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

IntroductionHaemophilia 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.AimThis systematic review and meta-analysis aimed to synthesize and analyse studies evaluating the association between haemophilia and fracture risk.MethodsComprehensive 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.ResultsFourteen 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.ConclusionThis is the first meta-analysis showing a more than 4-fold increased fracture risk in PWH compared with the general population.