Evaluation of the immune state activation in patients affected by ONJ: preliminary data

Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) is a serious adverse event characterized by non-healing necrotic bone tissue of mandible or maxilla. BPs target osteoclasts, inhibiting their action and blocking bone resorption, nonetheless an increased bone resorption in the oral cavity is associated to ONJ. One of the causes of ONJ is the dysregulation of the immune system, in particular the strong reduction of gamma/delta T cells circulating in peripheral blood (PB). The rate of circulating osteoclast precursors (OCPs) is altered in bone metastatic patients, suggesting a systemic alteration of osteoclast compartment, but we do not know wether it is altered in cancer patients affected by active lesion of ONJ induced by Zoledronic acid treatment. By flow cytometric analysis of patients' and controls' PB cells, we studied the presence of different T cell subsets, according to the expression of gamma/delta chains, CD4, CD8, CD25 and CD69 and of OCPs. We also evaluated the capability of PBMCs to spontaneously differentiate into osteoclasts in vitro, which is an index of pathological bone resorption. Our preliminary results confirmed in ONJ patients a marked reduction in gamma/delta T cells compared to their level befor patients started BP treatment. The subsets of activated T cells and OCPs were not significantly modified. In ONJ patients, in vitro osteoclastogenesis was comparable to the one of healthy control, while before patients started BP treatment osteoclastogenesis was significantly increased. This result suggests that BPs correctly act in reducing the systemic activation of osteoclasts, associated to bone metastatic patients, as expected, but BPs fail to block osteoclast activity locally

Tooth loss and obstructive sleep apnoea

BACKGROUND: Complete tooth loss (edentulism) produces anatomical changes that may impair upper airway size and function. The aim of this study was to evaluate whether edentulism favours the occurrence of obstructive sleep apnoea (OSA). METHODS: Polysomnography was performed in 48 edentulous subjects on two consecutive nights, one slept with and the other without dentures. Upper airway size was assessed by cephalometry and by recording forced mid-inspiratory airflow rate (FIF50). Exhaled nitric oxide (eNO) and oral NO (oNO), were measured as markers of airway and oropharyngeal inflammation. RESULTS: The apnoea/hypopnoea index (AHI) without dentures was significantly higher than with dentures (17.4 +/- 3.6 versus 11.0 +/- 2.3. p = 0.002), and was inversely related to FIF50 (p = 0.017) and directly related to eNO (p = 0.042). Sleeping with dentures, 23 subjects (48%) had an AHI over 5, consistent with OSA, but sleeping without dentures the number of subjects with abnormal AHI rose to 34 (71%). At cephalometry, removing dentures produced a significant decrease in retropharyngeal space (from 1.522 +/- 0.33 cm to 1.27 +/- 0.42 cm, p = 0.006). Both morning eNO and oNO were higher after the night slept without dentures (eNO 46.1 +/- 8.2 ppb versus 33.7 +/- 6.3 ppb, p = 0.035, oNO 84.6 +/- 13.7 ppb versus 59.2 +/- 17.4 ppb, p = 0.001). CONCLUSION: These findings suggest that complete tooth loss favours upper airway obstruction during sleep. This untoward effect seems to be due to decrease in retropharyngeal space and is associated with increased oral and exhaled NO concentration