Osteoporosis is associated with X-linked genetic disease, particularly in males.138,139 Osteoporosis and low bone mass are prevalent comorbidities in hemophilia A (HA), a congenital X-linked recessive genetic disease.140–143 The high prevalence of osteoporosis in HA patients has been reported to be closely associated with VD deficiency and hemophilic arthropathy.144,145 In HA patients, the missing or defective expression of factor VIII (FVIII) disturbs bone homeostasis via the RANK/RANKL/osteoprotegerin (OPG) axis. This evidence concerns the gene TNFRSF11B and osteoporosis.