Abstract
Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ), numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates, nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Further, the cell architecture and expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP-related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.
Highlights
Background of bisphosphonate-related osteonecrosis of the jaw (BRONJ)Bisphosphonates (BP) are widely used in different benign and malignant diseases such as Paget’s disease, osteoporosis, multiple myeloma and bone metastases of breast or prostate cancer
2003, Marx et al and other international research groups have reported on a medication-associated osteonecrosis of the jaw and called it bisphosphonate-related osteonecrosis of the jaw (BRONJ) [1]
Various international research groups have attempted to analyze the pathophysiology of BRONJ [4,5,6,7]
Summary
Bisphosphonates (BP) are widely used in different benign and malignant diseases such as Paget’s disease, osteoporosis, multiple myeloma and bone metastases of breast or prostate cancer. 2003, Marx et al and other international research groups have reported on a medication-associated osteonecrosis of the jaw and called it bisphosphonate-related osteonecrosis of the jaw (BRONJ) [1]. Apart from the inhibitory effect of bisphosphonates (BPs) on osteoclasts and osteoblasts, nitrogen-containing BP in particular interacts with cell soft tissue cells such as fibroblasts and keratinocytes [10,11]. After local accumulation of BPs, and especially in combination with other cancer medications such as chemotherapeutics und angiogenesis blocker, BPs might directly affect the oral mucosa via tissue toxicity. This could lead to gingiva injury followed by bone exposition, the main clinical sign of BRONJ [12,13]. In advanced stages of disease, the jaw can be rebuilt by microvascular flaps, e.g., the osseocutaneous fibular flap [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
