Cytoprotective effect of flavonoid‐induced autophagy on bisphosphonate mediated cell death in osteoblast

With rapid economic growth and further developments in medical science, the entry into the aging population is currently increasing, as is the number of patients with metabolic diseases, such as hypertension, hyperlipidemia, heart disease, and diabetes. The current treatments for metabolic bone diseases, which are also on the rise, cause negative side effects. Bisphosphonates, which are used to treat osteoporosis, inhibit the bone resorption ability of osteoclasts and during prolonged administration, cause bisphosphonate‐related osteonecrosis of the jaw (BRONJ). Numerous studies have shown the potential role of natural plant products as flavonoids in the protection against osteoporosis and in the influence of bone remodeling. Autophagy occurs after the degradation of cytoplasmic components within the lysosome and serves as an essential cytoprotective response to pathologic stress caused by certain diseases. In the present study, we hypothesized that the cytoprotective effects of flavonoids might be related to those associated with autophagy, an essential cytoprotective response to the pathologic stress caused by certain diseases, in osteoblasts. We demonstrated the cytoprotective effect of flavonoid‐induced autophagy against the toxicity of zoledronate and the induction of autophagy by flavonoids to support osteogenic transcription factors, leading to osteoblast differentiation and bone formation. Further studies are necessary to clarify the connections between autophagy and osteogenesis. It would be helpful to shed light on methodological challenges through molecular biological studies and new animal models. The findings of the current study may help to delineate the potential role of flavonoids in the treatment of metabolic bone disease.