Bone Microarchitecture in Men With Hemophilia

Study Overview
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Brief Summary
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Hemophilia A and B are hereditary sex-linked deficiencies of coagulation factors VIII and IX characterized by bleeding. Their modern therapy increases life expectancy and risk of age-related diseases, e.g., osteoporosis. Hemophilia-specific risk factors impair formation of peak bone mass and accelerate bone loss. Fractures are more frequent in hemophilic men vs. age-matched men and induce bleeding which is aggravated by manipulations and surgical intervention. The hypothesis of this study is that hemophilic men have poor bone microarchitecture (assessed by High-resolution peripheral quantitative computed tomography (HR-pQCT)) related to an imbalance between bone formation and resorption (assessed by bone turnover markers (BTM) and bone biomarkers). The study aims to assess the difference in low trabecular number (Tb.N) at the distal radius between hemophilic men (cases) and age- height-weight-ethnicity and smoking-matched healthy men (controls). Correlation between BTM and Tb.N will be also studied. Biologic markers of bone remodeling (C-terminal telopeptide of type I collagen (PINP), N-terminal propeptide of type I procollagen (CTX-I), periostin) will be studied.

Official Title
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Bone Microarchitecture in Men With Hemophilia

Conditions
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Severe Hemophilia A, Osteoporosis

Intervention / Treatment
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* Radiation: HR-pQCT
* Biological: Blood sample
* Radiation: Dual energy X-ray absorptiometry
* Other: medical data collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: Men aged 20 to 60 years Severe hemophilia A or B (FVIII or FIX<1%) Regular followed up in Lyon Hemophilia Center Ability to give free and informed consent Person capable of actively participating in radiological examinations Healthy Mens: Aged 20 to 60 years Exclusion Criteria: Women Not covered by health system Vulnerable (adults unable to consent, protected under guardianship, prisoner) Any blood coagulation abnormality other than severe hemophilia A or B Having one of the following treatments against osteoporosis of more than 6 months : bisphosphonates, denosumab, teriparatide With a chronical disease having a high impact on bone structure and no related to hemophilia disease, such as Cushing or Crohn diseases.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: severe hemophilia A or B patients<br>30 patients with severe hemophilia A or B (Factor (F)VIII or Factor IX (FIX)≤ 1%) aged 20 to 60 years will be included in this study. | Radiation: HR-pQCT<br>* Patients will have a unique HR-pQCT scanner imaging to study their bone microarchitecture<br>Biological: Blood sample<br>* Patients will have a unique blood sampling of 10 mL for the measurements of sera PINP, CTX-I, periostin levels<br>Radiation: Dual energy X-ray absorptiometry<br>* A dual energy X-ray absorptiometry scan of lumbar spine, hip, distal radius and whole body, body composition, lateral spine will be performed.<br>|
| Other: healthy men<br>Data of healthy men, matching in age- height-weight-ethnicity and smoking-matched with patient will be collected. These data are already available at the Institut national de la santé et de la recherche médicale (INSERM) research unit associated. | Other: medical data collection<br>* Data of healthy men is already available<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of trabecular at distal tibia | The number of trabecular at distal tibia will be performed and compared to the values available for the healthy control group | 3 months following the inclusion | 
| number of trabecular at distal radius | The number of trabecular at distal radius will be performed and compared to the values available for the healthy control group | 3 months following the inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sera bone remodeling biomarkers | This biomarkers will be performed: PINP (ng/ml) CTX-1 (ng/ml) Periostin (ng/ml) | 3 months following the inclusion | 
| reflection of bone strength | Micro-Finite Element Analysis (µFEA) reflection of bone strength will be performed and compared to the values available for the healthy control group | 3 months following the inclusion | 
| Trabecular Bone Score (TBS) | Trabecular Bone Score (TBS) will be performed and compared to the values available for the healthy control group The trabecular bone score is a measure of bone texture correlated with bone microarchitecture and a marker for the risk of osteoporosis | 3 months following the inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia, osteoporosis, bone microarchitecture, bone remodeling