Bone Mineral Density, Bone Remodeling Biomarkers, and Hemostatic Correlates in Hemophilia and von Willebrand Disease

Persons with hemophilia (PwH) have lower bone mineral density (BMD) and increased fracture risk, but data for persons with von Willebrand disease (PwVWD) are limited. Biological mechanisms underlying altered bone health in bleeding disorders remain poorly defined. Primary aim: compare total BMD among PwH, PwVWD, and healthy controls. Secondary aim: characterize bone remodeling biomarkers and examine associations between BMD and simultaneous thrombin-plasmin generation (STP). In a three-group, cross-sectional observational study of participants aged 5-45 years (34 PwH, 45 PwVWD, 30 controls), total BMD and bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry ; trabecular and cortical parameters were assessed by peripheral quantitative computed tomography ; serum procollagen type 1 N-terminal propeptide and C-terminal telopeptide of type I collagen were measured as markers of bone formation and resorption; and STP assays quantified coagulation and fibrinolytic activity. Associations with BMD Z-scores were evaluated using linear and multivariable regression. PwVWD had significantly lower BMD Z-scores compared with controls, while PwH showed a similar but nonsignificant trend. Both PwH and PwVWD had significantly lower BMC. In multivariable models, higher thrombin generation was associated with higher BMD Z-scores, whereas higher plasmin generation was associated with lower BMD Z-scores. In multivariable models, STP parameters were associated with BMD and accounted for a greater proportion of variance than models including clinical factors or bone turnover markers. PwH and PwVWD exhibit measurable deficits in bone health. Observed associations between thrombin-plasmin dynamics and BMD are hypothesis-generating and support further longitudinal and mechanistic studies of hemostasis-bone relationships.