Oxygen is an essential element in the process of cellular oxidation, and hypoxia, a state of insufficient oxygen, can profoundly influence cellular adaptive responses through gene transcription, thereby impacting cell metabolism, angiogenesis, and inflammation. Hypoxia-inducible factor (HIF), particularly its alpha subunit (HIF-1α), is a critical transcription factor that orchestrates cellular adaptation to hypoxic environments and plays a multifaceted role in various cellular activities. In recent years, HIF-1α has been widely implicated in stimulating hematopoietic function and the good effect of roxadustat in treating renal anemia. However, the specific role of HIF-1α in bone metabolism remains unclear. More and more studies have shown that HIF-1α can not only directly affect osteoblasts, osteoclasts, osteocytes, and bone matrix during bone remodeling, but also locally and remotely regulate macrophages and various cytokines involved in bone remodeling. In addition, HIF-1α can indirectly regulate bone metabolism by promoting angiogenesis and regulating cell metabolism. This review comprehensively elucidates the intricate mechanisms by which HIF-1α influences bone metabolism. The aim is to provide a robust theoretical foundation for exploring the potential therapeutic application of roxadustat to improve bone metabolism in patients with Chronic Kidney Disease-related Osteoporosis (CKD-RO). It is important to note that, while this review highlights promising findings, the current evidence is primarily derived from preclinical animal studies and necessitates rigorous clinical validation.
Wang et al. (Fri,) studied this question.