer on the bending resistance and plastic deformation tests. CONCLUSIONS The ideal endourologic guidewire should be sufficiently flexible and lubricated to negotiate a tortuous ureter and pass possible obstructions. However, high strength against bending is also required when we need to pass a stent or catheter over a guidewire.