Risk of osteoporotic fractures as a consequence of haemophilia: A nationwide population‐based cohort study

Abstract

Aim: Low bone mineral density occurs more commonly in patients with haemophilia (PWH) than the general population. However, the risk of haemophilia-related osteoporotic fractures has not been well established. We aim to explore the relationship between haemophilia and the development of osteoporotic fractures following haemophilia. Methods:This was a nationwide population-based cohort study based on the data in the Taiwan National Health Insurance Research Database (TNHIRD). Patients who were diagnosed with haemophilia were selected. A comparison cohort was formed of patients without haemophilia who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of new-onset osteoporotic fractures were calculated for both cohorts. Results:The haemophilia cohort consisted of 75 patients, and the comparison cohort comprised 300 matched control patients without haemophilia. The risk of osteoporotic fractures was higher in the haemophilia cohort than in the comparison cohort (HR = 5.41, 95% confidence interval [CI] = 2.42-12.1, P < 0.001). After adjustments for age, sex, comorbidities, urbanizations and socio-economic status, PWH were 4.37 times more likely to develop osteoporotic fractures (95% CI = 1.88-10.17, P = 0.001) as compared to matched cohort. In addition, the incidence of newly diagnosed osteoporotic fractures was significantly increased after 5-year follow-up durations.Conclusion: Though our study by TNHIRD presented methodologic flaws by its design nature, we observed that haemophilia may increase the risk of osteoporotic fractures and the cumulative incidence was significantly higher for PWH diagnosed more than 5 years. Clinicians should pay particular attention to osteoporotic fractures following haemophilia in PWH as they age. K E Y W O R D S cumulative incidence, haemophilia, National Health Insurance Research Database, osteoporotic fracture | 877 TUAN eT Al.

Osteoporosis management and falls prevention in patients with haemophilia: Review of haemophilia guidelines

“…35,36 This suggests that routine osteoporosis screening may be appropriate for certain groups of PWH (disease severity, adherence and type of prophylaxis, and age); data from the PHILEOS Study will inform on which group of PWH will benefit most from osteoporosis screening. 37 The majority of fractures within the general population occur in those aged over 65 years 24 ; in contrast, the majority of fractures in PWH occur much earlier, with 81% occurring below the age of 50 years (factor replacement therapy status unknown), 38 and 23-75% occurring below the age of 35-36 years (factor replacement therapy status unknown). 24,39 Minimal trauma fractures have also been reported in children with haemophilia, with one study reporting 4 out of 22 fractures occurring in children aged 14 and 15 years who had on demand therapy.…”

“…23 Concerningly, the haemophilia population is under-screened with a study finding that 92% of PWH were diagnosed with osteoporosis at the same time they were diagnosed with fracture (factor replacement therapy status unknown). 24 There is no consensus as to what age osteoporosis screening should take place in PWH, with studies suggesting screening in childhood, 15,41 early adulthood, 16,42 > 40 years 43 and > 50 years of age, unless clinical risk factors present earlier. 44 Notably, these recommendations are based on BMD and prevalence of fracture in PWH, as there are no longitudinal data on the utility and effectiveness of osteoporosis screening.…”

“…A 10‐year retrospective cohort study of 382 men with haemophilia found that PWH have a higher prevalence of fractures compared with the general population (24.8 vs 9.6 fractures per 1000 patient‐years, mean age 23 years, factor replacement therapy status unknown) 23 . Likewise, a population‐based cohort study ( n = 75, mean age 35.7 years, factor replacement therapy status unknown) found that PWH are at 4.37 times greater risk of osteoporotic fractures than controls 24 . The fracture prevalence in PWH is reported to range from 4% to 37%, 25 with one study reporting the combined prevalence of hip, vertebral and peripheral skeleton fractures as 16% in PWH ( n = 104, mean age 45.9 years) 8 – significantly higher than the 0.1% fracture prevalence found in the general population of a similar age from the same region 26 .…”

“…23 Likewise, a population-based cohort study (n = 75, mean age 35.7 years, factor replacement therapy status unknown) found that PWH are at 4.37 times greater risk of osteoporotic fractures than controls. 24 The fracture prevalence in PWH is reported to range from 4% to 37%, 25 with one study reporting the combined prevalence of hip, vertebral and peripheral skeleton fractures as 16% in PWH (n = 104, mean age 45.9 years) 8 -significantly higher than the 0.1% fracture prevalence found in the general population of a similar age from the same region. 26 In the general population, hip fractures in older adults have a high mortality, with 15% of patients dying during their initial hospital presentation and one third not surviving past 1-year post-fracture.…”

Low Bone Mineral Density in Hemophiliacs

“…In a study of young adults (median age 41.5 years), as many as 70% of patients with hemophilia exhibited decreased BMD, with 43% displaying osteopenia and 27% osteoporosis (15). Although the risk of hemophilia-related osteoporotic fractures has not been well-established, there are a few studies showing a higher fracture incidence in hemophilic subjects compared to the control population (16)(17)(18)(19).…”