Abstract
Osteopenia and osteoporosis have increasingly become a recognized morbidity in those persons with hemophilia (PwH) receiving inadequate prophylactic clotting factor replacement. Animal models can control or eliminate genetic and environmental factors and allow for invasive testing not clinically permissible. Here, we describe the skeletal phenotype of juvenile and adult male mice with a genetically engineered deficiency in coagulation factor IX (FIX KO). Although the somatic growth of FIX KO mice matched that of their wild-type (WT) littermates at 10 and 20 weeks of age, the FIX KO mice displayed reduced bone mineral density (BMD), reduced cortical and cancellous bone mass, and diminished whole bone fracture resistance. These findings coupled with parallel observations in a murine model of hemophilia A (FVIII deficiency) point to an effector downstream of the coagulation cascade that is necessary for normal skeletal development. Further study of potential mechanisms underlying the bone disease observed in rare clotting factor deficiency syndromes may lead to new diagnostic and therapeutic insights for metabolic bone diseases in general.