The hypoxia pathway not only regulates the organism to adapt to the special environment, such as short-term hypoxia in the plateau under normal physiological conditions, but also plays an important role in the occurrence and development of various diseases such as cancer, cardiovascular diseases, osteoporosis. Bone, as a special organ of the body, is in a relatively low oxygen environment, in which the expression of hypoxia-inducible factor (HIF)-related molecules maintains the necessary conditions for bone development. Osteoporosis disease with iron overload endangers individuals, families and society, and bone homeostasis disorder is linked to some extent with hypoxia pathway abnormality, so it is urgent to clarify the hypoxia pathway in osteoporosis to guide clinical medication efficiently. Based on this background, using the keywords “hypoxia/HIF, osteoporosis, osteoblasts, osteoclasts, osteocytes, iron/iron metabolism”, a matching search was carried out through the Pubmed and Web Of Science databases, then the papers related to this review were screened, summarized and sorted. This review summarizes the relationship and regulation between the hypoxia pathway and osteoporosis (also including osteoblasts, osteoclasts, osteocytes) by arranging the references on the latest research progress, introduces briefly the application of hyperbaric oxygen therapy in osteoporosis symptoms (mechanical stimulation induces skeletal response to hypoxic signal activation), hypoxic-related drugs used in iron accumulation/osteoporosis model study, and also puts forward the prospects of future research.