Bone Health in Adults With Severe Haemophilia Receiving Different Prophylactic Treatments.

INTRODUCTION

Haemophilia, an X-linked disorder, is linked to reduced bone mineral density (BMD). Emicizumab, a factor VIII (FVIII) mimetic, provides a model to study the role of FVIII in bone health.

AIM: To evaluate BMD in adults with severe haemophilia under different prophylactic regimens, focusing on whether emicizumab maintains bone health comparable to FVIII prophylaxis.

METHODS

Forty male adults with severe haemophilia A or B were prospectively enrolled at a single centre (2019-2024) and assigned to five prophylactic groups: emicizumab (with/without inhibitors), FVIII, factor IX (FIX) or investigational agents. Annual assessments included dual-energy X-ray absorptiometry, joint status, mobility and bone turnover markers.

RESULTS

Of the 40 patients, 18 received FVIII, 10 FIX, 4 haemophilia A with inhibitors on emicizumab, 4 haemophilia A without inhibitors on emicizumab and 4 investigational therapies. At baseline, spine BMD z-scores were comparable to age-matched norms, whereas hip BMD was significantly lower (median -0.8; p < 0.001). After 1 year, spine and hip BMD changes did not differ significantly across treatment groups (p = 0.9010 and p = 0.8073, respectively). Lower annual bleeding rate, middle age and BMI extremes were associated with BMD improvement. Emicizumab-treated patients, with or without inhibitors, showed non-inferior BMD outcomes compared to those receiving FVIII, with all 95% confidence intervals within the predefined margin (±0.5).

CONCLUSION

BMD outcomes did not differ across regimens. Emicizumab was comparable to FVIII, suggesting bleed control, not factor replacement, is key to bone health in haemophilia.

PLAIN LANGUAGE SUMMARY: People with haemophilia often have problems with joint bleeding, which can limit movement and reduce bone strength. Different treatments are now available to prevent bleeding, including factor replacement and newer medicines such as emicizumab. It is not clear whether these treatments affect bone health differently. In this study, we followed 40 adults with haemophilia and measured their bone health for 1 year. We found that bone outcomes were similar across all treatment groups. Emicizumab worked just as well as factor VIII in maintaining bone strength. This means that good bleeding control may be the key to keeping bones healthy in haemophilia, regardless of the treatment type.