Epigenetic Regulation in Fibrous Dysplasia of Bone: mirDYS Study.

Study Overview
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Brief Summary
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Fibrous dysplasia of bone is a rare congenital but non-hereditary disease caused by a post-zygotic activation mutation of the GNAS gene. Patients with fibrous dysplasia may present pain and bone complications (fractures, deformities..) related to their bone lesions. For undetermined reasons, severity and disease evolution may vary considerably from patient to patient. Epigenetic regulation could then be involved, including micro Ribonucleic Acids (miRs). These small non-coding micro Ribonucleic Acids are involved in the regulation of major steps of cellular processes in different pathologies, in particular in bone diseases. However, micro Ribonucleic Acids have never been studied in fibrous dysplasia. The aim of this study is to identify micro Ribonucleic Acids significantly associated with the severity of fibrous dysplasia.

Official Title
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Epigenetic Regulation of Activity and Severity of Fibrous Dysplasia in Bone: mirDYS Study.

Conditions
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Fibrous Dysplasia of Bone

Intervention / Treatment
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* Other: Blood sample
* Other: Waste bone tissue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Control population : men and women, 18 years-old and over, consulting a rheumatologist or an orthopedist for arthrosis have scheduled surgery for hip or knee replacement surgery or any intervention involving the lower limb or upper limb. Patients with Fibrous dysplasia: men and women, 18 years-old and over, with a diagnosis of fibrous dysplasia previously established by a rheumatologist. Exclusion Criteria: Refusal to participate in the study Long- term corticosteroids treatment (> 3 months) Treated osteoporosis Chronic inflammatory rheumatism (rheumatoid arthritis, psoriasic arthritis, spondyloarthropathy) Collagen disease (osteogenesis imperfecta…) Paget's disease, benign bone tumors Uncontrolled hypo/hyper-thyroidism, hypo/hyper-parathryoidism Severe renal impairment (GFR < 30 ml/min/1.73m2) Cancer or bone metastases (current or in the past two years) Paget disease, benign bone tumor (osteoid osteoma, enchondroma …) Malabsorptive disease (Celiac disease, Whipple's disease, intestinal bypass, short bowel syndrome) and inflammatory bowel disease Pregnant women or lactating Psychiatric disorders Difficulty in understanding French Not a beneficiary of french social security Patients protected by law

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monostotic fibrous dysplasia<br>Patients with monostotic Fibrous dysplasia. | Other: Blood sample<br>* A study specific blood sample will be collected.<br>Other: Waste bone tissue<br>* For 3 patients of each group, patients having a scheduled surgery, a piece of waste bone tissue will be collected after surgery.<br>|
| Experimental: Polyostotic fibrous dysplasia<br>Patients with polyostotic Fibrous dysplasia. | Other: Blood sample<br>* A study specific blood sample will be collected.<br>Other: Waste bone tissue<br>* For 3 patients of each group, patients having a scheduled surgery, a piece of waste bone tissue will be collected after surgery.<br>|
| Active Comparator: Controls<br>Control patients having a scheduled surgery for osteoarthritis. | Other: Blood sample<br>* A study specific blood sample will be collected.<br>Other: Waste bone tissue<br>* For 3 patients of each group, patients having a scheduled surgery, a piece of waste bone tissue will be collected after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of micro Ribonucleic acids expression in the serum | The objective is to identify specific microRibonucleic acids expressed in serum of patients using NGS (Next Generation Sequencing). | At inclusion | 
| Evaluation of micro Ribonucleic acids expression in the bone tissue | The objective is to identify specific micro Ribonucleic acids expressed in bone tissue obtained from surgery (patients having a scheduled surgery for osteoarthritis or fibrous dysplasia) using NGS (Next Generation Sequencing) | At inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of micro Ribonucleic acids expression | The objective is to compare nature and level of expression of the micro Ribonucleic acids identify by NGS (Next Generation Sequencing) in bone tissue and serum between the 3 groups of subjects: monostotic Fibrous Dysplasia, polyostotic Fibrous Dysplasia and controls (controls are patients with osteoarthritis). | Time of realization of the analyzes, an average of 6 months | 
| Validation of micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in blood samples | The objective is to validate expression of micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in blood samples of patients from 4 pre-existing cohorts : a fibrous dysplasia cohort (PERIOSDYS) and 3 cohorts of control patients (OFELY and MODAM for women, STRAMBO for men). For that the expression of the significant micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in sera of patients with monostotic and polyostotic fibrous dysplasia versus control patients will be measured by RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction) and then these results will be compared with same analysis on blood samples of patients from the 4 pre-existing cohorts. | Time of realization of the analyzes, an average of 6 months | 
| Association between micro Ribonucleic acids and severity of fibrous dysplasia. | Association between expression of significant micro Ribonucleic acids in patients with fibrous dysplasia with the severity of the disease will be studied by statistics analysis. Severity of fibrous dysplasia will be evaluated with clinical, biological and radiological data extracted from patients' medical records (Easily software) and from the CEMARA database (fibrous dysplasia database). | Time of realization of the analyzes, an average of 6 months |