IADR Abstract Archives
Medication-Related Osteonecrosis of Jaw (MRONJ): An osteoclastic or inflammatory condition.
Objectives: The use of bisphosphonates in preventing skeletal-related events has significantly expanded in recent years because of the rising prevalence of osteoporosis and bone metastases. The incidence of the uncommon but potentially serious adverse effect of using bisphosphonates, known as MRONJ, has concurrently grown. The rarity of MRONJ limits the scope of human study, and the underlying mechanism is still unknown. There is strong support in the literature for an immunological role in the development of MRONJ. This study postulates that an additional inflammatory mechanism is required to generate MRONJ since bisphosphonate-induced osteoclastic inhibition alone is insufficient to create it.
Methods: This study measures and analyses osteoclast activity on the adult zebrafish's tooth-bearing ceratobranchial bone. We also characterised the changes to osteoclasts, osteoblasts, neutrophils, macrophages, NF-kB signalling pathway due to alendronate treatment, using various trangenic zebrafish.
Results: We discovered that bisphosphonate could suppress the spontaneous osteoclastic activity around the pharyngeal teeth of zebrafish. We also found teeth-bone disjunction in every adult zebrafish treated with bisphosphonates, which is identical to the MRONJ seen in the clinic. Zebrafish are, therefore, a reliable and practical model of MRONJ. In this investigation, we also demonstrated an initial neutrophil invasion that subsided after three weeks, followed by an accumulation of activated macrophages at the teeth-bone junction. An early downregulation of NF-kB signalling was present along with this, and at later time periods, a strong upregulation of NF-kB signalling was observed.
Conclusions: In conclusion, We developed a zebrafish model of MRONJ and used it to get some initial understanding of the role played by the immune system in the condition. We also discovered a signaling route that can be targeted for the treatment or prevention of MRONJ.
Methods: This study measures and analyses osteoclast activity on the adult zebrafish's tooth-bearing ceratobranchial bone. We also characterised the changes to osteoclasts, osteoblasts, neutrophils, macrophages, NF-kB signalling pathway due to alendronate treatment, using various trangenic zebrafish.
Results: We discovered that bisphosphonate could suppress the spontaneous osteoclastic activity around the pharyngeal teeth of zebrafish. We also found teeth-bone disjunction in every adult zebrafish treated with bisphosphonates, which is identical to the MRONJ seen in the clinic. Zebrafish are, therefore, a reliable and practical model of MRONJ. In this investigation, we also demonstrated an initial neutrophil invasion that subsided after three weeks, followed by an accumulation of activated macrophages at the teeth-bone junction. An early downregulation of NF-kB signalling was present along with this, and at later time periods, a strong upregulation of NF-kB signalling was observed.
Conclusions: In conclusion, We developed a zebrafish model of MRONJ and used it to get some initial understanding of the role played by the immune system in the condition. We also discovered a signaling route that can be targeted for the treatment or prevention of MRONJ.