Prospective Biomarkers of Bone Metabolism in Hemophilia A

Prospective Biomarkers of Bone Metabolism in Hemophilia A

One of the major shortcomings in studying bone disease in hemophilia is the lack of fracture outcome data demonstrating the clinical significance of decreased BMD and altered bone biomarkers in the hemophilia population. This study demonstrates that PwH have an increased risk of fracture compared to the general population and that the issue of bone health will increase in importance as the PwH population ages.

This is a pilot study to determine the impact of factor replacement on bone biomarkers in up to 20 hemophilia A subjects. Subjects will be recruited over 1 year for the 5-day protocol.

Following a 72-hour washout period, factor levels and bone biomarkers will be followed before and after 50 units/kg replacement on Day 1 and 20 units/kg replacement on Day 3. Each subject can serve as their Figure 4. Fracture rates in PwH compared to historic controls.

Inclusion Criteria:

1. Males with a diagnosis of hemophilia A with a historic baseline FVIII level ≤ 2%.
2. Age > 16 years old
3. Currently using ADVATE as FVIII replacement therapy

Exclusion Criteria:

1. Subject or guardian is unwilling or unable to give written informed consent and/or assent
2. Joint or muscle bleeding within 2 weeks of Study Day 1
3. Presence of a current factor inhibitor (>0.6 BU/mL via Nijmegan-modified Bethesda assay)
4. Known collagen vascular bone disease.