Brief Report THROMBOSIS AND HEMOSTASIS Premature changes in trabecular and cortical microarchitecture result in decreased bone strength in hemophilia

With the increasing availability and affordability of safe factor concentrate replacement therapy, factor prophylaxis, and comprehensive care, persons with hemophilia (PWH) today should have a normal life expectancy, and more are living beyond age 65 years. However, comorbid complications associated with aging in this population are largely unknown, and background data on the clinical implications of these issues are lacking. Low bone mineral density (BMD) and associated osteoporosis is one of the emerging concerns that has been described, with an estimated prevalence of up to 70% in PWH. Although lowBMD is well described in PWH, data remains limited on fracture risk, with case series reporting fracture prevalence of 12% to 18%. Osteoporosis is a pathologic bone disorder characterized by low BMD and microarchitectural bone disruption that results in increased risk for fracture. The majority of studies investigating BMD in males with hemophilia have used areal BMD measurement by dual X-ray absorptiometry, which is unable to account for geometric differences affecting true volumetric BMD. Furthermore, dual X-ray absorptiometry provides no information on themicroarchitecture of the cortical and trabecular compartments that ultimately underpin bone strength. In this pilot study, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure true BMD and detect changes in cortical and trabecular bone microarchitecture (to an isotropic voxel size of 82mm)and used novelmicrofinite element analysis (mFEA) to assess the effect of skeletal alterations on bone strength compared with matched controls. Because inactivity and cytokineinduced bone mineral loss resulting from chronic hemophilic arthropathy are proposed mechanisms for BMD loss in PWH, Gilbert joint scores for severity of hemophilia arthropathy were measured for correlation analysis.