Evaluation Of OPG/RANKL In Bone Tissue Marginal To ONJ Lesions

Objective: The aim of this study was to evaluate, by immunoistochemical analysis, changes occurring in bone tissue close to sites affected by Osteonecrosis of the Jaws (ONJ) in patients under treatment with biphosphonates for bone metastasis prevention. Method: 20 patients were selected, both affected by different kind of carcinoma (prostatic, mammary, mieloma) and under treatment with ZOMETA iv (zoledronic acid, 4mg/5mL). All patients showed ONJ at 3rd stage, according to AAOMS staging. In order to reduce the gravity of the osteonecrotic lesions, and according to Società Italiana di Patologia e Medicina Orale (SIPMO) guidelines, an excision of the osteonecrotic bone was performed, and contestually a biopsy of the marginal tissue was withdrawn. Histological and immunohistochemical analyses were perfomed on specimens to evidence morphological changing and to evaluate expression of OPG/RANKL, BMP2, BMP4, iNOS and VEGF. Result: The morphological aspects of ONJ is characterized by severe reduction of vascularized areas, even in marginal necrotic zone, with no vital bone, as well as large bone trabecular net in marginal zone. At highest magnification it is also possible to see the absence of osteoclasts corrugated border. Immunoistochemistry results show poor expression both of OPG and RANKL, so the relative value OPG/RANKL is near to 1. BMP2 and BMP4 are not expressed at all. iNOS expression is very high as value while VEGF expression is very low, even in marginal areas. Conclusion: ONJ morphological aspect merge with the one evidenced in literature. Interesting is the correlation with molecular expressions, showing a severe decrease in expression of the proteins involved in physiological bone remodeling, even in marginal areas, indicating the proposed treatment as a good method to reduce the worsening of ONJ lesions.