New study finds lower bone density among people with VWD
Blood-clotting measures were linked to bone health in bleeding disorders
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People with von Willebrand disease (VWD) had lower bone mineral density than healthy individuals in a small, single-center study, highlighting the need to consider targeted bone health assessments for some patients.
The study also found that lower bone mineral density was associated with lower overall thrombin generation, reflecting reduced clot-forming activity, and higher overall plasmin generation, reflecting increased clot-dissolving activity, across the study group.
Researchers called for further work to clarify the mechanisms linking blood-clotting activity and bone health in inherited bleeding disorders, including VWD.
The study, “Bone Mineral Density, Bone Remodeling Biomarkers, and Hemostatic Correlates in Hemophilia and von Willebrand Disease,” was published in Blood Advances.
Study explores VWD, bone density
VWD is a bleeding disorder that affects the blood’s ability to clot properly. It’s caused by missing or dysfunctional von Willebrand factor (VWF), a protein that helps platelets, the cell fragments essential for clotting and healing, stick together and stop bleeding.
Little is known, however, about whether VWF affects bone health. In comparison, people with hemophilia, another bleeding disorder, are known to have lower bone mineral density (BMD, a measure of the amount of calcium and other minerals in bone) and a higher risk of fractures.
The study included 109 participants, ages 5 to 45, at the Arkansas Center for Bleeding Disorders. Among them, 45 had VWD, mostly type 1 (87%), followed by type 2 (7%) and type 3 (7%). Of the remaining participants, 34 had hemophilia type A or B, and 30 were healthy individuals who served as controls. Most participants with VWD were female, whereas all those with hemophilia were male.
Among participants who completed imaging, bone health was assessed with dual-energy X-ray absorptiometry (DEXA), which uses low-dose X-rays to measure total BMD and bone mineral content (BMC, the amount of mineral matter in bone and an indicator of skeletal health).
Results showed significantly lower BMD scores in people with VWD than in controls. While people with hemophilia showed a similar trend toward lower BMD, the difference did not reach statistical significance, meaning it could have occurred by chance. No statistically significant difference in BMD was found between people with VWD and hemophilia.
Likewise, people with VWD and hemophilia had significantly lower BMC scores than controls, with no meaningful differences between the patient groups. Additionally, people with VWD and hemophilia showed age-related declines in BMD and BMC scores.
When the researchers used a specialized CT scan to examine the forearm’s trabecular bone, the spongy tissue inside some bones, main group comparisons found no statistically significant differences between groups. No differences were noted in blood markers of bone formation and bone breakdown.
Blood-clotting measures tied to bone health
The team performed a specialized test called the simultaneous thrombin and plasmin generation (STP) assay to assess clotting and clot-dissolving activity from a blood sample. STP measures thrombin, an enzyme involved in blood clot formation, and plasmin, the primary enzyme responsible for dissolving blood clots.
Across combined STP measurements, lower BMD was associated with lower overall thrombin generation, reflecting reduced clot-forming activity, and higher overall plasmin generation, reflecting increased clot-dissolving activity.
To explain these findings, the researchers noted evidence indicating that “reduced thrombin signaling may impair bone formation, while increased plasmin activity may enhance bone turnover and resorption.”
Moderate physical activity was associated with higher BMD and BMC scores, with further gains seen at higher activity levels.
“This study demonstrates that [hemophilia] and [VWD patients] experience deficits in bone health compared with healthy controls, with particularly striking findings in [VWD],” the researchers concluded.
“These results support consideration of targeted bone health assessment in patients with inherited bleeding disorders who have additional clinical risk factors, while underscoring the need for longitudinal and subtype-specific studies to assess need for routine screening in [hemophilia] and [VWD],” the team added.
The researchers noted that the study was modest in size, cross-sectional, mostly White, and conducted at a single center, which may limit generalizability. They also noted that most participants with VWD had type 1 disease, meaning the findings should not be generalized across all VWD subtypes.
