99Tc(m)-MDP three-phase bone scans who could be used as a screening test to detect subclinical osteonecrosis in patients who have received bisphosphonates. CT scans and MRI are useful in defining the features and extent of osteolytic lesions.

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 99m Tc-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 bonescintigraphy 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 99m Tc-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.

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.

NGF peptide and tryptase activity were shown to be significantly and persistently higher in saliva of BMS subjects, with respect to control values. Conversely the salivary levels of SP were shown to be significantly lower, while neutrophil markers didn't show any change. We conclude that the neuropathic origin of the disease is confirmed at salivary level. Furthermore, the higher tryptase activity indicates a possible involvement of mast cells. The salivary neuropeptide concentration in BMS subjects, together with mast cell derived compounds, could be useful biomarkers for diagnosis and monitoring of this disease.

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.