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Diagnosis of Osteogenesis Imperfecta in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03169192
Recruitment Status : Unknown
Verified May 2017 by mohamed aboubakr mohamed, Assiut University.
Recruitment status was:  Not yet recruiting
First Posted : May 30, 2017
Last Update Posted : May 30, 2017
Information provided by (Responsible Party):
mohamed aboubakr mohamed, Assiut University

Brief Summary:

The study will be conducted at Assiut university children hospital and it will include patients with history of repeated fractures due to mild or irrelevant trauma.

Diagnosis will be established by biochemical tests, bone survey to exclude secondary causes followed by Dual Energy absorbiometry scan to detect bone density of selected cases then confirm our diagnosis by detection of gene mutations of Osteogenesis imperfecta during one and half year duration with starting zoledronic acid therapy during this duration.

Condition or disease Intervention/treatment
Bone Disease, Metabolic Drug: Zoledronic Acid

Detailed Description:

Osteogenesis imperfecta is a genetic disorder of the connective tissue matrix caused by abnormal collagen microfibril assembly, .Several clinical subtypes of Osteogenesis imperfecta have been described based on the clinical, biochemical, and molecular nature of the disorder . New research is emphasizing the structural interaction within the microfibril and identifying regions within the collagen, which play greater or lesser roles in the structural properties of the triple helix, .In taking this information into account, clinical phenotypes resulting from certain mutations can be predicted because of this pathogenetic correlation.

The clinical manifestations vary considerably, ranging from a severe perinatal lethal form to a mild disorder which only becomes evident in adulthood, manifesting as premature osteoporosis, .Most commonly, however, Osteogenesis imperfecta presents in childhood with multiple fractures and related complications, .The precise incidence of Osteogenesis imperfecta is unknown and reports vary from approximately 1/100,000 to 1/25,000 dependent on the criterion used to define Osteogenesis imperfecta.

Severe forms and milder disease occur with approximately similar incidence. Severe and mild forms share the cardinal feature of bone fragility, which is characterized by bone fractures often after little or no trauma, .Several findings in Osteogenesis imperfecta are common to other disorders of connective tissues; hyper-mobile joints and a blue sclera are among these features frequently described, The incorporation of abnormal type 1 collagen in teeth results in brittle opalescent teeth, the hallmark of Dentinogenesis Imperfecta, often seen in Osteogenesis imperfecta, .Progressive conductive hearing loss in early adulthood is the result of damage to the ossicles in the middle ear; over time, hearing loss typically progresses and combined conductive and sensorineural hearing loss may be seen in adults, similar to that of otosclerosis. Short stature and bone deformity are common features of the disorder The mainstay of treatment is orthopedic management along with physiotherapy, Bisphosphonates are being evaluated for efficacy and clinical trials have shown improvement at least in bone mineral density

Disorders associated with fragility fractures in children:

A) Primary conditions

  1. Genetic disorders :- Osteogenesis imperfecta - Ehlers-Danlos syndrome - Marfan syndrome Homocystinuria - Osteoporosis - Hypophosphatasia Polyostotic fibrous dysplasia - Rickets (genetic forms)
  2. Idiopathic juvenile osteoporosis B) Secondary conditions

1- Chronic inflammatory conditions Systemic lupus erythematosus - Inflammatory bowel disease - Nephrotic syndrome 2- Reduced mobility Cerebral palsy - Duchenne muscular dystrophy - Posttraumatic 3- Infiltrative Leukemia - Thalassemia

4- Endocrine Hypogonadism - Growth hormone deficiency - Cushing syndrome Hyperthyroidism - Diabetes mellitus 5- Nutritional/malabsorptive Vitamin D deficiency - Celiac disease - Biliary atresia Cystic fibrosis - Anorexia nervosa 6- Renal Chronic kidney disease - Secondary hyperparathyroidism 7- Iatrogenic Glucocorticoids - Anticonvulsants - Methotrexate - Radiation therapy

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Molecular Genetic Study of Suspected Cases of Osteogenesis Imperfecta Attending Assiut University Children Hospital
Estimated Study Start Date : June 1, 2017
Estimated Primary Completion Date : January 1, 2019
Estimated Study Completion Date : March 1, 2019

Group/Cohort Intervention/treatment
Repeated fractures group
detection of gene mutations of osteogenesis imperfecta in single group of patients with repeated fractures then start treatment with zoledronic acid in doses children less than 5 years ( 0.025 milligram for each kilogram every 3 months for 18 months duration) children more than 5 years ( 0.05 milligram for each kilogram every 6 months for 18 months duration)
Drug: Zoledronic Acid
intravenous injections once every 3 months

Primary Outcome Measures :
  1. Percentage of children diagnosed as osteogenesis imperfecta [ Time Frame: 1 month ]
    diagnosis based on molecular genetic study

Biospecimen Retention:   Samples With DNA
we collect blood samples of patients to detect COLLAGEN I AI gene and COLLAGEN 1 A2 gene

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Any Infants or children from age of 1 month up to age of 18 years presented with History of repeated fractures (more than one)

Inclusion Criteria:

  1. Positive family history of fractures or stillbirths.
  2. Results of biochemical tests correlate with osteogenesis imperfecta.
  3. Low bone density.

Exclusion Criteria:

  1. Presence of secondary causes of fractures.
  2. Abnormalities of biochemical tests or hormonal profile.
  3. Negative family history.
  4. Fractures in same site each time.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03169192

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Contact: Mohamed M El-tellawy, Professor (+20) 01003486595
Contact: Azza A El-tyeb, Professor (+20) 01006863271

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Assiut University
Assiut, Egypt, 71111
Sponsors and Collaborators
Assiut University
Publications of Results:
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Responsible Party: mohamed aboubakr mohamed, principal investigator, Assiut University Identifier: NCT03169192    
Other Study ID Numbers: OI
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: May 30, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bone Diseases
Osteogenesis Imperfecta
Bone Diseases, Metabolic
Metabolic Diseases
Musculoskeletal Diseases
Bone Diseases, Developmental
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases
Zoledronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs