Abstract
Medication-related osteonecrosis of the jaws (MR-ONJ) is one of the most relevant side effects of bisphosphonate therapy; it is clinically defined as a non-healing wound in combination with an avascular and necrotic jaw within ongoing bisphosphonate therapy or after completed bisphosphonate therapy. Different theories concerning the development of MR-ONJ have been reported, while the exact pathophysiology is still unknown. Recent studies have increasingly focused on angiogenesis and revascularization concerning MR-ONJ pathophysiology, which seems to be a relevant factor in the development of MR-ONJ and a possible and promising point of action for MR-ONJ prevention and therapy. Therefore, and with respect to the different aspects and specific forms of angiogenesis, the enclosed review summarizes the possible role of angiogenesis and revascularization in the pathophysiology of MR-ONJ. Special focus is given to the strong negative influence of bisphosphonates on progenitor and mature endothelial cells in vitro as well as on microvessel sprouting in vitro and in vivo, which might result in overall reduced wound healing of oral soft and hard tissues, and therefore in an exposed and avascular jaw from a clinical viewpoint. Further, it will be summarized whether and in what way the aspect of angiogenesis might be used for possible MR-ONJ prevention and therapy.
Highlights
Bisphosphonates represent one of the most important and most clinically relevant antiresorptive agents in various fields of medicine and especially oncology
These two in vitro studies gave evidence that Medication-related osteonecrosis of the jaws (MR-ONJ) development may be caused by the negative influence of bisphosphonates on progenitor and mature endothelial cells—on the one hand from bisphosphonates in the circulating blood and on the other hand from bisphosphonates released from the local jaw—which might result in decreased wound healing of the soft tissues as well as in an avascular jaw
The findings demonstrated that GGOH cell treatment was able to reverse the strong negative effects of the tested bisphosphonates on human umbilical cord vein endothelial cells (HUVEC) cells and angiogenesis and revascularization in vitro [24]
Summary
Bisphosphonates represent one of the most important and most clinically relevant antiresorptive agents in various fields of medicine and especially oncology. Other popular theories describe an influence on oral soft tissues and inflammatory reactions In this context, oral soft tissue cells, especially gingival fibroblasts and oral keratinocytes, might be directly damaged by bisphosphonates, potentially resulting in a non-healing wound or uncovered, exposed jaw bone. Oral soft tissue cells, especially gingival fibroblasts and oral keratinocytes, might be directly damaged by bisphosphonates, potentially resulting in a non-healing wound or uncovered, exposed jaw bone This process might be triggered and enhanced by local inflammation, most likely caused by high local bisphosphonate concentrations in the jaw bone and the surrounding soft tissues. Different bacteria, such as actinomycetes, have been detected in ONJ specimens, which might have an influence on MR-ONJ development. The most relevant articles concerning the aspect of angiogenesis and MR-ONJ development within the time frame of 2015 to 2016 are summarized
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