Hypoxia-inducible factor (HIF): how to improve osseointegration in hip arthroplasty secondary to avascular necrosis in sickle cell disease

Many studies in the literature have been carried out to evaluate the various cellular and molecular processes involved in osteogenesis. Angiogenesis and bone formation work closely together in this group of disorders. Hypoxia-inducible factor (HIF) which is stimulated in tissue hypoxia triggers a cascade of molecular processes that helps manage this physiological deficiency. However, there still remains a paucity of knowledge with regard to how sickle cell bone pathology, in particular avascular necrosis, could be altered when it comes to osseointegration at the molecular level. Hypoxia-inducible factor has been identified as key in mediating how cells adapt to molecular oxygen levels. The aim of this review is to further elucidate the physiology of hypoxia-inducible factor with its various pathways and to establish what role this factor could play in altering the disease pathophysiology of avascular necrosis caused by sickle cell disease and in improving osseointegration. This review article also seeks to propose certain research methodology frameworks in exploring how osseointegration could be improved in sickle cell disease patients with total hip replacements and how it could eventually reduce their already increased risk of undergoing revision surgery. Cite this article: EFORT Open Rev 2019;4:567-575. DOI: 10.1302/2058-5241.4.180030