PHILEOS (haemoPHILia and ostEoporOSis) Study: protocol of a multicentre prospective case–control study

Abstract

IntroductionTwo meta-analyses showed lower bone mineral density (BMD) in patients with haemophilia (haemophilia type and severity were often not specified) compared with healthy controls. This finding could be related to reduced mobility and sedentary lifestyle, and/or hepatitis C or HIV infection. The aim of this study is to determine osteoporosis prevalence in patients with haemophilia classified in function of the disease type (A or B) and severity, and to evaluate the potential role of regular prophylactic factor replacement (early vs delayed initiation) in preserving or restoring BMD.Methods and analysisThe haemoPHILia and ostEoporOSis Study is a prospective, controlled, multicentre study that will include patients in France (13 haemophilia treatment centres), Belgium (1 centre) and Romania (1 centre). In total, 240 patients with haemophilia and 240 matched healthy controls will be recruited (1:1). The primary objective is to determine osteoporosis prevalence in patients with severe haemophilia A and B (HA and HB) without prophylaxis, compared with healthy controls. Secondary outcomes include: prevalence of osteoporosis and osteopenia in patients with mild, moderate and severe HA or HB with prophylaxis (grouped in function of their age at prophylaxis initiation), compared with healthy subjects; BMD in patients with HA and HB of comparable severity; correlation between BMD and basal factor VIII/IX levels and thrombin potential; and quantification of plasmatic markers of bone remodelling (formation and resorption) in patients with haemophilia.Ethics and disseminationThe protocol was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2019-A03358-49). The results of this study will be actively disseminated through scientific publications and conference presentations.Trial registration numberNCT04384341.

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

“…While haemophilia is a relatively rare condition, there is a high prevalence of low BMD (27‐69.5%) 8–10 and fracture (4‐37%), 25 which is comparable to the prevalence of widely recognised risk factors including hyperthyroidism (63% low BMD, 35% vertebral fracture) 32 coeliac disease (49% low BMD, 25% peripheral skeleton fracture) 33,34 and rheumatoid arthritis (20% low BMD, 36% vertebral fracture) 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 PHILEOS study is a multicentre prospective case‐control study that aims to evaluate bone health in adult PWH who are categorised by prophylaxis status and age at treatment initiation 37 . PHILEOS will provide data on whether absence of prophylactic therapy, delay in therapy initiation and severe disease increase osteoporosis risk, necessitating selective screening 37 .…”

“…The PHILEOS study is a multicentre prospective case‐control study that aims to evaluate bone health in adult PWH who are categorised by prophylaxis status and age at treatment initiation 37 . PHILEOS will provide data on whether absence of prophylactic therapy, delay in therapy initiation and severe disease increase osteoporosis risk, necessitating selective screening 37 . In addition, The Haemophilia Osteoporosis Registry (THOR), will assess BMD and other components of bone strength using DXA and high resolution peripheral quantitative computed tomography (HR‐pQCT) to identify the best window for bone density screening in PWH and what particular aspects of bone strength are compromised in this population 51 .…”

“…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.…”

“…37 PHILEOS will provide data on whether absence of prophylactic therapy, delay in therapy initiation and severe disease increase osteoporosis risk, necessitating selective screening. 37 In addition, The Haemophilia Osteoporosis Registry (THOR), will assess BMD and other components of bone strength using DXA and high resolution peripheral quantitative computed tomography (HR-pQCT) to identify the best window for bone density screening in PWH and what particular aspects of bone strength are compromised in this population. 51 Current haemophilia guidelines on osteoporosis screening and diagnosis are inadequate as there are limited data available to provide evidence-based recommendations.…”