Bone and Hemophilia: The Role of Factor VIII-Systematic Review.

Factor VIII (FVIII) is involved in several molecular pathways and biological processes; indeed, it has a role in the coagulative cascade, cardiovascular disease, hypertension, brain and renal function, cancer incidence and spread, macrophage polarization, and angiogenesis. Hemophilic patients usually present an increase in fracture risk, bone resorption, and an excess of osteoporosis as compared to healthy individuals. Several studies have tried to clarify their etiology but unfortunately it is still unclear. This review focuses on the role of FVIII in bone biology by summarizing all the knowledge present in the literature. We carried out a systematic review of the available literature following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Several studies demonstrated that FVIII is involved in different molecular pathways interfering with bone physiology; it exerts interesting effects on OPG/RANK/RANKL pathways and thrombin/PAR1 pathways. These data confirm a relationship between FVIII and bone metabolism; however, there are still many aspects to be clarified. This review highlights the role of the coagulation factor FVIII in bone metabolism, suggesting new hypotheses for future studies both in vitro and in vivo to better understand the important pleiotropic role of FVIII and hopefully to develop new therapeutic agents for skeletal diseases.