Bone represents a well vascularized structure which is remodelled and renewed continuously. It consists of osteoblasts, osteoclasts and osteocytes which have a precise role in the context of endochondral and intramembranous ossification. While the link between the bone tissue, bone marrow and the haematopoiesis is crucial for the generation of progenitor bone forming cells, recent research indicates that bone physiology as well as bone healing, repair and regeneration is directly dependent on bone angiogenesis. Experimental research suggest that angiogenesis and osteogenesis are directly coupled through a mechanism in which type H endothelial cells have a role of paramount importance. Apart from type H endothelial cells, other molecular elements such as HIF and Notch as well as CD31-endomucin capillaries and miR-497∼195 endothelial clusters may have a significant role in angiogenesis-osteogenesis coupling. The number of type H endothelial cells decreases significantly in elderly and is paralleled by a significant drop in the supply of progenitor cells. This would explain the bone loss and the decreased bone regeneration potential seen in elderly patients. Overall, it is suggested that endothelial cells and bone angiogenesis would represent therapeutic targets in various pathological conditions characterized by bone loss and impaired regeneration.
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.
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