Severe Hemophilia A, Osteoporosis
Conditions
Keywords
Hemophilia, osteoporosis, bone microarchitecture, bone remodeling
Brief summary
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.
Interventions
RADIATIONHR-pQCT
Patients will have a unique HR-pQCT scanner imaging to study their bone microarchitecture
BIOLOGICALBlood sample
Patients will have a unique blood sampling of 10 mL for the measurements of sera PINP, CTX-I, periostin levels
RADIATIONDual energy X-ray absorptiometry
A dual energy X-ray absorptiometry scan of lumbar spine, hip, distal radius and whole body, body composition, lateral spine will be performed.
Data of healthy men is already available
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| number of trabecular at distal tibia | 3 months following the inclusion | The number of trabecular at distal tibia will be performed and compared to the values available for the healthy control group |
| number of trabecular at distal radius | 3 months following the inclusion | The number of trabecular at distal radius will be performed and compared to the values available for the healthy control group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sera bone remodeling biomarkers | 3 months following the inclusion | This biomarkers will be performed: * PINP (ng/ml) * CTX-1 (ng/ml) * Periostin (ng/ml) |
| reflection of bone strength | 3 months following the inclusion | Micro-Finite Element Analysis (µFEA) reflection of bone strength will be performed and compared to the values available for the healthy control group |
| Trabecular Bone Score (TBS) | 3 months following the inclusion | 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 |
Countries
France
Outcome results
None listed