Fracture Risk in People With Haemophilia A and B: A Systematic Review and Meta-Analysis.

Introduction: Haemophilia A and B is a disease consistently associated with reduced bone mineral density, both in adults and children. However, whether haemophilia also increases fracture risk has not yet been proven.

Aim: This systematic review and meta-analysis aimed to synthesize and analyse studies evaluating the association between haemophilia and fracture risk.

Methods: Comprehensive research was conducted in three electronic databases (PubMed, CENTRAL, and Scopus) up to 30 June 2024. Data were expressed as relative risk (RR) with 95% confidence intervals (CI). The I² index was employed to evaluate heterogeneity.

Results: Fourteen studies were included in the qualitative and four in the quantitative analysis (participants: 13,221, publication years: 2007-2022). Regarding design, five studies were retrospective cohorts, two were case-control, and seven were cross-sectional. Fracture prevalence in people with haemophilia (PWH) was 5.7%, ranging from 1.4% to 27.7% (data from 14 studies), compared with 0.9% in the control group, ranging from 0% to 5.1% (data from 3 studies). In comparison with healthy men, PWH demonstrated increased fracture risk (RR 4.56, 95% CI 1.28-16.25, p = 0.019, I² 90.74%). However, there was insufficient data to categorize fractures according to their location and to compare fracture incidence between patients receiving prophylaxis and those on-demand treatment, as well as according to the type or severity of haemophilia.

Conclusion: This is the first meta-analysis showing a more than 4-fold increased fracture risk in PWH compared with the general population.